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High Lp(a) tied to higher coronary plaque volume, progression
MANNHEIM, GERMANY – , an observational imaging study shows.
This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.
The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.
At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.
Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.
Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.
He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.
He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”
Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”
However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.
“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
Plaque burden
Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.
Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.
“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.
But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.
Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”
It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”
Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.
These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”
Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”
For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”
Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”
What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.
To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.
In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.
After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.
The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).
The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).
Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.
Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).
High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)
Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).
No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY – , an observational imaging study shows.
This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.
The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.
At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.
Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.
Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.
He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.
He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”
Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”
However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.
“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
Plaque burden
Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.
Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.
“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.
But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.
Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”
It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”
Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.
These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”
Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”
For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”
Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”
What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.
To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.
In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.
After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.
The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).
The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).
Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.
Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).
High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)
Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).
No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY – , an observational imaging study shows.
This could explain the greater risk for major adverse cardiovascular events seen in patients with high Lp(a) levels, suggests the research, presented during the annual European Atherosclerosis Society Congress.
The team performed follow-up coronary CT angiography (CCTA) on almost 275 patients who had undergone imaging approximately 10 years earlier, finding that almost one-third had high Lp(a) levels.
At baseline, per cent plaque volumes were 1.8 times greater in high Lp(a) patients versus those with low levels of the protein. After 10 years, plaque volumes were 3.3 times larger in patients with high Lp(a) levels.
Over this period, the rate of increase of plaque volume was 1.9 times greater in patients with high Lp(a) levels.
Study presenter Nick S. Nurmohamed, MD, PhD candidate, department of vascular medicine, Amsterdam University Medical Centers, also showed that high Lp(a) levels were associated with a 2.1-fold increase in rates of MACE.
He said in an interview that this finding could be related to Lp(a) increasing inflammatory signaling in the plaque, “making it more prone to rupture, and we saw that on the CCTA scans,” where high Lp(a) levels were associated with the presence of more high-risk plaques.
He added that in the absence of drugs that target Lp(a) levels directly, the results underline the need to focus on other means of lipid-lowering, as well as “creating awareness that Lp(a) is associated with plaque formation.”
Dr. Nurmohamed said that “for the moment, we have to treat patients with high Lp(a) with other risk-lowering therapies, such as low-density lipoprotein [LDL] cholesterol–lowering drugs, and the management of other risk factors.”
However, he noted that “there are a couple of Lp(a)-lowering medications in trials,” with results expected in the next 2-3 years.
“Then we will have the means to treat those patients, and with CCTA we can identify the patients with the biggest risk,” Dr. Nurmohamed added.
Plaque burden
Philippe Moulin, MD, PhD, head of endocrinology and professor of human nutrition at Faculté Lyon Est, Claude Bernard Lyon (France) 1 University, said that the association between Lp(a) and plaque burden has been seen previously in the literature in a very similar study but with only 1-year follow-up.
Similarly, registry data have suggested that Lp(a) is associated with worsening plaque progression over time.
“Here, with 10-year follow-up, [the study] is much more interesting,” due to its greater statistical power, he said in an interview. It is also “well-documented” and uses an “appropriate” methodology.
But Dr. Moulin underlined that the number of patients with high Lp(a) levels included in the study is relatively small.
Consequently, the researchers were not able to look at the level and rate of progression of atherosclerosis between different quartiles of Lp(a), “so you have no dose-response analysis.”
It also does not “establish causality,” as it remains an observational study, despite being longitudinal, “well done, and so on.”
Dr. Moulin added that the study nevertheless adds “one more stone” to the construct of the idea of high risk around high Lp(a) levels, and “prepares the ground” for the availability of two drugs to decrease Lp(a) levels, expected in 2026 and 2027.
These are expected to substantially reduce Lp(a) levels and achieve a reduction in cardiovascular risk of around 20%-40%, “which would be interesting,” especially as “we have patients who have Lp(a) levels four times above the upper normal value.”
Crucially, they may already have normal LDL cholesterol levels, meaning that, for some patients, “there is clearly a need for such treatment, as long as it is proven that it will decrease cardiovascular risk.”
For the moment, however, the strategy for managing patients with high Lp(a) remains to increase the dose of statin and to have more stringent targets, although Dr. Moulin pointed out that, “when you give statins, you raise slightly Lp(a) levels.”
Dr. Nurmohamed said in an interview that “we know from largely genetic and observational studies that Lp(a) is causally associated with atherosclerotic cardiovascular disease.”
What is less clear is the exact underlying mechanism, he said, noting that there have been several imaging studies in high and low Lp(a) patients that have yielded conflicting results in terms of the relationship with plaque burden.
To investigate the impact of Lp(a) levels on long-term coronary plaque progression, the team invited patients who had taken part in a previous CCTA study to undergo repeat CCTA, regardless of their underlying symptoms.
In all, 299 patients underwent follow-up imaging a median of 10.2 years after their original scan. Plaque volumes were quantified and adjusted for vessel volumes, and the patients were classified as having high (≥ 70 nmol/L) or low (< 70 nmol/L) Lp(a) levels.
After excluding patients who had undergone coronary artery bypass grafting, the team analyzed 274 patients with a mean age at baseline of 57 years. Of these, 159 (58%) were men. High Lp(a) levels were identified in 87 (32%) patients.
The team found that at baseline, patients with high Lp(a) levels had significantly larger percent atheroma volumes than those with low levels, at 3.92% versus 2.17%, or an absolute difference of 1.75% (P = .013).
The difference between the two groups was even greater at the follow-up, when percent atheroma volumes reached 8.75% in patients with high Lp(a) levels versus 3.90% for those with low levels, or an absolute difference of 4.85% (P = .005).
Similar findings were seen when looking separately at percentage of noncalcified and calcified plaque volumes as well as when analyzing for the presence of low-density plaques.
Multivariate analysis taking into account clinical risk factors, statin use, and CT tube voltage found that high Lp(a) levels were associated with a greater percent atheroma volume at baseline, at an odds ratio versus low Lp(a) of 1.83 (95% confidence interval, 0.12-3.54; P = .037).
High Lp(a) levels were also linked to a larger percent atheroma volume on follow-up imaging, at an odds ratio of 3.25 (95% CI, 0.80-5.71; P = .010), and a significantly greater change in atheroma volume from baseline to follow-up imaging, at an odds ratio of 1.86 (95% CI, 0.59-3.14; P = .005)
Finally, the team showed that, after adjusting for clinical risk factors, high baseline Lp(a) levels were associated with an increased risk of MACE during the follow-up period, at a hazard ratio versus low Lp(a) levels of 2.10 (95% CI, 1.01-4.29, P = .048).
No funding was declared. Dr. Nurmohamed is cofounder of Lipid Tools. Other authors declare relationships with Amgen, Novartis, Esperion, Sanofi-Regeneron, Ackee, Cleerly, GW Heart and Vascular Institute, Siemens Healthineers, and HeartFlow.
A version of this article first appeared on Medscape.com.
AT EAS 2023
Link between bipolar disorder and CVD mortality explained?
in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.
The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).
“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.
The study was published online in the Journal of Clinical Psychiatry.
‘Excessively present’
BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.
“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.
For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”
To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).
In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression.
Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.
Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
Positive affect beneficial?
Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).
After controlling for age, sex, and BMI (F3,202 = 4.47; P = .005; np2 = 0.06), the researchers found significant between-group differences in RHI.
Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.
RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).
The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.
“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.
There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.
They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”
Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
Observable changes in youth
In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.”
This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.
The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.
This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.
A version of this article first appeared on Medscape.com.
in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.
The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).
“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.
The study was published online in the Journal of Clinical Psychiatry.
‘Excessively present’
BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.
“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.
For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”
To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).
In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression.
Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.
Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
Positive affect beneficial?
Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).
After controlling for age, sex, and BMI (F3,202 = 4.47; P = .005; np2 = 0.06), the researchers found significant between-group differences in RHI.
Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.
RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).
The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.
“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.
There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.
They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”
Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
Observable changes in youth
In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.”
This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.
The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.
This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.
A version of this article first appeared on Medscape.com.
in new findings that may explain the “excessive and premature mortality” related to heart disease in this patient population.
The investigators found that higher reactive hyperemia index (RHI) scores, a measure of endothelial function, were tied to mood severity in patients with higher mania, but not depression scores. These findings persisted even after accounting for medications, obesity, and other cardiovascular risk factors (CVRFs).
“From a clinical perspective, these findings highlight the potential value of integrating vascular health in the assessment and management of youth with BD, and from a scientific perspective, these findings call for additional research focused on shared biological mechanisms linking vascular health and mood symptoms of BD,” senior investigator Benjamin Goldstein, MD, PhD, full professor of psychiatry, pharmacology, and psychological clinical science, University of Toronto, said in an interview.
The study was published online in the Journal of Clinical Psychiatry.
‘Excessively present’
BD is associated with “excessive and premature cardiovascular mortality” and CVD is “excessively present” in BD, exceeding what can be explained by traditional cardiovascular risk factors, psychiatric medications, and substance use, the researchers noted.
“In adults, more severe mood symptoms increase the risk of future CVD. Our focus on endothelial function rose due to the fact that CVD is rare in youth, whereas endothelial dysfunction – considered a precursor of CVD – can be assessed in youth,” said Dr. Goldstein, who holds the RBC Investments Chair in children’s mental health and developmental psychopathology at the Centre for Addiction and Mental Health, Toronto, where he is director of the Centre for Youth Bipolar Disorder.
For this reason, he and his colleagues were “interested in researching whether endothelial dysfunction is associated with mood symptoms in youth with BD.” Ultimately, the motivation was to “inspire new therapeutic opportunities that may improve both cardiovascular and mental health simultaneously.”
To investigate the question, the researchers studied 209 youth aged 13-20 years (n = 114 with BD and 94 healthy controls [HCs]).
In the BD group, there were 34 BD-euthymia, 36 BD-depressed, and 44 BD-hypomanic/mixed; and within the groups who had depression or hypomania/mixed features, 72 were experiencing clinically significant depression.
Participants had to be free of chronic inflammatory illness, use of medications that might be addressing traditional CVRFs, recent infectious diseases, or neurologic conditions.
Participants’ bipolar symptoms, psychosocial functioning, and family history were assessed. In addition, they were asked about treatment, physical and/or sexual abuse, smoking status, and socioeconomic status. Height, weight, waist circumference, blood pressure, and blood tests to assess CVRFs, including C-reactive protein (CRP), were also assessed. RHI was measured via pulse amplitude tonometry, with lower values indicating poorer endothelial function.
Positive affect beneficial?
Compared with HCs, there were fewer White participants in the BD group (78% vs. 55%; P < .001). The BD group also had higher Tanner stage development scores (stage 5: 65% vs. 35%; P = .03; V = 0.21), higher body mass index (BMI, 24.4 ± 4.6 vs. 22.0 ± 4.2; P < .001; d = 0.53), and higher CRP (1.94 ± 3.99 vs. 0.76 ± 0.86; P = .009; d = –0.40).
After controlling for age, sex, and BMI (F3,202 = 4.47; P = .005; np2 = 0.06), the researchers found significant between-group differences in RHI.
Post hoc pairwise comparisons showed RHI to be significantly lower in the BD-depressed versus the HC group (P = .04; d = 0.4). Moreover, the BD-hypomanic/mixed group had significantly higher RHI, compared with the other BD groups and the HC group.
RHI was associated with higher mania scores (beta, 0.26; P = .006), but there was no similar significant association with depression mood scores (beta, 0.01; P = .90).
The mood state differences in RHI and the RHI-mania association remained significant in sensitivity analyses examining the effect of current medication use as well as CVRFs, including lipids, CRP, and blood pressure on RHI.
“We found that youth with BD experiencing a depressive episode had lower endothelial function, whereas youth with BD experiencing a hypomanic/mixed episode had higher endothelial function, as compared to healthy youth,” Dr. Goldstein said.
There are several mechanisms potentially underlying the association between endothelial function and hypomania, the investigators noted. For example, positive affect is associated with increased endothelial function in normative samples, so hypomanic symptoms, including elation, may have similar beneficial associations, although those benefits likely do not extend to mania, which has been associated with cardiovascular risk.
They also point to several limitations in the study. The cross-sectional design “precludes making inferences regarding the temporal relationship between RHI and mood.” Moreover, the study focused only on hypomania, so “we cannot draw conclusions about mania.” In addition, the HC group had a “significantly higher proportion” of White participants, and a lower Tanner stage, so it “may not be a representative control sample.”
Nevertheless, the researchers concluded that the study “adds to the existing evidence for the potential value of integrating cardiovascular-related therapeutic approaches in BD,” noting that further research is needed to elucidate the mechanisms of the association.
Observable changes in youth
In a comment, Jess G Fiedorowicz, MD, PhD, head and chief, department of mental health, Ottawa Hospital Research Institute, noted that individuals with BD “have a much higher risk of CVD, which tends to develop earlier and shortens life expectancy by more than a decade.”
This cardiovascular risk “appears to be acquired over the long-term course of illness and proportionate to the persistence and severity of mood symptoms, which implies that mood syndromes, such as depression and mania, themselves may induce changes in the body relevant to CVD,” said Dr. Fiedorowicz, who is also a professor in the department of psychiatry and senior research chair in adult psychiatry at the Brain and Mind Research Institute, University of Ottawa, and was not involved with the study.
The study “adds to a growing body of evidence that mood syndromes may enact physiological changes that may be relevant to risk of CVD. One important aspect of this study is that this can even be observed in young sample,” he said.
This study was funded by the Canadian Institutes of Health Research and a Miner’s Lamp Innovation Fund from the University of Toronto. Dr. Goldstein and coauthors declare no relevant financial relationships. Dr. Fiedorowicz receives an honorarium from Elsevier for his work as editor-in-chief of the Journal of Psychosomatic Research.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL PSYCHIATRY
Three ‘synergistic’ problems when taking blood pressure
Insufficient blood pressure measurement during medical consultation, use of an inadequate technique for its determination, and lack of validated automatic sphygmomanometers are three problems that convergently complicate the diagnosis and control of arterial hypertension in the Americas, a silent disease that affects 180 million people in the region and is the main risk factor for cardiovascular diseases, said the Pan American Health Organization.
Jarbas Barbosa, MD, MPH, PhD, director of PAHO, said in an interview: “We don’t have specific data for each of these scenarios, but unfortunately, all three doubtless work together to make the situation worse.
“Often, the staff members at our primary care clinics are not prepared to diagnose and treat hypertension, because there aren’t national protocols to raise awareness and prepare them to provide this care to the correct standard. Also, they are often unqualified to take blood pressure readings properly,” he added.
This concern is reflected in the theme the organization chose for World Hypertension Day, which was observed on May 17: Measure your blood pressure accurately, control it, live longer! “We shouldn’t underestimate the importance of taking blood pressure,” warned Silvana Luciani, chief of PAHO’s noncommunicable diseases, violence, and injury prevention unit. But, the experts stressed, it must be done correctly.
Time no problem
It’s important to raise awareness of the value of blood pressure measurement for the general population. However, as multiple studies have shown, one barrier to detecting and controlling hypertension is that doctors and other health care professionals measure blood pressure less frequently in clinic than expected, or they use inappropriate techniques or obsolete or uncalibrated measurement devices.
“The importance of clinic blood pressure measurement has been recognized for many decades, but adherence to guidelines on proper, standardized blood pressure measurement remains uncommon in clinical practice,” concluded a consensus document signed by 25 experts from 13 institutions in the United States, Australia, Germany, the United Kingdom, Canada, Italy, Belgium, and Greece.
The first problem lies in the low quantity of measurements. A recent study in Argentina of nearly 3,000 visits to the doctor’s office at nine health care centers showed that doctors took blood pressure readings in only once in every seven encounters. Even cardiologists, the specialists with the best performance, did so only half of the time.
“Several factors can come into play: lack of awareness, medical inertia, or lack of appropriate equipment. But it is not for lack of time. How long does it take to take blood pressure three times within a 1-minute interval, with the patient seated and their back supported, as indicated? Four minutes. That’s not very much,” said Judith Zilberman, MD, PhD, said in an interview. Dr. Zilberman leads the department of hypertension and the women’s cardiovascular disease area at the Argerich Hospital in Buenos Aires, and is the former chair of the Argentinian Society of Hypertension.
Patricio López-Jaramillo, MD, PhD, said in an interview that the greatest obstacle is the lack of awareness among physicians and other health care staff about the importance of taking proper blood pressure measurements. Dr. López-Jaramillo is president and scientific director of the MASIRA Research Institute at the University of Santander in Bucaramanga, Colombia, and first author of the Manual Práctico de Diagnóstico y Manejo de la Hipertensión Arterial (Practice Guidelines for Diagnosing and Managing Hypertension), published by the Latin American Hypertension Society.
“Medical schools are also responsible for this. They go over this topic very superficially during undergraduate and, even worse, postgraduate training. The lack of time to take correct measurements, or the lack of appropriate instruments, is secondary to this lack of awareness among most health care staff members,” added Dr. López-Jaramillo, who is one of the researchers of the PURE epidemiologic study. Since 2002, it has followed a cohort of 225,000 participants from 27 high-, mid-, and low-income countries.
Dr. Zilberman added that it would be good practice for all primary care physicians to take blood pressure readings regardless of the reason for the visit and whether patients have been diagnosed with hypertension or not. “If a woman goes to her gynecologist because she wants to get pregnant, her blood pressure should also be taken! And any other specialist should interview the patient, ascertain her history, what medications she’s on, and then ask if her blood pressure has been taken recently,” she recommended.
Measure well
The second factor to consider is that a correct technique should be used to take blood pressure readings in the doctor’s office or clinic so as not to produce inaccurate results that could lead to underdiagnosis, overdiagnosis, or a poor assessment of the patient’s response to prescribed treatments. An observational study performed in Uruguay in 2017 showed that only 5% of 302 blood pressure measurements followed appropriate procedures.
A new fact sheet from the PAHO lists the following eight requirements for obtaining an accurate reading: don’t have a conversation, support the arm at heart level, put the cuff on a bare arm, use the correct cuff size, support the feet, keep the legs uncrossed, ensure the patient has an empty bladder, and support the back.
Though most guidelines recommend taking three readings, the “pragmatic” focus proposed in the international consensus accepts at least two readings separated by a minimum of 30 seconds. The two readings should then be averaged out. There is evidence that simplified protocols can be used, at least for population screening.
The authors of the new document also recommend preparing the patient before taking the measurement. The patient should be asked not to smoke, exercise, or consume alcohol or caffeine for at least 30 minutes beforehand. He or she should rest for a period of 3-5 minutes without speaking or being spoken to before the measurement is taken.
Lastly, clinically validated automated measurement devices should be used, as called for by the PAHO HEARTS initiative in the Americas. “The sphygmomanometer or classic aneroid tensiometer for the auscultatory method, which is still used way too often at doctor’s office visits in the region, has many weaknesses – not only the device itself but also the way it’s used (human error). This produces a rounded, approximate reading,” stressed Dr. Zilberman.
Automated devices also minimize interactions with the patient by reducing distractions during the preparation and measurement phases and freeing up time for the health care professional. “To [check for a] fever, we use the appropriate thermometer in the appropriate location. We should do the same for blood pressure,” she added.
The STRIDE-BP database, which is affiliated with the European Society of Hypertension, the International Society of Hypertension, and the World Hypertension League, contains an updated list of validated devices for measuring blood pressure.
The signers of the consensus likewise recognized that, beyond taking blood pressure measurements during office visits, the best measurements are those taken at home outside the context of medical care (doctor’s office or clinic) and that the same recommendations are directly applicable. “Few diseases can be detected so easily as with a simple at-home assessment performed by the individual himself or herself. If after three consecutive measurements, readings above 140/90 mm Hg are obtained, the individual should see the doctor to set up a comprehensive treatment program,” said Pablo Rodríguez, MD, secretary of the Argentinian Society of Hypertension. From now through September 14 (Day for Patients With Hypertension), the society is conducting a campaign to take blood pressure measurements at different locations across the country.
Dr. Zilberman and Dr. López-Jiménez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
Insufficient blood pressure measurement during medical consultation, use of an inadequate technique for its determination, and lack of validated automatic sphygmomanometers are three problems that convergently complicate the diagnosis and control of arterial hypertension in the Americas, a silent disease that affects 180 million people in the region and is the main risk factor for cardiovascular diseases, said the Pan American Health Organization.
Jarbas Barbosa, MD, MPH, PhD, director of PAHO, said in an interview: “We don’t have specific data for each of these scenarios, but unfortunately, all three doubtless work together to make the situation worse.
“Often, the staff members at our primary care clinics are not prepared to diagnose and treat hypertension, because there aren’t national protocols to raise awareness and prepare them to provide this care to the correct standard. Also, they are often unqualified to take blood pressure readings properly,” he added.
This concern is reflected in the theme the organization chose for World Hypertension Day, which was observed on May 17: Measure your blood pressure accurately, control it, live longer! “We shouldn’t underestimate the importance of taking blood pressure,” warned Silvana Luciani, chief of PAHO’s noncommunicable diseases, violence, and injury prevention unit. But, the experts stressed, it must be done correctly.
Time no problem
It’s important to raise awareness of the value of blood pressure measurement for the general population. However, as multiple studies have shown, one barrier to detecting and controlling hypertension is that doctors and other health care professionals measure blood pressure less frequently in clinic than expected, or they use inappropriate techniques or obsolete or uncalibrated measurement devices.
“The importance of clinic blood pressure measurement has been recognized for many decades, but adherence to guidelines on proper, standardized blood pressure measurement remains uncommon in clinical practice,” concluded a consensus document signed by 25 experts from 13 institutions in the United States, Australia, Germany, the United Kingdom, Canada, Italy, Belgium, and Greece.
The first problem lies in the low quantity of measurements. A recent study in Argentina of nearly 3,000 visits to the doctor’s office at nine health care centers showed that doctors took blood pressure readings in only once in every seven encounters. Even cardiologists, the specialists with the best performance, did so only half of the time.
“Several factors can come into play: lack of awareness, medical inertia, or lack of appropriate equipment. But it is not for lack of time. How long does it take to take blood pressure three times within a 1-minute interval, with the patient seated and their back supported, as indicated? Four minutes. That’s not very much,” said Judith Zilberman, MD, PhD, said in an interview. Dr. Zilberman leads the department of hypertension and the women’s cardiovascular disease area at the Argerich Hospital in Buenos Aires, and is the former chair of the Argentinian Society of Hypertension.
Patricio López-Jaramillo, MD, PhD, said in an interview that the greatest obstacle is the lack of awareness among physicians and other health care staff about the importance of taking proper blood pressure measurements. Dr. López-Jaramillo is president and scientific director of the MASIRA Research Institute at the University of Santander in Bucaramanga, Colombia, and first author of the Manual Práctico de Diagnóstico y Manejo de la Hipertensión Arterial (Practice Guidelines for Diagnosing and Managing Hypertension), published by the Latin American Hypertension Society.
“Medical schools are also responsible for this. They go over this topic very superficially during undergraduate and, even worse, postgraduate training. The lack of time to take correct measurements, or the lack of appropriate instruments, is secondary to this lack of awareness among most health care staff members,” added Dr. López-Jaramillo, who is one of the researchers of the PURE epidemiologic study. Since 2002, it has followed a cohort of 225,000 participants from 27 high-, mid-, and low-income countries.
Dr. Zilberman added that it would be good practice for all primary care physicians to take blood pressure readings regardless of the reason for the visit and whether patients have been diagnosed with hypertension or not. “If a woman goes to her gynecologist because she wants to get pregnant, her blood pressure should also be taken! And any other specialist should interview the patient, ascertain her history, what medications she’s on, and then ask if her blood pressure has been taken recently,” she recommended.
Measure well
The second factor to consider is that a correct technique should be used to take blood pressure readings in the doctor’s office or clinic so as not to produce inaccurate results that could lead to underdiagnosis, overdiagnosis, or a poor assessment of the patient’s response to prescribed treatments. An observational study performed in Uruguay in 2017 showed that only 5% of 302 blood pressure measurements followed appropriate procedures.
A new fact sheet from the PAHO lists the following eight requirements for obtaining an accurate reading: don’t have a conversation, support the arm at heart level, put the cuff on a bare arm, use the correct cuff size, support the feet, keep the legs uncrossed, ensure the patient has an empty bladder, and support the back.
Though most guidelines recommend taking three readings, the “pragmatic” focus proposed in the international consensus accepts at least two readings separated by a minimum of 30 seconds. The two readings should then be averaged out. There is evidence that simplified protocols can be used, at least for population screening.
The authors of the new document also recommend preparing the patient before taking the measurement. The patient should be asked not to smoke, exercise, or consume alcohol or caffeine for at least 30 minutes beforehand. He or she should rest for a period of 3-5 minutes without speaking or being spoken to before the measurement is taken.
Lastly, clinically validated automated measurement devices should be used, as called for by the PAHO HEARTS initiative in the Americas. “The sphygmomanometer or classic aneroid tensiometer for the auscultatory method, which is still used way too often at doctor’s office visits in the region, has many weaknesses – not only the device itself but also the way it’s used (human error). This produces a rounded, approximate reading,” stressed Dr. Zilberman.
Automated devices also minimize interactions with the patient by reducing distractions during the preparation and measurement phases and freeing up time for the health care professional. “To [check for a] fever, we use the appropriate thermometer in the appropriate location. We should do the same for blood pressure,” she added.
The STRIDE-BP database, which is affiliated with the European Society of Hypertension, the International Society of Hypertension, and the World Hypertension League, contains an updated list of validated devices for measuring blood pressure.
The signers of the consensus likewise recognized that, beyond taking blood pressure measurements during office visits, the best measurements are those taken at home outside the context of medical care (doctor’s office or clinic) and that the same recommendations are directly applicable. “Few diseases can be detected so easily as with a simple at-home assessment performed by the individual himself or herself. If after three consecutive measurements, readings above 140/90 mm Hg are obtained, the individual should see the doctor to set up a comprehensive treatment program,” said Pablo Rodríguez, MD, secretary of the Argentinian Society of Hypertension. From now through September 14 (Day for Patients With Hypertension), the society is conducting a campaign to take blood pressure measurements at different locations across the country.
Dr. Zilberman and Dr. López-Jiménez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
Insufficient blood pressure measurement during medical consultation, use of an inadequate technique for its determination, and lack of validated automatic sphygmomanometers are three problems that convergently complicate the diagnosis and control of arterial hypertension in the Americas, a silent disease that affects 180 million people in the region and is the main risk factor for cardiovascular diseases, said the Pan American Health Organization.
Jarbas Barbosa, MD, MPH, PhD, director of PAHO, said in an interview: “We don’t have specific data for each of these scenarios, but unfortunately, all three doubtless work together to make the situation worse.
“Often, the staff members at our primary care clinics are not prepared to diagnose and treat hypertension, because there aren’t national protocols to raise awareness and prepare them to provide this care to the correct standard. Also, they are often unqualified to take blood pressure readings properly,” he added.
This concern is reflected in the theme the organization chose for World Hypertension Day, which was observed on May 17: Measure your blood pressure accurately, control it, live longer! “We shouldn’t underestimate the importance of taking blood pressure,” warned Silvana Luciani, chief of PAHO’s noncommunicable diseases, violence, and injury prevention unit. But, the experts stressed, it must be done correctly.
Time no problem
It’s important to raise awareness of the value of blood pressure measurement for the general population. However, as multiple studies have shown, one barrier to detecting and controlling hypertension is that doctors and other health care professionals measure blood pressure less frequently in clinic than expected, or they use inappropriate techniques or obsolete or uncalibrated measurement devices.
“The importance of clinic blood pressure measurement has been recognized for many decades, but adherence to guidelines on proper, standardized blood pressure measurement remains uncommon in clinical practice,” concluded a consensus document signed by 25 experts from 13 institutions in the United States, Australia, Germany, the United Kingdom, Canada, Italy, Belgium, and Greece.
The first problem lies in the low quantity of measurements. A recent study in Argentina of nearly 3,000 visits to the doctor’s office at nine health care centers showed that doctors took blood pressure readings in only once in every seven encounters. Even cardiologists, the specialists with the best performance, did so only half of the time.
“Several factors can come into play: lack of awareness, medical inertia, or lack of appropriate equipment. But it is not for lack of time. How long does it take to take blood pressure three times within a 1-minute interval, with the patient seated and their back supported, as indicated? Four minutes. That’s not very much,” said Judith Zilberman, MD, PhD, said in an interview. Dr. Zilberman leads the department of hypertension and the women’s cardiovascular disease area at the Argerich Hospital in Buenos Aires, and is the former chair of the Argentinian Society of Hypertension.
Patricio López-Jaramillo, MD, PhD, said in an interview that the greatest obstacle is the lack of awareness among physicians and other health care staff about the importance of taking proper blood pressure measurements. Dr. López-Jaramillo is president and scientific director of the MASIRA Research Institute at the University of Santander in Bucaramanga, Colombia, and first author of the Manual Práctico de Diagnóstico y Manejo de la Hipertensión Arterial (Practice Guidelines for Diagnosing and Managing Hypertension), published by the Latin American Hypertension Society.
“Medical schools are also responsible for this. They go over this topic very superficially during undergraduate and, even worse, postgraduate training. The lack of time to take correct measurements, or the lack of appropriate instruments, is secondary to this lack of awareness among most health care staff members,” added Dr. López-Jaramillo, who is one of the researchers of the PURE epidemiologic study. Since 2002, it has followed a cohort of 225,000 participants from 27 high-, mid-, and low-income countries.
Dr. Zilberman added that it would be good practice for all primary care physicians to take blood pressure readings regardless of the reason for the visit and whether patients have been diagnosed with hypertension or not. “If a woman goes to her gynecologist because she wants to get pregnant, her blood pressure should also be taken! And any other specialist should interview the patient, ascertain her history, what medications she’s on, and then ask if her blood pressure has been taken recently,” she recommended.
Measure well
The second factor to consider is that a correct technique should be used to take blood pressure readings in the doctor’s office or clinic so as not to produce inaccurate results that could lead to underdiagnosis, overdiagnosis, or a poor assessment of the patient’s response to prescribed treatments. An observational study performed in Uruguay in 2017 showed that only 5% of 302 blood pressure measurements followed appropriate procedures.
A new fact sheet from the PAHO lists the following eight requirements for obtaining an accurate reading: don’t have a conversation, support the arm at heart level, put the cuff on a bare arm, use the correct cuff size, support the feet, keep the legs uncrossed, ensure the patient has an empty bladder, and support the back.
Though most guidelines recommend taking three readings, the “pragmatic” focus proposed in the international consensus accepts at least two readings separated by a minimum of 30 seconds. The two readings should then be averaged out. There is evidence that simplified protocols can be used, at least for population screening.
The authors of the new document also recommend preparing the patient before taking the measurement. The patient should be asked not to smoke, exercise, or consume alcohol or caffeine for at least 30 minutes beforehand. He or she should rest for a period of 3-5 minutes without speaking or being spoken to before the measurement is taken.
Lastly, clinically validated automated measurement devices should be used, as called for by the PAHO HEARTS initiative in the Americas. “The sphygmomanometer or classic aneroid tensiometer for the auscultatory method, which is still used way too often at doctor’s office visits in the region, has many weaknesses – not only the device itself but also the way it’s used (human error). This produces a rounded, approximate reading,” stressed Dr. Zilberman.
Automated devices also minimize interactions with the patient by reducing distractions during the preparation and measurement phases and freeing up time for the health care professional. “To [check for a] fever, we use the appropriate thermometer in the appropriate location. We should do the same for blood pressure,” she added.
The STRIDE-BP database, which is affiliated with the European Society of Hypertension, the International Society of Hypertension, and the World Hypertension League, contains an updated list of validated devices for measuring blood pressure.
The signers of the consensus likewise recognized that, beyond taking blood pressure measurements during office visits, the best measurements are those taken at home outside the context of medical care (doctor’s office or clinic) and that the same recommendations are directly applicable. “Few diseases can be detected so easily as with a simple at-home assessment performed by the individual himself or herself. If after three consecutive measurements, readings above 140/90 mm Hg are obtained, the individual should see the doctor to set up a comprehensive treatment program,” said Pablo Rodríguez, MD, secretary of the Argentinian Society of Hypertension. From now through September 14 (Day for Patients With Hypertension), the society is conducting a campaign to take blood pressure measurements at different locations across the country.
Dr. Zilberman and Dr. López-Jiménez disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish Edition. A version appeared on Medscape.com.
Medicaid patients with heart failure get poor follow-up after hospital discharge
Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.
In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.
The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.
Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.
Study details
The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.
The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.
Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.
In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
Ethnic/gender/age disparities
Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.
Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.
Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.
In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.
The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.
Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.
Study details
The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.
The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.
Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.
In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
Ethnic/gender/age disparities
Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.
Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.
Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.
In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.
The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.
Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.
Study details
The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.
The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.
Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.
In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
Ethnic/gender/age disparities
Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.
Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.
FROM JOURNAL OF THE AMERICAN HEART ASSOCIATION
Lomitapide shows promise in pediatric homozygous FH
MANNHEIM, Germany – Lomitapide, which reduces lipoprotein production in the liver, could help manage pediatric homozygous familial hypercholesterolemia (HoFH), suggest results of a trial that showed large reductions in circulating lipids.
The research was presented May 23 at the 91st European Atherosclerosis Society Congress.
Lomitapide inhibits microsomal triglyceride transfer protein, which plays a key role in apolipoprotein B-containing lipoprotein assembly and secretion in the liver and intestines. Crucially, the drug acts independently of the LDL cholesterol receptor.
It was approved in December 2012 by the U.S. Food and Drug Administration for use in adults with HoFH, sold under the name Juxtapid, and by the European Medicines Agency, where the brand name is Lojuxta.
The current trial involved more than 40 children and teenagers with HoFH aged 5-17 years; they were treated with the drug for 24 weeks, resulting in reductions of low density lipoprotein cholesterol of almost 54%, with nearly 42% reaching target levels.
The drug was also associated with marked reductions in other key lipids of at least 50%. However, 67% of patients also experienced gastrointestinal adverse events, and around 25% saw their levels of liver enzymes increase.
Early diagnosis ‘imperative’
The findings show that the “early diagnosis and treatment of HoFH is imperative,” said study presenter Luis Masana, MD, PhD, director of the Vascular Medicine and Metabolism Unit at Sant Joan de Reus University Hospital, Tarragona, Spain.
“I think that, with these results, we are bringing a new hope for this group of patients,” he continued. “I also think we will increase the quality of life, not just of the patients but also all the families involved in [managing] this problem.”
Session co-chair Andreas Zirlik, MD, PhD, head of the department of cardiology and chairman of the University Heart Center Graz, LKH-University Hospital, and Medical University of Graz (Austria), was more circumspect in his appraisal of the results.
He told this news organization that it is “always very difficult to establish therapy in pediatrics,” and believes that the drug “will give us an additional option” in managing HoFH.
However, Dr. Zirlik warned that he is a “little bit concerned” about lomitapide’s adverse event profile, and “would need to see a little bit deeper into the safety data.”
Highlighting the elevations in liver enzymes of around 25%, he asked: “What does it mean?” And how will it “play out in the long run?”
Beyond lomitapide, Dr. Zirlik pointed out that there are other drugs that have shown potential in managing HoFH and could potentially be used in the pediatric population, such as angiopoietin-like 3 protein (ANGPTL3) inhibitors and small interfering RNA (siRNA) compounds that target upstream production. “So, let’s see how they pan out,” he said.
Life-limiting condition
HoFH is an “ultra-rare, life-limiting condition,” with an estimated prevalence of approximately 3 per 1 million people, and a life expectancy in untreated patients of just 18 years, Dr. Masana said during his presentation.
Case series of lomitapide use in pediatric HoFH patients have shown encouraging results that are consistent with those seen in adults, he noted, with many able to achieve their LDL cholesterol target and stop or reduce apheresis.
To investigate further, a phase 3, single arm, open-label study was conducted. Following screening, 46 children and teenagers with HoFH underwent a 6- to 12-week run-in period, during which they were put on a low-fat diet with nutritional supplements.
“As you can imagine,” Dr. Masana said, “we are reducing the capacity for fat absorption with lomitapide, so the supplements and low-fat diet are necessary.”
Of these, 43 participants then entered a 24-week treatment period in which they were started on one of three doses, before undergoing dose escalation to the maximally tolerated dose. This was followed by an 80-week open-label safety phase, in which they continued on the maximally tolerated dose, then a follow-up period.
For the current presentation, Dr. Masana focused on the efficacy phase, showing that the mean age of participants was 10.7 years and that 55.8% were female. The HoFH diagnosis was confirmed genetically in 88.4% of cases.
Results showed that lomitapide was associated with a significant reduction in LDL cholesterol levels, from 435.8 mg/dL at baseline to 176.5 mg/dL at Week 24, which corresponded to a 53.5% overall reduction (P < .0001).
This meant that 41.9% of patients achieved their EAS LDL cholesterol target of less than 135 mg/dL at some point during the 24-week treatment period.
Stratifying by age, the reduction between baseline and week 24 was 538.5 mg/dL to 207.2 mg/dL, or 56.5%, in the 20 children aged 5-10 years, and 346.5 mg/dL to 149.9 mg/L, or 50.9%, in the 23 patients aged 11-17 years.
Dr. Masana explained that the results were “a little bit better in the younger group because they were receiving less treatment at this stage of the disease” than the older group.
He showed that lomitapide was associated with significant reductions in other lipid markers, including a 53.9% reduction in non–HDL cholesterol (P < .0001), a 50.1% drop in total cholesterol (P < .0001), and a 50.2% fall in very-low-density lipoprotein cholesterol (P < .0001).
Results showed 93% of patients experienced treatment-related adverse events, with 11.6% having serious events and 4.7% having events that led to study discontinuation. There was one (2.3%) major adverse cardiac event but no deaths.
He said that, despite these figures, the adverse events were “mostly mild or moderate.”
The majority (67%) of patients nevertheless had gastrointestinal adverse events, which were, “in general, associated with a lack of adherence to the low-fat diet.”
Aspartate aminotransferase levels were elevated in 23% of patients, while 28% had elevations in alanine aminotransferase, which were described by Dr. Masana as “moderate.”
The study was sponsored by Amryt Pharma. Dr. Masana declares relationships with Amarin, Amryt, Daiichi-Sankyo, Novartis, Sanofi, Servier, Servier, and Viatrix.
A version of this article first appeared on Medscape.com.
MANNHEIM, Germany – Lomitapide, which reduces lipoprotein production in the liver, could help manage pediatric homozygous familial hypercholesterolemia (HoFH), suggest results of a trial that showed large reductions in circulating lipids.
The research was presented May 23 at the 91st European Atherosclerosis Society Congress.
Lomitapide inhibits microsomal triglyceride transfer protein, which plays a key role in apolipoprotein B-containing lipoprotein assembly and secretion in the liver and intestines. Crucially, the drug acts independently of the LDL cholesterol receptor.
It was approved in December 2012 by the U.S. Food and Drug Administration for use in adults with HoFH, sold under the name Juxtapid, and by the European Medicines Agency, where the brand name is Lojuxta.
The current trial involved more than 40 children and teenagers with HoFH aged 5-17 years; they were treated with the drug for 24 weeks, resulting in reductions of low density lipoprotein cholesterol of almost 54%, with nearly 42% reaching target levels.
The drug was also associated with marked reductions in other key lipids of at least 50%. However, 67% of patients also experienced gastrointestinal adverse events, and around 25% saw their levels of liver enzymes increase.
Early diagnosis ‘imperative’
The findings show that the “early diagnosis and treatment of HoFH is imperative,” said study presenter Luis Masana, MD, PhD, director of the Vascular Medicine and Metabolism Unit at Sant Joan de Reus University Hospital, Tarragona, Spain.
“I think that, with these results, we are bringing a new hope for this group of patients,” he continued. “I also think we will increase the quality of life, not just of the patients but also all the families involved in [managing] this problem.”
Session co-chair Andreas Zirlik, MD, PhD, head of the department of cardiology and chairman of the University Heart Center Graz, LKH-University Hospital, and Medical University of Graz (Austria), was more circumspect in his appraisal of the results.
He told this news organization that it is “always very difficult to establish therapy in pediatrics,” and believes that the drug “will give us an additional option” in managing HoFH.
However, Dr. Zirlik warned that he is a “little bit concerned” about lomitapide’s adverse event profile, and “would need to see a little bit deeper into the safety data.”
Highlighting the elevations in liver enzymes of around 25%, he asked: “What does it mean?” And how will it “play out in the long run?”
Beyond lomitapide, Dr. Zirlik pointed out that there are other drugs that have shown potential in managing HoFH and could potentially be used in the pediatric population, such as angiopoietin-like 3 protein (ANGPTL3) inhibitors and small interfering RNA (siRNA) compounds that target upstream production. “So, let’s see how they pan out,” he said.
Life-limiting condition
HoFH is an “ultra-rare, life-limiting condition,” with an estimated prevalence of approximately 3 per 1 million people, and a life expectancy in untreated patients of just 18 years, Dr. Masana said during his presentation.
Case series of lomitapide use in pediatric HoFH patients have shown encouraging results that are consistent with those seen in adults, he noted, with many able to achieve their LDL cholesterol target and stop or reduce apheresis.
To investigate further, a phase 3, single arm, open-label study was conducted. Following screening, 46 children and teenagers with HoFH underwent a 6- to 12-week run-in period, during which they were put on a low-fat diet with nutritional supplements.
“As you can imagine,” Dr. Masana said, “we are reducing the capacity for fat absorption with lomitapide, so the supplements and low-fat diet are necessary.”
Of these, 43 participants then entered a 24-week treatment period in which they were started on one of three doses, before undergoing dose escalation to the maximally tolerated dose. This was followed by an 80-week open-label safety phase, in which they continued on the maximally tolerated dose, then a follow-up period.
For the current presentation, Dr. Masana focused on the efficacy phase, showing that the mean age of participants was 10.7 years and that 55.8% were female. The HoFH diagnosis was confirmed genetically in 88.4% of cases.
Results showed that lomitapide was associated with a significant reduction in LDL cholesterol levels, from 435.8 mg/dL at baseline to 176.5 mg/dL at Week 24, which corresponded to a 53.5% overall reduction (P < .0001).
This meant that 41.9% of patients achieved their EAS LDL cholesterol target of less than 135 mg/dL at some point during the 24-week treatment period.
Stratifying by age, the reduction between baseline and week 24 was 538.5 mg/dL to 207.2 mg/dL, or 56.5%, in the 20 children aged 5-10 years, and 346.5 mg/dL to 149.9 mg/L, or 50.9%, in the 23 patients aged 11-17 years.
Dr. Masana explained that the results were “a little bit better in the younger group because they were receiving less treatment at this stage of the disease” than the older group.
He showed that lomitapide was associated with significant reductions in other lipid markers, including a 53.9% reduction in non–HDL cholesterol (P < .0001), a 50.1% drop in total cholesterol (P < .0001), and a 50.2% fall in very-low-density lipoprotein cholesterol (P < .0001).
Results showed 93% of patients experienced treatment-related adverse events, with 11.6% having serious events and 4.7% having events that led to study discontinuation. There was one (2.3%) major adverse cardiac event but no deaths.
He said that, despite these figures, the adverse events were “mostly mild or moderate.”
The majority (67%) of patients nevertheless had gastrointestinal adverse events, which were, “in general, associated with a lack of adherence to the low-fat diet.”
Aspartate aminotransferase levels were elevated in 23% of patients, while 28% had elevations in alanine aminotransferase, which were described by Dr. Masana as “moderate.”
The study was sponsored by Amryt Pharma. Dr. Masana declares relationships with Amarin, Amryt, Daiichi-Sankyo, Novartis, Sanofi, Servier, Servier, and Viatrix.
A version of this article first appeared on Medscape.com.
MANNHEIM, Germany – Lomitapide, which reduces lipoprotein production in the liver, could help manage pediatric homozygous familial hypercholesterolemia (HoFH), suggest results of a trial that showed large reductions in circulating lipids.
The research was presented May 23 at the 91st European Atherosclerosis Society Congress.
Lomitapide inhibits microsomal triglyceride transfer protein, which plays a key role in apolipoprotein B-containing lipoprotein assembly and secretion in the liver and intestines. Crucially, the drug acts independently of the LDL cholesterol receptor.
It was approved in December 2012 by the U.S. Food and Drug Administration for use in adults with HoFH, sold under the name Juxtapid, and by the European Medicines Agency, where the brand name is Lojuxta.
The current trial involved more than 40 children and teenagers with HoFH aged 5-17 years; they were treated with the drug for 24 weeks, resulting in reductions of low density lipoprotein cholesterol of almost 54%, with nearly 42% reaching target levels.
The drug was also associated with marked reductions in other key lipids of at least 50%. However, 67% of patients also experienced gastrointestinal adverse events, and around 25% saw their levels of liver enzymes increase.
Early diagnosis ‘imperative’
The findings show that the “early diagnosis and treatment of HoFH is imperative,” said study presenter Luis Masana, MD, PhD, director of the Vascular Medicine and Metabolism Unit at Sant Joan de Reus University Hospital, Tarragona, Spain.
“I think that, with these results, we are bringing a new hope for this group of patients,” he continued. “I also think we will increase the quality of life, not just of the patients but also all the families involved in [managing] this problem.”
Session co-chair Andreas Zirlik, MD, PhD, head of the department of cardiology and chairman of the University Heart Center Graz, LKH-University Hospital, and Medical University of Graz (Austria), was more circumspect in his appraisal of the results.
He told this news organization that it is “always very difficult to establish therapy in pediatrics,” and believes that the drug “will give us an additional option” in managing HoFH.
However, Dr. Zirlik warned that he is a “little bit concerned” about lomitapide’s adverse event profile, and “would need to see a little bit deeper into the safety data.”
Highlighting the elevations in liver enzymes of around 25%, he asked: “What does it mean?” And how will it “play out in the long run?”
Beyond lomitapide, Dr. Zirlik pointed out that there are other drugs that have shown potential in managing HoFH and could potentially be used in the pediatric population, such as angiopoietin-like 3 protein (ANGPTL3) inhibitors and small interfering RNA (siRNA) compounds that target upstream production. “So, let’s see how they pan out,” he said.
Life-limiting condition
HoFH is an “ultra-rare, life-limiting condition,” with an estimated prevalence of approximately 3 per 1 million people, and a life expectancy in untreated patients of just 18 years, Dr. Masana said during his presentation.
Case series of lomitapide use in pediatric HoFH patients have shown encouraging results that are consistent with those seen in adults, he noted, with many able to achieve their LDL cholesterol target and stop or reduce apheresis.
To investigate further, a phase 3, single arm, open-label study was conducted. Following screening, 46 children and teenagers with HoFH underwent a 6- to 12-week run-in period, during which they were put on a low-fat diet with nutritional supplements.
“As you can imagine,” Dr. Masana said, “we are reducing the capacity for fat absorption with lomitapide, so the supplements and low-fat diet are necessary.”
Of these, 43 participants then entered a 24-week treatment period in which they were started on one of three doses, before undergoing dose escalation to the maximally tolerated dose. This was followed by an 80-week open-label safety phase, in which they continued on the maximally tolerated dose, then a follow-up period.
For the current presentation, Dr. Masana focused on the efficacy phase, showing that the mean age of participants was 10.7 years and that 55.8% were female. The HoFH diagnosis was confirmed genetically in 88.4% of cases.
Results showed that lomitapide was associated with a significant reduction in LDL cholesterol levels, from 435.8 mg/dL at baseline to 176.5 mg/dL at Week 24, which corresponded to a 53.5% overall reduction (P < .0001).
This meant that 41.9% of patients achieved their EAS LDL cholesterol target of less than 135 mg/dL at some point during the 24-week treatment period.
Stratifying by age, the reduction between baseline and week 24 was 538.5 mg/dL to 207.2 mg/dL, or 56.5%, in the 20 children aged 5-10 years, and 346.5 mg/dL to 149.9 mg/L, or 50.9%, in the 23 patients aged 11-17 years.
Dr. Masana explained that the results were “a little bit better in the younger group because they were receiving less treatment at this stage of the disease” than the older group.
He showed that lomitapide was associated with significant reductions in other lipid markers, including a 53.9% reduction in non–HDL cholesterol (P < .0001), a 50.1% drop in total cholesterol (P < .0001), and a 50.2% fall in very-low-density lipoprotein cholesterol (P < .0001).
Results showed 93% of patients experienced treatment-related adverse events, with 11.6% having serious events and 4.7% having events that led to study discontinuation. There was one (2.3%) major adverse cardiac event but no deaths.
He said that, despite these figures, the adverse events were “mostly mild or moderate.”
The majority (67%) of patients nevertheless had gastrointestinal adverse events, which were, “in general, associated with a lack of adherence to the low-fat diet.”
Aspartate aminotransferase levels were elevated in 23% of patients, while 28% had elevations in alanine aminotransferase, which were described by Dr. Masana as “moderate.”
The study was sponsored by Amryt Pharma. Dr. Masana declares relationships with Amarin, Amryt, Daiichi-Sankyo, Novartis, Sanofi, Servier, Servier, and Viatrix.
A version of this article first appeared on Medscape.com.
Troponin to ID diabetes patients with silent heart disease?
– based on data from a representative sample of more than 10,000 U.S. adults.
The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.
The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.
“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.
“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”
“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
Need for aggressive CVD risk reduction
The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.
“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”
However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.
“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.
“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.
Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
ADA report already recommends testing these biomarkers for HF
However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.
“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.
The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.
“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.
All study participants had recorded measures of hs-cTnT and NT-proBNP.
The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.
The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.
“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
Diabetes linked with a doubled prevalence of elevated hs-cTnT
After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.
“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”
In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.
Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.
However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.
The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.
The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.
A version of this article first appeared on Medscape.com.
– based on data from a representative sample of more than 10,000 U.S. adults.
The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.
The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.
“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.
“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”
“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
Need for aggressive CVD risk reduction
The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.
“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”
However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.
“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.
“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.
Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
ADA report already recommends testing these biomarkers for HF
However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.
“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.
The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.
“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.
All study participants had recorded measures of hs-cTnT and NT-proBNP.
The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.
The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.
“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
Diabetes linked with a doubled prevalence of elevated hs-cTnT
After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.
“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”
In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.
Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.
However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.
The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.
The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.
A version of this article first appeared on Medscape.com.
– based on data from a representative sample of more than 10,000 U.S. adults.
The finding suggests hs-cTnT maybe a useful marker for adults with diabetes who could benefit from more aggressive CVD risk reduction despite having no clinical indications of CVD.
The results “highlight the substantial burden of subclinical CVD in persons with diabetes and emphasize the importance of early detection and treatment of CVD for this high-risk population,” say the authors of the research, published in the Journal of the American Heart Association.
“This is the first study to examine subclinical CVD, defined by elevated cardiac biomarkers, in a nationally representative population of adults with or without diabetes. It provides novel information on the high burden of subclinical CVD [in American adults with diabetes] and the potential utility of hs-cTnT for monitoring this risk in people with diabetes,” said Elizabeth Selvin, PhD, senior author and a professor of epidemiology at Johns Hopkins University, Baltimore.
“What we are seeing is that many people with type 2 diabetes who have not had a heart attack or a history of cardiovascular disease are at high risk for cardiovascular complications,” added Dr. Selvin in an AHA press release. “When we look at the whole population of people diagnosed with type 2 diabetes, about 27 million adults in the U.S., according to the [Centers for Disease Control and Prevention], some are at low risk and some are at high risk for cardiovascular disease, so the open question is: ‘Who is most at risk?’ These cardiac biomarkers give us a window into cardiovascular risk in people who otherwise might not be recognized as highest risk.”
“Our results provide evidence to support use of cardiac biomarkers for routine risk monitoring in high-risk populations such as people with diabetes,” Dr. Selvin noted in an interview.
Need for aggressive CVD risk reduction
The findings also indicate that people with diabetes and an elevated hs-cTnT “should be targeted for aggressive cardiovascular risk reduction, including lifestyle interventions, weight loss, and treatment with statins, blood pressure medications, and cardioprotective therapies such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists,” Dr. Selvin added.
“Cholesterol is often the factor that we target to reduce the risk of cardiovascular disease in people with type 2 diabetes,” she observed. “However, type 2 diabetes may have a direct effect on the heart not related to cholesterol levels. If type 2 diabetes is directly causing damage to the small vessels in the heart unrelated to cholesterol plaque buildup, then cholesterol-lowering medications are not going to prevent cardiac damage,” Dr. Selvin explained. “Our research suggests that additional non–statin-related therapies are needed to lower the cardiovascular disease risk in people with type 2 diabetes.”
However, she noted that a necessary step prior to formally recommending such a strategy is to run clinical trials to assess the efficacy of specific treatments, such as SGLT-2 inhibitors and GLP-1 agonists, in people with diabetes and elevated hs-cTnT.
“Randomized controlled trials would be best to test the relevance of measuring these biomarkers to assess risk in asymptomatic people with diabetes,” as well as prospective study of the value of hs-cTnT to guide treatment, commented Robert H. Eckel, MD, an endocrinologist affiliated with the University of Colorado at Denver, Aurora.
“I doubt measurements [of hs-cTnT] would be reimbursed [by third-party payers] if carried out without such outcome data,” he added.
Dr. Eckel also highlights the need to further validate in additional cohorts the link between elevations in hs-cTnT and CVD events in adults with diabetes, and to confirm that elevated levels of another cardiac biomarker – N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) – do not work as well as troponin as a risk marker for people with diabetes, another finding of the study.
ADA report already recommends testing these biomarkers for HF
However, a consensus report published in 2022 by the American Diabetes Association laid out the case for routinely and regularly measuring levels of both high sensitivity cardiac troponin and natriuretic peptides in people with diabetes for early identification of incident heart failure.
“Among individuals with diabetes, measurement of a natriuretic peptide or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest heart failure stages and implement strategies to prevent transition to symptomatic heart failure,” noted the ADA consensus report on heart failure.
The new study run by Dr. Selvin and coauthors used data collected by the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 from U.S. adults who were at least 20 years old and had no history of CVD: myocardial infarction, stroke, coronary heart disease, or heart failure. This included 9,273 people without diabetes and 1,031 with diabetes, defined as a prior diagnosis or hemoglobin A1c of at least 6.5%.
“Cardiovascular risk varies substantially in adults with type 2 diabetes, highlighting the need for accurate risk stratification,” the authors observed.
All study participants had recorded measures of hs-cTnT and NT-proBNP.
The researchers considered an hs-cTnT level of greater than 14 ng/L and an NT-proBNP level of greater than 125 pg/mL as indicators of subclinical CVD.
The crude prevalence of elevated NT-proBNP was 33.4% among those with diabetes and 16.1% in those without diabetes. Elevated hs-cTnT occurred in 19% of those with diabetes and in 5% of those without diabetes. Elevated levels of both markers existed in 9% of those with diabetes and in 3% of those without diabetes.
“Approximately one in three adults with diabetes had subclinical CVD, with 19% having elevated levels of hs-cTnT, 23% having elevated NT-proBNP, and 9% having elevations in both cardiac biomarkers,” the researchers noted.
Diabetes linked with a doubled prevalence of elevated hs-cTnT
After adjustment for several demographic variables as well as traditional CVD risk factors, people with diabetes had a significant 98% higher rate of elevated hs-cTnT, compared with those without diabetes. But after similar adjustments, the rate of elevated NT-proBNP was significantly lower among people with diabetes, compared with controls, by a relative reduction of 24%.
“Our findings suggest that, in people with diabetes, hs-cTnT may be more useful [than NT-proBNP] for general risk monitoring, as its interpretation is less complicated,” said Dr. Selvin, who explained that “NT-proBNP is affected by overweight and obesity.”
In people with diabetes, the age-adjusted prevalence of elevated hs-cTnT ran higher in those with longer duration diabetes, and in those with less well-controlled diabetes based on a higher level of A1c. Neither of these factors showed any significant relationship with measured levels of NT-proBNP.
Further analysis linked the NHANES findings during 1999-2004 with U.S. national death records through the end of 2019. This showed that elevated levels of both hs-cTnT and NT-proBNP significantly linked with subsequently higher rates of all-cause mortality among people with diabetes. Elevated hs-cTnT linked with a 77% increased mortality and NT-proBNP linked with a 78% increased rate, compared with people with diabetes and no elevations in these markers, after adjustment for demographic variables and CVD risk factors.
However, for the outcome of cardiovascular death, elevated hs-cTnT linked with a nonsignificant 54% relative increase, while elevated NT-proBNP linked with a significant 2.46-fold relative increase.
The study “adds new data on biomarkers that are not routinely measured in asymptomatic people with or without diabetes” and the relationships of these markers to CVD mortality and all-cause mortality, Dr. Eckel concluded.
The study received no commercial funding, but used reagents donated by Abbott Laboratories, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. Dr. Selvin and Dr. Eckel had no disclosures.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Overweight in heterozygous FH tied to even higher CAD risk
MANNHEIM, GERMANY – – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.
Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.
Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.
Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.
She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”
The research was presented at the annual meeting of the European Atherosclerosis Society.
Tended to be thin
Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.
However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.
In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.
As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”
Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).
Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”
In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”
Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”
Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”
The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.
Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.
Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”
Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
More with than without
Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”
Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.
Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.
They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.
Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.
For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.
Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.
Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.
In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.
Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.
Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.
Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).
Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.
Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).
The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.
No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY – – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.
Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.
Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.
Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.
She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”
The research was presented at the annual meeting of the European Atherosclerosis Society.
Tended to be thin
Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.
However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.
In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.
As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”
Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).
Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”
In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”
Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”
Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”
The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.
Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.
Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”
Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
More with than without
Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”
Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.
Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.
They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.
Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.
For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.
Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.
Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.
In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.
Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.
Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.
Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).
Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.
Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).
The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.
No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.
A version of this article first appeared on Medscape.com.
MANNHEIM, GERMANY – – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.
Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.
Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.
Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.
She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”
The research was presented at the annual meeting of the European Atherosclerosis Society.
Tended to be thin
Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.
However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.
In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.
As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”
Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).
Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”
In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”
Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”
Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”
The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.
Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.
Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”
Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
More with than without
Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”
Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.
Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.
They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.
Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.
For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.
Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.
Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.
In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.
Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.
Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.
Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).
Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.
Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).
The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.
No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.
A version of this article first appeared on Medscape.com.
AT EAS 2023
PTSD, anxiety linked to out-of-hospital cardiac arrest
Investigators compared more than 35,000 OHCA case patients with a similar number of matched control persons and found an almost 1.5 times higher hazard of long-term stress conditions among OHCA case patients, compared with control persons, with a similar hazard for anxiety. Posttraumatic stress disorder was associated with an almost twofold higher risk of OHCA.
The findings applied equally to men and women and were independent of the presence of cardiovascular disease (CVD).
“This study raises awareness of the higher risks of OHCA and early risk monitoring to prevent OHCA in patients with stress-related disorders and anxiety,” write Talip Eroglu, of the department of cardiology, Copenhagen University Hospital, and colleagues.
The study was published online in BMJ Open Heart.
Stress disorders and anxiety overrepresented
OHCA “predominantly arises from lethal cardiac arrhythmias ... that occur most frequently in the setting of coronary heart disease,” the authors write. However, increasing evidence suggests that rates of OHCA may also be increased in association with noncardiac diseases.
Individuals with stress-related disorders and anxiety are “overrepresented” among victims of cardiac arrest as well as those with multiple CVDs. But previous studies of OHCA have been limited by small numbers of cardiac arrests. In addition, those studies involved only data from selected populations or used in-hospital diagnosis to identify cardiac arrest, thereby potentially omitting OHCA patients who died prior to hospital admission.
The researchers therefore turned to data from Danish health registries that include a large, unselected cohort of patients with OHCA to investigate whether long-term stress conditions (that is, PTSD and adjustment disorder) or anxiety disorder were associated with OHCA.
They stratified the cohort according to sex, age, and CVD to identify which risk factor confers the highest risk of OHCA in patients with long-term stress conditions or anxiety, and they conducted sensitivity analyses of potential confounders, such as depression.
The design was a nested-case control model in which records at an individual patient level across registries were cross-linked to data from other national registries and were compared to matched control persons from the general population (35,195 OHCAs and 351,950 matched control persons; median IQR age, 72 [62-81] years; 66.82% men).
The prevalence of comorbidities and use of cardiovascular drugs were higher among OHCA case patients than among non-OHCA control persons.
Keep aware of stress and anxiety as risk factors
Among OHCA and non-OHCA participants, long-term stress conditions were diagnosed in 0.92% and 0.45%, respectively. Anxiety was diagnosed in 0.85% of OHCA case patients and in 0.37% of non-OHCA control persons.
These conditions were associated with a higher rate of OHCA after adjustment for common OHCA risk factors.
There were no significant differences in results when the researchers adjusted for the use of anxiolytics and antidepressants.
When they examined the prevalence of concomitant medication use or comorbidities, they found that depression was more frequent among patients with long-term stress and anxiety, compared with individuals with neither of those diagnoses. Additionally, patients with long-term stress and anxiety more often used anxiolytics, antidepressants, and QT-prolonging drugs.
Stratification of the analyses according to sex revealed that the OHCA rate was increased in both women and men with long-term stress and anxiety. There were no significant differences between the sexes. There were also no significant differences between the association among different age groups, nor between patients with and those without CVD, ischemic heart disease, or heart failure.
Previous research has shown associations of stress-related disorders or anxiety with cardiovascular outcomes, including myocardial infarction, heart failure, and cerebrovascular disease. These disorders might be “biological mediators in the causal pathway of OHCA” and contribute to the increased OHCA rate associated with stress-related disorders and anxiety, the authors suggest.
Nevertheless, they note, stress-related disorders and anxiety remained significantly associated with OHCA after controlling for these variables, “suggesting that it is unlikely that traditional risk factors of OHCA alone explain this relationship.”
They suggest several potential mechanisms. One is that the relationship is likely mediated by the activity of the sympathetic autonomic nervous system, which “leads to an increase in heart rate, release of neurotransmitters into the circulation, and local release of neurotransmitters in the heart.”
Each of these factors “may potentially influence cardiac electrophysiology and facilitate ventricular arrhythmias and OHCA.”
In addition to a biological mechanism, behavioral and psychosocial factors may also contribute to OHCA risk, since stress-related disorders and anxiety “often lead to unhealthy lifestyle, such as smoking and lower physical activity, which in turn may increase the risk of OHCA.” Given the absence of data on these features in the registries the investigators used, they were unable to account for them.
However, “it is unlikely that knowledge of these factors would have altered our conclusions considering that we have adjusted for all the relevant cardiovascular comorbidities.”
Similarly, other psychiatric disorders, such as depression, can contribute to OHCA risk, but they adjusted for depression in their multivariable analyses.
“Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients,” they conclude.
Detrimental to the heart, not just the psyche
Glenn Levine, MD, master clinician and professor of medicine, Baylor College of Medicine, Houston, called it an “important study in that it is a large, nationwide cohort study and thus provides important information to complement much smaller, focused studies.”
Like those other studies, “it finds that negative psychological health, specifically, long-term stress (as well as anxiety), is associated with a significantly increased risk of out-of-hospital cardiac arrest,” continued Dr. Levine, who is the chief of the cardiology section at Michael E. DeBakey VA Medical Center, Houston, and was not involved with the study.
Dr. Levine thinks the study “does a good job, as best one can for such a study, in trying to control for other factors, and zeroing in specifically on stress (and anxiety), trying to assess their independent contributions to the risk of developing cardiac arrest.”
The take-home message for clinicians and patients “is that negative psychological stress factors, such as stress and anxiety, are not only detrimental to one’s psychological health but likely increase one’s risk for adverse cardiac events, such as cardiac arrest,” he stated.
No specific funding for the study was disclosed. Mr. Eroglu has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Levine reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators compared more than 35,000 OHCA case patients with a similar number of matched control persons and found an almost 1.5 times higher hazard of long-term stress conditions among OHCA case patients, compared with control persons, with a similar hazard for anxiety. Posttraumatic stress disorder was associated with an almost twofold higher risk of OHCA.
The findings applied equally to men and women and were independent of the presence of cardiovascular disease (CVD).
“This study raises awareness of the higher risks of OHCA and early risk monitoring to prevent OHCA in patients with stress-related disorders and anxiety,” write Talip Eroglu, of the department of cardiology, Copenhagen University Hospital, and colleagues.
The study was published online in BMJ Open Heart.
Stress disorders and anxiety overrepresented
OHCA “predominantly arises from lethal cardiac arrhythmias ... that occur most frequently in the setting of coronary heart disease,” the authors write. However, increasing evidence suggests that rates of OHCA may also be increased in association with noncardiac diseases.
Individuals with stress-related disorders and anxiety are “overrepresented” among victims of cardiac arrest as well as those with multiple CVDs. But previous studies of OHCA have been limited by small numbers of cardiac arrests. In addition, those studies involved only data from selected populations or used in-hospital diagnosis to identify cardiac arrest, thereby potentially omitting OHCA patients who died prior to hospital admission.
The researchers therefore turned to data from Danish health registries that include a large, unselected cohort of patients with OHCA to investigate whether long-term stress conditions (that is, PTSD and adjustment disorder) or anxiety disorder were associated with OHCA.
They stratified the cohort according to sex, age, and CVD to identify which risk factor confers the highest risk of OHCA in patients with long-term stress conditions or anxiety, and they conducted sensitivity analyses of potential confounders, such as depression.
The design was a nested-case control model in which records at an individual patient level across registries were cross-linked to data from other national registries and were compared to matched control persons from the general population (35,195 OHCAs and 351,950 matched control persons; median IQR age, 72 [62-81] years; 66.82% men).
The prevalence of comorbidities and use of cardiovascular drugs were higher among OHCA case patients than among non-OHCA control persons.
Keep aware of stress and anxiety as risk factors
Among OHCA and non-OHCA participants, long-term stress conditions were diagnosed in 0.92% and 0.45%, respectively. Anxiety was diagnosed in 0.85% of OHCA case patients and in 0.37% of non-OHCA control persons.
These conditions were associated with a higher rate of OHCA after adjustment for common OHCA risk factors.
There were no significant differences in results when the researchers adjusted for the use of anxiolytics and antidepressants.
When they examined the prevalence of concomitant medication use or comorbidities, they found that depression was more frequent among patients with long-term stress and anxiety, compared with individuals with neither of those diagnoses. Additionally, patients with long-term stress and anxiety more often used anxiolytics, antidepressants, and QT-prolonging drugs.
Stratification of the analyses according to sex revealed that the OHCA rate was increased in both women and men with long-term stress and anxiety. There were no significant differences between the sexes. There were also no significant differences between the association among different age groups, nor between patients with and those without CVD, ischemic heart disease, or heart failure.
Previous research has shown associations of stress-related disorders or anxiety with cardiovascular outcomes, including myocardial infarction, heart failure, and cerebrovascular disease. These disorders might be “biological mediators in the causal pathway of OHCA” and contribute to the increased OHCA rate associated with stress-related disorders and anxiety, the authors suggest.
Nevertheless, they note, stress-related disorders and anxiety remained significantly associated with OHCA after controlling for these variables, “suggesting that it is unlikely that traditional risk factors of OHCA alone explain this relationship.”
They suggest several potential mechanisms. One is that the relationship is likely mediated by the activity of the sympathetic autonomic nervous system, which “leads to an increase in heart rate, release of neurotransmitters into the circulation, and local release of neurotransmitters in the heart.”
Each of these factors “may potentially influence cardiac electrophysiology and facilitate ventricular arrhythmias and OHCA.”
In addition to a biological mechanism, behavioral and psychosocial factors may also contribute to OHCA risk, since stress-related disorders and anxiety “often lead to unhealthy lifestyle, such as smoking and lower physical activity, which in turn may increase the risk of OHCA.” Given the absence of data on these features in the registries the investigators used, they were unable to account for them.
However, “it is unlikely that knowledge of these factors would have altered our conclusions considering that we have adjusted for all the relevant cardiovascular comorbidities.”
Similarly, other psychiatric disorders, such as depression, can contribute to OHCA risk, but they adjusted for depression in their multivariable analyses.
“Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients,” they conclude.
Detrimental to the heart, not just the psyche
Glenn Levine, MD, master clinician and professor of medicine, Baylor College of Medicine, Houston, called it an “important study in that it is a large, nationwide cohort study and thus provides important information to complement much smaller, focused studies.”
Like those other studies, “it finds that negative psychological health, specifically, long-term stress (as well as anxiety), is associated with a significantly increased risk of out-of-hospital cardiac arrest,” continued Dr. Levine, who is the chief of the cardiology section at Michael E. DeBakey VA Medical Center, Houston, and was not involved with the study.
Dr. Levine thinks the study “does a good job, as best one can for such a study, in trying to control for other factors, and zeroing in specifically on stress (and anxiety), trying to assess their independent contributions to the risk of developing cardiac arrest.”
The take-home message for clinicians and patients “is that negative psychological stress factors, such as stress and anxiety, are not only detrimental to one’s psychological health but likely increase one’s risk for adverse cardiac events, such as cardiac arrest,” he stated.
No specific funding for the study was disclosed. Mr. Eroglu has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Levine reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Investigators compared more than 35,000 OHCA case patients with a similar number of matched control persons and found an almost 1.5 times higher hazard of long-term stress conditions among OHCA case patients, compared with control persons, with a similar hazard for anxiety. Posttraumatic stress disorder was associated with an almost twofold higher risk of OHCA.
The findings applied equally to men and women and were independent of the presence of cardiovascular disease (CVD).
“This study raises awareness of the higher risks of OHCA and early risk monitoring to prevent OHCA in patients with stress-related disorders and anxiety,” write Talip Eroglu, of the department of cardiology, Copenhagen University Hospital, and colleagues.
The study was published online in BMJ Open Heart.
Stress disorders and anxiety overrepresented
OHCA “predominantly arises from lethal cardiac arrhythmias ... that occur most frequently in the setting of coronary heart disease,” the authors write. However, increasing evidence suggests that rates of OHCA may also be increased in association with noncardiac diseases.
Individuals with stress-related disorders and anxiety are “overrepresented” among victims of cardiac arrest as well as those with multiple CVDs. But previous studies of OHCA have been limited by small numbers of cardiac arrests. In addition, those studies involved only data from selected populations or used in-hospital diagnosis to identify cardiac arrest, thereby potentially omitting OHCA patients who died prior to hospital admission.
The researchers therefore turned to data from Danish health registries that include a large, unselected cohort of patients with OHCA to investigate whether long-term stress conditions (that is, PTSD and adjustment disorder) or anxiety disorder were associated with OHCA.
They stratified the cohort according to sex, age, and CVD to identify which risk factor confers the highest risk of OHCA in patients with long-term stress conditions or anxiety, and they conducted sensitivity analyses of potential confounders, such as depression.
The design was a nested-case control model in which records at an individual patient level across registries were cross-linked to data from other national registries and were compared to matched control persons from the general population (35,195 OHCAs and 351,950 matched control persons; median IQR age, 72 [62-81] years; 66.82% men).
The prevalence of comorbidities and use of cardiovascular drugs were higher among OHCA case patients than among non-OHCA control persons.
Keep aware of stress and anxiety as risk factors
Among OHCA and non-OHCA participants, long-term stress conditions were diagnosed in 0.92% and 0.45%, respectively. Anxiety was diagnosed in 0.85% of OHCA case patients and in 0.37% of non-OHCA control persons.
These conditions were associated with a higher rate of OHCA after adjustment for common OHCA risk factors.
There were no significant differences in results when the researchers adjusted for the use of anxiolytics and antidepressants.
When they examined the prevalence of concomitant medication use or comorbidities, they found that depression was more frequent among patients with long-term stress and anxiety, compared with individuals with neither of those diagnoses. Additionally, patients with long-term stress and anxiety more often used anxiolytics, antidepressants, and QT-prolonging drugs.
Stratification of the analyses according to sex revealed that the OHCA rate was increased in both women and men with long-term stress and anxiety. There were no significant differences between the sexes. There were also no significant differences between the association among different age groups, nor between patients with and those without CVD, ischemic heart disease, or heart failure.
Previous research has shown associations of stress-related disorders or anxiety with cardiovascular outcomes, including myocardial infarction, heart failure, and cerebrovascular disease. These disorders might be “biological mediators in the causal pathway of OHCA” and contribute to the increased OHCA rate associated with stress-related disorders and anxiety, the authors suggest.
Nevertheless, they note, stress-related disorders and anxiety remained significantly associated with OHCA after controlling for these variables, “suggesting that it is unlikely that traditional risk factors of OHCA alone explain this relationship.”
They suggest several potential mechanisms. One is that the relationship is likely mediated by the activity of the sympathetic autonomic nervous system, which “leads to an increase in heart rate, release of neurotransmitters into the circulation, and local release of neurotransmitters in the heart.”
Each of these factors “may potentially influence cardiac electrophysiology and facilitate ventricular arrhythmias and OHCA.”
In addition to a biological mechanism, behavioral and psychosocial factors may also contribute to OHCA risk, since stress-related disorders and anxiety “often lead to unhealthy lifestyle, such as smoking and lower physical activity, which in turn may increase the risk of OHCA.” Given the absence of data on these features in the registries the investigators used, they were unable to account for them.
However, “it is unlikely that knowledge of these factors would have altered our conclusions considering that we have adjusted for all the relevant cardiovascular comorbidities.”
Similarly, other psychiatric disorders, such as depression, can contribute to OHCA risk, but they adjusted for depression in their multivariable analyses.
“Awareness of the higher risks of OHCA in patients with stress-related disorders and anxiety is important when treating these patients,” they conclude.
Detrimental to the heart, not just the psyche
Glenn Levine, MD, master clinician and professor of medicine, Baylor College of Medicine, Houston, called it an “important study in that it is a large, nationwide cohort study and thus provides important information to complement much smaller, focused studies.”
Like those other studies, “it finds that negative psychological health, specifically, long-term stress (as well as anxiety), is associated with a significantly increased risk of out-of-hospital cardiac arrest,” continued Dr. Levine, who is the chief of the cardiology section at Michael E. DeBakey VA Medical Center, Houston, and was not involved with the study.
Dr. Levine thinks the study “does a good job, as best one can for such a study, in trying to control for other factors, and zeroing in specifically on stress (and anxiety), trying to assess their independent contributions to the risk of developing cardiac arrest.”
The take-home message for clinicians and patients “is that negative psychological stress factors, such as stress and anxiety, are not only detrimental to one’s psychological health but likely increase one’s risk for adverse cardiac events, such as cardiac arrest,” he stated.
No specific funding for the study was disclosed. Mr. Eroglu has disclosed no relevant financial relationships. The other authors’ disclosures are listed in the original article. Dr. Levine reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ OPEN HEART
Plant-based diet tied to healthier blood lipid levels
, in a new meta-analysis of 30 trials.
The findings suggest that “plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease,” write Caroline Amelie Koch, a medical student at the University of Copenhagen, and colleagues. Their findings were published online in the European Heart Journal (2023 May 24. doi: 10.1093/eurheartj/ehad211).
“Vegetarian and vegan diets were associated with a 14% reduction in all artery-clogging lipoproteins as indicated by apoB,” senior author Ruth Frikke-Schmidt, DMSc, PhD, Rigshospitalet, Copenhagen, and professor, University of Copenhagen, said in a press release from her university.
“This corresponds to a third of the effect of taking cholesterol-lowering medications such as statins,” she added, “and would result in a 7% reduction in the risk of cardiovascular disease in someone who maintained a plant-based diet for 5 years.”
“Importantly, we found similar results, across continents, ages, different ranges of body mass index, and among people in different states of health,” Dr. Frikke-Schmidt stressed.
And combining statins with plant-based diets would likely produce a synergistic effect, she speculated.
“If people start eating vegetarian or vegan diets from an early age,” she said, “the potential for reducing the risk of cardiovascular disease caused by blocked arteries is substantial.”
In addition, the researchers conclude: “Shifting to plant-based diets at a populational level will reduce emissions of greenhouse gases considerably – together making these diets efficient means [moving] towards a more sustainable development, while at the same time reducing the growing burden of atherosclerotic cardiovascular disease.”
More support for vegan, vegetarian diets
These new findings “add to the body of evidence supporting favorable effects of healthy vegan and vegetarian dietary patterns on circulating levels of LDL-C and atherogenic lipoproteins, which would be expected to reduce ASCVD risk,” Kevin C. Maki, PhD, and Carol Kirkpatrick, PhD, MPH, write in an accompanying editorial.
“While it is not necessary to entirely omit foods such as meat, poultry, and fish/seafood to follow a recommended dietary pattern, reducing consumption of such foods is a reasonable option for those who prefer to do so,” note Dr. Maki, of Indiana University School of Public Health, Bloomington, and Kirkpatrick, of Idaho State University, Pocatello.
Plant-based diet needs to be ‘well-planned’
Several experts who were not involved in this meta-analysis shed light on the study and its implications in comments to the U.K. Science Media Center.
“Although a vegetarian and vegan diet can be very healthy and beneficial with respect to cardiovascular risk, it is important that it is well planned so that nutrients it can be low in are included, including iron, iodine, vitamin B12, and vitamin D,” said Duane Mellor, PhD, a registered dietitian and senior lecturer, Aston Medical School, Aston University, Birmingham, England.
Some people “may find it easier to follow a Mediterranean-style diet that features plenty of fruit, vegetables, pulses, wholegrains, fish, eggs and low-fat dairy, with only small amounts of meat,” Tracy Parker, senior dietitian at the British Heart Foundation, London, suggested.
“There is considerable evidence that this type of diet can help lower your risk of developing heart and circulatory diseases by improving cholesterol and blood pressure levels, reducing inflammation, and controlling blood glucose levels,” she added.
And Aedin Cassidy, PhD, chair in nutrition & preventative medicine, Queen’s University Belfast (Ireland), noted that “not all plant-based diets are equal. Healthy plant-based diets, characterized by fruits, vegetables, and whole grains improve health, but other plant diets (for example, those including refined carbohydrates, processed foods high in fat/salt, etc.) do not.”
This new study shows that plant-based diets have the potential to improve health by improving blood lipids, “but this is one of many potential mechanisms, including impact on blood pressure, weight maintenance, and blood sugars,” she added.
“This work represents a well-conducted analysis of 30 clinical trials involving over two thousand participants and highlights the value of a vegetarian diet in reducing the risk of heart attack or stroke through reduction in blood cholesterol levels,” said Robert Storey, BM, DM, professor of cardiology, University of Sheffield, U.K.
However, it also demonstrates that the impact of diet on an individual’s cholesterol level is relatively limited, he added.
“This is because people inherit the tendency for their livers to produce too much cholesterol, meaning that high cholesterol is more strongly influenced by our genes than by our diet,” he explained.
This is “why statins are needed to block cholesterol production in people who are at higher risk of or have already suffered from a heart attack, stroke, or other illness related to cholesterol build-up in blood vessels.”
Beneficial effect on ApoB, LDL-C, and total cholesterol
ApoB is the main apolipoprotein in LDL-C (“bad” cholesterol), the researchers note. Previous studies have shown that LDL-C and apoB-containing particles are associated with increased risk of ASCVD.
They aimed to estimate the effect of vegetarian or vegan diets on blood levels of total cholesterol, LDL-C, triglycerides, and apoB in people randomized to a vegetarian or vegan diet versus an omnivorous diet (that is, including meat and dairy).
They identified 30 studies published between 1982 and 2022 and conducted in the United States (18 studies), Sweden (2), Finland (2), South Korea (2), Australia (1), Brazil (1), Czech Republic (1), Italy (1), Iran (1), and New Zealand (1).
The diet interventions lasted from 10 days to 5 years with a mean of 29 weeks (15 studies ≤ 3 months; 12 studies 3-12 months; and three studies > 1 year). Nine studies used a crossover design, and the rest used a parallel design whereby participants followed only one diet.
The studies had 11 to 291 participants (mean, 79 participants) with a mean BMI of 21.5-35.1 kg/m2 and a mean age of 20-67 years. Thirteen studies included participants treated with lipid-lowering therapy at baseline.
The dietary intervention was vegetarian in 15 trials (three lacto-vegetarian and 12 lacto-ovo-vegetarian) and vegan in the other 15 trials.
On average, compared with people eating an omnivore diet, people eating a plant-based diet had a 7% reduction in total cholesterol from baseline (–0.34 mmol/L), a 10% reduction in LDL-C from baseline (–0.30 mmol/L), and a 14% reduction in apoB from baseline (–12.9 mg/dL) (all P < .01).
The effects were similar across age, continent, study duration, health status, intervention diet, intervention program, and study design subgroups.
There was no significant difference in triglyceride levels in patients in the omnivore versus plant-based diet groups.
Such diets could considerably reduce greenhouse gases
Senior author Dr. Frikke-Schmidt noted: “Recent systematic reviews have shown that if the populations of high-income countries shift to plant-based diets, this can reduce net emissions of greenhouse gases by between 35% to 49%.”
“Plant-based diets are key instruments for changing food production to more environmentally sustainable forms, while at the same time reducing the burden of cardiovascular disease” in an aging population, she said.
“We should be eating a varied, plant-rich diet, not too much, and quenching our thirst with water,” she concluded.
The study was funded by the Lundbeck Foundation, the Danish Heart Foundation, and the Leducq Foundation. The authors, editorialists, Ms. Parker, Dr. Cassidy, and Dr. Storey have reported no relevant financial relationships. Dr. Mellor has disclosed that he is a vegetarian.
A version of this article first appeared on Medscape.com.
, in a new meta-analysis of 30 trials.
The findings suggest that “plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease,” write Caroline Amelie Koch, a medical student at the University of Copenhagen, and colleagues. Their findings were published online in the European Heart Journal (2023 May 24. doi: 10.1093/eurheartj/ehad211).
“Vegetarian and vegan diets were associated with a 14% reduction in all artery-clogging lipoproteins as indicated by apoB,” senior author Ruth Frikke-Schmidt, DMSc, PhD, Rigshospitalet, Copenhagen, and professor, University of Copenhagen, said in a press release from her university.
“This corresponds to a third of the effect of taking cholesterol-lowering medications such as statins,” she added, “and would result in a 7% reduction in the risk of cardiovascular disease in someone who maintained a plant-based diet for 5 years.”
“Importantly, we found similar results, across continents, ages, different ranges of body mass index, and among people in different states of health,” Dr. Frikke-Schmidt stressed.
And combining statins with plant-based diets would likely produce a synergistic effect, she speculated.
“If people start eating vegetarian or vegan diets from an early age,” she said, “the potential for reducing the risk of cardiovascular disease caused by blocked arteries is substantial.”
In addition, the researchers conclude: “Shifting to plant-based diets at a populational level will reduce emissions of greenhouse gases considerably – together making these diets efficient means [moving] towards a more sustainable development, while at the same time reducing the growing burden of atherosclerotic cardiovascular disease.”
More support for vegan, vegetarian diets
These new findings “add to the body of evidence supporting favorable effects of healthy vegan and vegetarian dietary patterns on circulating levels of LDL-C and atherogenic lipoproteins, which would be expected to reduce ASCVD risk,” Kevin C. Maki, PhD, and Carol Kirkpatrick, PhD, MPH, write in an accompanying editorial.
“While it is not necessary to entirely omit foods such as meat, poultry, and fish/seafood to follow a recommended dietary pattern, reducing consumption of such foods is a reasonable option for those who prefer to do so,” note Dr. Maki, of Indiana University School of Public Health, Bloomington, and Kirkpatrick, of Idaho State University, Pocatello.
Plant-based diet needs to be ‘well-planned’
Several experts who were not involved in this meta-analysis shed light on the study and its implications in comments to the U.K. Science Media Center.
“Although a vegetarian and vegan diet can be very healthy and beneficial with respect to cardiovascular risk, it is important that it is well planned so that nutrients it can be low in are included, including iron, iodine, vitamin B12, and vitamin D,” said Duane Mellor, PhD, a registered dietitian and senior lecturer, Aston Medical School, Aston University, Birmingham, England.
Some people “may find it easier to follow a Mediterranean-style diet that features plenty of fruit, vegetables, pulses, wholegrains, fish, eggs and low-fat dairy, with only small amounts of meat,” Tracy Parker, senior dietitian at the British Heart Foundation, London, suggested.
“There is considerable evidence that this type of diet can help lower your risk of developing heart and circulatory diseases by improving cholesterol and blood pressure levels, reducing inflammation, and controlling blood glucose levels,” she added.
And Aedin Cassidy, PhD, chair in nutrition & preventative medicine, Queen’s University Belfast (Ireland), noted that “not all plant-based diets are equal. Healthy plant-based diets, characterized by fruits, vegetables, and whole grains improve health, but other plant diets (for example, those including refined carbohydrates, processed foods high in fat/salt, etc.) do not.”
This new study shows that plant-based diets have the potential to improve health by improving blood lipids, “but this is one of many potential mechanisms, including impact on blood pressure, weight maintenance, and blood sugars,” she added.
“This work represents a well-conducted analysis of 30 clinical trials involving over two thousand participants and highlights the value of a vegetarian diet in reducing the risk of heart attack or stroke through reduction in blood cholesterol levels,” said Robert Storey, BM, DM, professor of cardiology, University of Sheffield, U.K.
However, it also demonstrates that the impact of diet on an individual’s cholesterol level is relatively limited, he added.
“This is because people inherit the tendency for their livers to produce too much cholesterol, meaning that high cholesterol is more strongly influenced by our genes than by our diet,” he explained.
This is “why statins are needed to block cholesterol production in people who are at higher risk of or have already suffered from a heart attack, stroke, or other illness related to cholesterol build-up in blood vessels.”
Beneficial effect on ApoB, LDL-C, and total cholesterol
ApoB is the main apolipoprotein in LDL-C (“bad” cholesterol), the researchers note. Previous studies have shown that LDL-C and apoB-containing particles are associated with increased risk of ASCVD.
They aimed to estimate the effect of vegetarian or vegan diets on blood levels of total cholesterol, LDL-C, triglycerides, and apoB in people randomized to a vegetarian or vegan diet versus an omnivorous diet (that is, including meat and dairy).
They identified 30 studies published between 1982 and 2022 and conducted in the United States (18 studies), Sweden (2), Finland (2), South Korea (2), Australia (1), Brazil (1), Czech Republic (1), Italy (1), Iran (1), and New Zealand (1).
The diet interventions lasted from 10 days to 5 years with a mean of 29 weeks (15 studies ≤ 3 months; 12 studies 3-12 months; and three studies > 1 year). Nine studies used a crossover design, and the rest used a parallel design whereby participants followed only one diet.
The studies had 11 to 291 participants (mean, 79 participants) with a mean BMI of 21.5-35.1 kg/m2 and a mean age of 20-67 years. Thirteen studies included participants treated with lipid-lowering therapy at baseline.
The dietary intervention was vegetarian in 15 trials (three lacto-vegetarian and 12 lacto-ovo-vegetarian) and vegan in the other 15 trials.
On average, compared with people eating an omnivore diet, people eating a plant-based diet had a 7% reduction in total cholesterol from baseline (–0.34 mmol/L), a 10% reduction in LDL-C from baseline (–0.30 mmol/L), and a 14% reduction in apoB from baseline (–12.9 mg/dL) (all P < .01).
The effects were similar across age, continent, study duration, health status, intervention diet, intervention program, and study design subgroups.
There was no significant difference in triglyceride levels in patients in the omnivore versus plant-based diet groups.
Such diets could considerably reduce greenhouse gases
Senior author Dr. Frikke-Schmidt noted: “Recent systematic reviews have shown that if the populations of high-income countries shift to plant-based diets, this can reduce net emissions of greenhouse gases by between 35% to 49%.”
“Plant-based diets are key instruments for changing food production to more environmentally sustainable forms, while at the same time reducing the burden of cardiovascular disease” in an aging population, she said.
“We should be eating a varied, plant-rich diet, not too much, and quenching our thirst with water,” she concluded.
The study was funded by the Lundbeck Foundation, the Danish Heart Foundation, and the Leducq Foundation. The authors, editorialists, Ms. Parker, Dr. Cassidy, and Dr. Storey have reported no relevant financial relationships. Dr. Mellor has disclosed that he is a vegetarian.
A version of this article first appeared on Medscape.com.
, in a new meta-analysis of 30 trials.
The findings suggest that “plant-based diets have the potential to lessen the atherosclerotic burden from atherogenic lipoproteins and thereby reduce the risk of cardiovascular disease,” write Caroline Amelie Koch, a medical student at the University of Copenhagen, and colleagues. Their findings were published online in the European Heart Journal (2023 May 24. doi: 10.1093/eurheartj/ehad211).
“Vegetarian and vegan diets were associated with a 14% reduction in all artery-clogging lipoproteins as indicated by apoB,” senior author Ruth Frikke-Schmidt, DMSc, PhD, Rigshospitalet, Copenhagen, and professor, University of Copenhagen, said in a press release from her university.
“This corresponds to a third of the effect of taking cholesterol-lowering medications such as statins,” she added, “and would result in a 7% reduction in the risk of cardiovascular disease in someone who maintained a plant-based diet for 5 years.”
“Importantly, we found similar results, across continents, ages, different ranges of body mass index, and among people in different states of health,” Dr. Frikke-Schmidt stressed.
And combining statins with plant-based diets would likely produce a synergistic effect, she speculated.
“If people start eating vegetarian or vegan diets from an early age,” she said, “the potential for reducing the risk of cardiovascular disease caused by blocked arteries is substantial.”
In addition, the researchers conclude: “Shifting to plant-based diets at a populational level will reduce emissions of greenhouse gases considerably – together making these diets efficient means [moving] towards a more sustainable development, while at the same time reducing the growing burden of atherosclerotic cardiovascular disease.”
More support for vegan, vegetarian diets
These new findings “add to the body of evidence supporting favorable effects of healthy vegan and vegetarian dietary patterns on circulating levels of LDL-C and atherogenic lipoproteins, which would be expected to reduce ASCVD risk,” Kevin C. Maki, PhD, and Carol Kirkpatrick, PhD, MPH, write in an accompanying editorial.
“While it is not necessary to entirely omit foods such as meat, poultry, and fish/seafood to follow a recommended dietary pattern, reducing consumption of such foods is a reasonable option for those who prefer to do so,” note Dr. Maki, of Indiana University School of Public Health, Bloomington, and Kirkpatrick, of Idaho State University, Pocatello.
Plant-based diet needs to be ‘well-planned’
Several experts who were not involved in this meta-analysis shed light on the study and its implications in comments to the U.K. Science Media Center.
“Although a vegetarian and vegan diet can be very healthy and beneficial with respect to cardiovascular risk, it is important that it is well planned so that nutrients it can be low in are included, including iron, iodine, vitamin B12, and vitamin D,” said Duane Mellor, PhD, a registered dietitian and senior lecturer, Aston Medical School, Aston University, Birmingham, England.
Some people “may find it easier to follow a Mediterranean-style diet that features plenty of fruit, vegetables, pulses, wholegrains, fish, eggs and low-fat dairy, with only small amounts of meat,” Tracy Parker, senior dietitian at the British Heart Foundation, London, suggested.
“There is considerable evidence that this type of diet can help lower your risk of developing heart and circulatory diseases by improving cholesterol and blood pressure levels, reducing inflammation, and controlling blood glucose levels,” she added.
And Aedin Cassidy, PhD, chair in nutrition & preventative medicine, Queen’s University Belfast (Ireland), noted that “not all plant-based diets are equal. Healthy plant-based diets, characterized by fruits, vegetables, and whole grains improve health, but other plant diets (for example, those including refined carbohydrates, processed foods high in fat/salt, etc.) do not.”
This new study shows that plant-based diets have the potential to improve health by improving blood lipids, “but this is one of many potential mechanisms, including impact on blood pressure, weight maintenance, and blood sugars,” she added.
“This work represents a well-conducted analysis of 30 clinical trials involving over two thousand participants and highlights the value of a vegetarian diet in reducing the risk of heart attack or stroke through reduction in blood cholesterol levels,” said Robert Storey, BM, DM, professor of cardiology, University of Sheffield, U.K.
However, it also demonstrates that the impact of diet on an individual’s cholesterol level is relatively limited, he added.
“This is because people inherit the tendency for their livers to produce too much cholesterol, meaning that high cholesterol is more strongly influenced by our genes than by our diet,” he explained.
This is “why statins are needed to block cholesterol production in people who are at higher risk of or have already suffered from a heart attack, stroke, or other illness related to cholesterol build-up in blood vessels.”
Beneficial effect on ApoB, LDL-C, and total cholesterol
ApoB is the main apolipoprotein in LDL-C (“bad” cholesterol), the researchers note. Previous studies have shown that LDL-C and apoB-containing particles are associated with increased risk of ASCVD.
They aimed to estimate the effect of vegetarian or vegan diets on blood levels of total cholesterol, LDL-C, triglycerides, and apoB in people randomized to a vegetarian or vegan diet versus an omnivorous diet (that is, including meat and dairy).
They identified 30 studies published between 1982 and 2022 and conducted in the United States (18 studies), Sweden (2), Finland (2), South Korea (2), Australia (1), Brazil (1), Czech Republic (1), Italy (1), Iran (1), and New Zealand (1).
The diet interventions lasted from 10 days to 5 years with a mean of 29 weeks (15 studies ≤ 3 months; 12 studies 3-12 months; and three studies > 1 year). Nine studies used a crossover design, and the rest used a parallel design whereby participants followed only one diet.
The studies had 11 to 291 participants (mean, 79 participants) with a mean BMI of 21.5-35.1 kg/m2 and a mean age of 20-67 years. Thirteen studies included participants treated with lipid-lowering therapy at baseline.
The dietary intervention was vegetarian in 15 trials (three lacto-vegetarian and 12 lacto-ovo-vegetarian) and vegan in the other 15 trials.
On average, compared with people eating an omnivore diet, people eating a plant-based diet had a 7% reduction in total cholesterol from baseline (–0.34 mmol/L), a 10% reduction in LDL-C from baseline (–0.30 mmol/L), and a 14% reduction in apoB from baseline (–12.9 mg/dL) (all P < .01).
The effects were similar across age, continent, study duration, health status, intervention diet, intervention program, and study design subgroups.
There was no significant difference in triglyceride levels in patients in the omnivore versus plant-based diet groups.
Such diets could considerably reduce greenhouse gases
Senior author Dr. Frikke-Schmidt noted: “Recent systematic reviews have shown that if the populations of high-income countries shift to plant-based diets, this can reduce net emissions of greenhouse gases by between 35% to 49%.”
“Plant-based diets are key instruments for changing food production to more environmentally sustainable forms, while at the same time reducing the burden of cardiovascular disease” in an aging population, she said.
“We should be eating a varied, plant-rich diet, not too much, and quenching our thirst with water,” she concluded.
The study was funded by the Lundbeck Foundation, the Danish Heart Foundation, and the Leducq Foundation. The authors, editorialists, Ms. Parker, Dr. Cassidy, and Dr. Storey have reported no relevant financial relationships. Dr. Mellor has disclosed that he is a vegetarian.
A version of this article first appeared on Medscape.com.
FROM EUROPEAN HEART JOURNAL
Circulatory support for RV failure caused by pulmonary embolism
A new review article highlights approaches for mechanical circulatory support in patients with high-risk acute pulmonary embolism (PE).
Pulmonary embolism with hemodynamic significance is widely underdiagnosed, and the mortality rate can be as high as 30%, but new therapeutic developments offer promise. “Over the past few years, a renewed interest in mechanical circulatory support (MCS; both percutaneous and surgical) for acute RVF has emerged, increasing viable treatment options for high-risk acute PE,” wrote the authors of the review, which was published online in Interventional Cardiology Clinics.
Poor outcomes are often driven by RVF, which is tricky to diagnose and manage, and it stems from a sudden increase in pulmonary vascular resistance (PVR) following PE. “The mechanism for increased PVR in acute PE is multifactorial, including direct blood flow impedance, local hypoxia-induced vasoconstriction, and platelet/thrombin-induced release of vasoactive peptides. The cascade of events that then leads to RVF includes decreased RV stoke volume, increased RV wall tension, and RV dilation,” the authors wrote.
The authors noted that diuretics help to correct changes to RV geometry and can improve left ventricle filling, which improves hemodynamics. Diuretics can be used in patients who are hypotensive and volume overloaded, but vasopressors should be employed to support blood pressure.
When using mechanical ventilation, strategies such as low tidal volumes, minimization of positive end expiratory pressure, and prevention of hypoxemia and acidemia should be employed to prevent an increase of pulmonary vascular resistance, which can worsen RV failure.
Pulmonary vasodilators aren’t recommended for acute PE, but inhaled pulmonary vasodilators may be considered in hemodynamically unstable patients.
Surgically implanted right ventricle assistance device are generally not used for acute RV failure in high-risk PE, unless the patient has not improved after medical management.
Percutaneous devices
Percutaneous mechanical circulatory support devices can be used for patients experiencing refractory shock. The review highlighted three such devices, including the Impella RP, tandem-heart right ventricular assist devices (TH-RVAD) or Protek Duo, and venoarterial extracorporeal membrane oxygenation (VA-ECMO), but they are not without limitations. “Challenges to using these devices in patients with acute PE include clot dislodgement, vascular complications, infections, device migration, and fracture of individual elements,” the authors wrote.
The Impella RP is easy to deploy and bypasses the RV, but it can’t provide blood oxygenation and may cause bleeding or hemolysis. TH-RVAD oxygenates the blood and bypasses the RV, but suffers from a large sheath size. VA-ECMO oxygenates the blood but may cause bleeding.
There are important differences among the mechanical support devices, according to Jonathan Ludmir, MD, who was asked to comment. “In reality, if someone has a large pulmonary embolism burden, to put in the Impella RP or the Protek Duo would be a little bit risky, because you’d be sometimes putting the device right where the clot is. At least what we do in our institution, when someone is in extremis despite using [intravenous] medications like vasopressors or inotropes, VA-ECMO is kind of the go to. This is both the quickest and probably most effective way to support the patient. I say the quickest because this is a procedure you can do at the bedside.”
Benefits of PERT
One message that the review only briefly mentions, but Dr. Ludmir believes is key, is employing a pulmonary embolism response team. “That’s been looked at extensively, and it’s a really key part of any decision-making. If someone presents to the emergency room or someone inside the hospital has an acute pulmonary embolism, you have a team of people that can respond and help assess the next step. Typically, that involves a cardiologist or an interventional cardiologist, a hematologist, vascular surgeon, often a cardiac surgeon, so it’s a whole slew of people. Based on the patient assessment they can quickly decide, can this patient just be okay with a blood thinner like heparin? Does this patient need something more aggressive, like a thrombectomy? Or is this a serious case where you involve the shock team or the ECMO team, and you have to stabilize the patient on mechanical circulatory support, so you can accomplish what you need to do to get rid of the pulmonary embolism,” said Dr. Ludmir, who is an assistant professor of medicine at Corrigan Minehan Heart Center at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“Every case is individualized, hence the importance of having a team of a variety of different backgrounds and thoughts to approach it. And I think that’s kind of like the key takeaway. Yes, you have to be familiar with all the therapies, but at the end of the day, not every patient is going to fit into the algorithm for how you approach pulmonary embolism,” said Dr. Ludmir.
Dr. Ludmir has no relevant conflicts of interest.
A new review article highlights approaches for mechanical circulatory support in patients with high-risk acute pulmonary embolism (PE).
Pulmonary embolism with hemodynamic significance is widely underdiagnosed, and the mortality rate can be as high as 30%, but new therapeutic developments offer promise. “Over the past few years, a renewed interest in mechanical circulatory support (MCS; both percutaneous and surgical) for acute RVF has emerged, increasing viable treatment options for high-risk acute PE,” wrote the authors of the review, which was published online in Interventional Cardiology Clinics.
Poor outcomes are often driven by RVF, which is tricky to diagnose and manage, and it stems from a sudden increase in pulmonary vascular resistance (PVR) following PE. “The mechanism for increased PVR in acute PE is multifactorial, including direct blood flow impedance, local hypoxia-induced vasoconstriction, and platelet/thrombin-induced release of vasoactive peptides. The cascade of events that then leads to RVF includes decreased RV stoke volume, increased RV wall tension, and RV dilation,” the authors wrote.
The authors noted that diuretics help to correct changes to RV geometry and can improve left ventricle filling, which improves hemodynamics. Diuretics can be used in patients who are hypotensive and volume overloaded, but vasopressors should be employed to support blood pressure.
When using mechanical ventilation, strategies such as low tidal volumes, minimization of positive end expiratory pressure, and prevention of hypoxemia and acidemia should be employed to prevent an increase of pulmonary vascular resistance, which can worsen RV failure.
Pulmonary vasodilators aren’t recommended for acute PE, but inhaled pulmonary vasodilators may be considered in hemodynamically unstable patients.
Surgically implanted right ventricle assistance device are generally not used for acute RV failure in high-risk PE, unless the patient has not improved after medical management.
Percutaneous devices
Percutaneous mechanical circulatory support devices can be used for patients experiencing refractory shock. The review highlighted three such devices, including the Impella RP, tandem-heart right ventricular assist devices (TH-RVAD) or Protek Duo, and venoarterial extracorporeal membrane oxygenation (VA-ECMO), but they are not without limitations. “Challenges to using these devices in patients with acute PE include clot dislodgement, vascular complications, infections, device migration, and fracture of individual elements,” the authors wrote.
The Impella RP is easy to deploy and bypasses the RV, but it can’t provide blood oxygenation and may cause bleeding or hemolysis. TH-RVAD oxygenates the blood and bypasses the RV, but suffers from a large sheath size. VA-ECMO oxygenates the blood but may cause bleeding.
There are important differences among the mechanical support devices, according to Jonathan Ludmir, MD, who was asked to comment. “In reality, if someone has a large pulmonary embolism burden, to put in the Impella RP or the Protek Duo would be a little bit risky, because you’d be sometimes putting the device right where the clot is. At least what we do in our institution, when someone is in extremis despite using [intravenous] medications like vasopressors or inotropes, VA-ECMO is kind of the go to. This is both the quickest and probably most effective way to support the patient. I say the quickest because this is a procedure you can do at the bedside.”
Benefits of PERT
One message that the review only briefly mentions, but Dr. Ludmir believes is key, is employing a pulmonary embolism response team. “That’s been looked at extensively, and it’s a really key part of any decision-making. If someone presents to the emergency room or someone inside the hospital has an acute pulmonary embolism, you have a team of people that can respond and help assess the next step. Typically, that involves a cardiologist or an interventional cardiologist, a hematologist, vascular surgeon, often a cardiac surgeon, so it’s a whole slew of people. Based on the patient assessment they can quickly decide, can this patient just be okay with a blood thinner like heparin? Does this patient need something more aggressive, like a thrombectomy? Or is this a serious case where you involve the shock team or the ECMO team, and you have to stabilize the patient on mechanical circulatory support, so you can accomplish what you need to do to get rid of the pulmonary embolism,” said Dr. Ludmir, who is an assistant professor of medicine at Corrigan Minehan Heart Center at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“Every case is individualized, hence the importance of having a team of a variety of different backgrounds and thoughts to approach it. And I think that’s kind of like the key takeaway. Yes, you have to be familiar with all the therapies, but at the end of the day, not every patient is going to fit into the algorithm for how you approach pulmonary embolism,” said Dr. Ludmir.
Dr. Ludmir has no relevant conflicts of interest.
A new review article highlights approaches for mechanical circulatory support in patients with high-risk acute pulmonary embolism (PE).
Pulmonary embolism with hemodynamic significance is widely underdiagnosed, and the mortality rate can be as high as 30%, but new therapeutic developments offer promise. “Over the past few years, a renewed interest in mechanical circulatory support (MCS; both percutaneous and surgical) for acute RVF has emerged, increasing viable treatment options for high-risk acute PE,” wrote the authors of the review, which was published online in Interventional Cardiology Clinics.
Poor outcomes are often driven by RVF, which is tricky to diagnose and manage, and it stems from a sudden increase in pulmonary vascular resistance (PVR) following PE. “The mechanism for increased PVR in acute PE is multifactorial, including direct blood flow impedance, local hypoxia-induced vasoconstriction, and platelet/thrombin-induced release of vasoactive peptides. The cascade of events that then leads to RVF includes decreased RV stoke volume, increased RV wall tension, and RV dilation,” the authors wrote.
The authors noted that diuretics help to correct changes to RV geometry and can improve left ventricle filling, which improves hemodynamics. Diuretics can be used in patients who are hypotensive and volume overloaded, but vasopressors should be employed to support blood pressure.
When using mechanical ventilation, strategies such as low tidal volumes, minimization of positive end expiratory pressure, and prevention of hypoxemia and acidemia should be employed to prevent an increase of pulmonary vascular resistance, which can worsen RV failure.
Pulmonary vasodilators aren’t recommended for acute PE, but inhaled pulmonary vasodilators may be considered in hemodynamically unstable patients.
Surgically implanted right ventricle assistance device are generally not used for acute RV failure in high-risk PE, unless the patient has not improved after medical management.
Percutaneous devices
Percutaneous mechanical circulatory support devices can be used for patients experiencing refractory shock. The review highlighted three such devices, including the Impella RP, tandem-heart right ventricular assist devices (TH-RVAD) or Protek Duo, and venoarterial extracorporeal membrane oxygenation (VA-ECMO), but they are not without limitations. “Challenges to using these devices in patients with acute PE include clot dislodgement, vascular complications, infections, device migration, and fracture of individual elements,” the authors wrote.
The Impella RP is easy to deploy and bypasses the RV, but it can’t provide blood oxygenation and may cause bleeding or hemolysis. TH-RVAD oxygenates the blood and bypasses the RV, but suffers from a large sheath size. VA-ECMO oxygenates the blood but may cause bleeding.
There are important differences among the mechanical support devices, according to Jonathan Ludmir, MD, who was asked to comment. “In reality, if someone has a large pulmonary embolism burden, to put in the Impella RP or the Protek Duo would be a little bit risky, because you’d be sometimes putting the device right where the clot is. At least what we do in our institution, when someone is in extremis despite using [intravenous] medications like vasopressors or inotropes, VA-ECMO is kind of the go to. This is both the quickest and probably most effective way to support the patient. I say the quickest because this is a procedure you can do at the bedside.”
Benefits of PERT
One message that the review only briefly mentions, but Dr. Ludmir believes is key, is employing a pulmonary embolism response team. “That’s been looked at extensively, and it’s a really key part of any decision-making. If someone presents to the emergency room or someone inside the hospital has an acute pulmonary embolism, you have a team of people that can respond and help assess the next step. Typically, that involves a cardiologist or an interventional cardiologist, a hematologist, vascular surgeon, often a cardiac surgeon, so it’s a whole slew of people. Based on the patient assessment they can quickly decide, can this patient just be okay with a blood thinner like heparin? Does this patient need something more aggressive, like a thrombectomy? Or is this a serious case where you involve the shock team or the ECMO team, and you have to stabilize the patient on mechanical circulatory support, so you can accomplish what you need to do to get rid of the pulmonary embolism,” said Dr. Ludmir, who is an assistant professor of medicine at Corrigan Minehan Heart Center at Massachusetts General Hospital and Harvard Medical School, both in Boston.
“Every case is individualized, hence the importance of having a team of a variety of different backgrounds and thoughts to approach it. And I think that’s kind of like the key takeaway. Yes, you have to be familiar with all the therapies, but at the end of the day, not every patient is going to fit into the algorithm for how you approach pulmonary embolism,” said Dr. Ludmir.
Dr. Ludmir has no relevant conflicts of interest.
FROM INTERVENTIONAL CARDIOLOGY CLINICS