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Calcium burden drives CV risk whether coronary disease is obstructive or not
Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.
Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).
The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.
The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.
“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.
The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”
In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”
The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.
Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.
The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.
“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”
Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”
In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.
About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.
The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.
The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.
The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.
And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.
The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.
However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.
Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.
“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.
The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”
Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”
An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”
But they pointed out some limitations of the current study.
“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”
The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”
Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.
A version of this article originally appeared on Medscape.com.
Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.
Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).
The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.
The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.
“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.
The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”
In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”
The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.
Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.
The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.
“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”
Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”
In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.
About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.
The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.
The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.
The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.
And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.
The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.
However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.
Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.
“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.
The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”
Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”
An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”
But they pointed out some limitations of the current study.
“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”
The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”
Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.
A version of this article originally appeared on Medscape.com.
Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.
Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).
The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.
The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.
“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.
The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”
In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”
The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.
Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.
The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.
“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”
Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”
In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.
About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.
The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.
The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.
The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.
And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.
The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.
However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.
Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.
“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.
The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”
Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”
An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”
But they pointed out some limitations of the current study.
“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”
The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”
Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.
A version of this article originally appeared on Medscape.com.
Study results support screening rosacea patients for cardiometabolic disease
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
according to the results of a meta-analysis of more than 50,000 patients.
To date, “mounting comorbidities of rosacea have been identified, suggesting that rosacea is not simply a skin disease but has links to multiple systemic illnesses,” wrote Qi Chen, MD, of Central South University, Changsha, China, and colleagues. The association with rosacea and cardiometabolic disease has been controversial, they added.
In a study published in the Journal of the American Academy of Dermatology, they identified 13 studies including 50,442 rosacea patients and 1,525,864 controls. Approximately 71% of the rosacea patients were women.
Overall, patients with rosacea showed a statistically significant association for hypertension (risk ratio, 1.20; 95% confidence interval, 1.08-1.34; P = .001) and dyslipidemia (RR, 1.32; 95% CI, 1.10-1.58; P = .002). Specifically, rosacea patients averaged higher standard mean differences of systolic and diastolic blood pressure, total cholesterol, HDL cholesterol and LDL cholesterol, and triglycerides, compared with controls.
Rosacea was not significantly associated with an increased risk for ischemic heart disease, stroke, or diabetes, although the rosacea patients showed significantly increased risk of higher fasting blood glucose, compared with controls.
Findings don’t show causality
The study findings were limited by several factors, including the observational nature of some of the studies and the inability to perform subgroup analyses based on subtype and disease severity, the researchers noted. In addition, most of the rosacea patients were outpatients. “Further investigations are warranted to identify the relationship between rosacea and [cardiometabolic disease] in general populations to further validate the significance of our findings.”
However, the results support the value of screening for cardiometabolic disease in rosacea patients to facilitate diagnosis and treatment of disease at an early stage, they concluded.
“Rosacea has been linked statistically to many comorbidities including depression, anxiety, hypertension, and diabetes mellitus,” Julie Harper, MD, of the Dermatology and Skin Care Center of Birmingham (Alabama), said in an interview.
“This study looked more specifically at cardiometabolic disease and found a statistically significant correlation between rosacea and hypertension, higher total cholesterol, higher triglycerides and higher fasting blood glucose,” she said. However, “while there is an association present in this meta-analysis, we cannot assume a cause-and-effect relationship.”
Although the analysis does not prove causality, the key message for clinicians is that cardiometabolic disease is quite common in rosacea patients, and risk factors should be identified and treated early, said Dr. Harper. “Our patients with and without rosacea will benefit from age-appropriate screening, physical examination, and laboratory evaluation with a primary care physician. For rosacea patients in particular, we can advise them that early research suggests that individuals with rosacea might have an increased risk of hypertension and/or high cholesterol and triglycerides. It never hurts to make an appointment with primary care and to be checked.”
“We need more confirmatory studies that minimize the influence of confounding,” Dr. Harper added. Rosacea also has also been linked to obesity, which is another risk factor for cardiometabolic disease.
The study was supported by multiple grants from the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose. Dr. Harper had no relevant financial conflicts to disclose.
SOURCE: Chen Q et al. J Am Acad Dermatol. 2020 Nov;83(5):1331-40.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Major depression linked to insulin resistance
Individuals experiencing a current episode of major depressive disorder (MDD) are significantly more likely to have insulin resistance (IR), research shows.
Investigators found patients with MDD were 51% more likely to have IR, compared with their counterparts without depressive disorder. In addition, in individuals experiencing current depression, IR was also associated with depression severity and depression chronicity.
“We learned two things from this study – first, that insulin resistance was associated with being in a depressive episode and with the severity of that episode,” Kathleen Watson, PhD, a postdoctoral research fellow in the department of psychiatry, Stanford (Calif.) University, told this news organization. “Second, we learned that we can estimate insulin resistance using a surrogate measure that is clinically accessible – the triglyceride/HDL ratio.”
The study was published online Dec. 2 in JAMA Psychiatry.
Targeted approach
Many studies have linked MDD and IR. However, said Dr. Watson, “We did not have much description of the nature of this relationship.” She added that her team wanted to gain a better understanding of how IR relates to depression characteristics, such as remission status, severity, and chronicity.
Characterizing these associations will “represent a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD,” the authors note.
For the study, the researchers drew on data from the Netherlands Study of Depression and Anxiety, a longitudinal Dutch study of adults that “describes the course and consequences of depressive and anxiety disorders.”
The study included 1,269 study participants with current MDD (n = 536), remitted MDD (n = 394), and control participants without a history of MDD (n = 339).
In addition to investigating the association between MDD and IR, the researchers also wanted to understand “whether using different surrogate IR measures has consistent association with MDD.” IR was determined using two surrogate markers – the quantitative insulin sensitivity check index (QUICKI) and the triglyceride to high-density lipoprotein ratio. Participants in the bottom quartile of the QUICKI were categorized as IR, while all other participants were categorized as being “insulin sensitive.”
The second surrogate IR measure – the triglyceride-HDL ratio – is an index based on fasting blood sample measurements, in which the determination of IR was based on sex-specific cut points (female ratio, IR > 1.9; male ratio, IR > 2.8).
Depression was determined based on the Composite International Diagnostic Interview (version 2.1), while depression severity was based on the Inventory of Depression Symptomatology. “Chronicity” was defined as depression during the preceding 4 years and was measured using the life chart review.
State vs. trait
Insulin resistance was associated with current, but not with remitted, MDD (odds ratio, 1.51; 95% confidence interval, 1.08-2.12 and OR, 1.14; 95% CI, 0.79-1.64, respectively).
In a model adjusted for age, sex, education, partner status, smoking status, and alcohol consumption, IR, as assessed by both measures, was linked to depression severity – but only the triglyceride-HDL ratio yielded an association between IR and depression chronicity.
IR was not associated with depression severity or chronicity in remitted MDD on either measure.
The findings – specifically the association between current, but not remitted, MDD – suggest that “IR is a state, rather than a trait, biomarker of depression,” the authors note.
“There are many plausible mechanisms between IR and MDD,” said Dr. Watson. “Some hypotheses for the link include inflammations, alterations to the hypothalamic-pituitary-adrenal axis, and changes in health behavior.
“Understanding these nuances helped us to lay the foundation for future research, including asking whether IR can lead to the development of MDD,” she added.
Finally, and ways to target them with potential treatments or interventions.
Shared biological mechanisms?
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto and head of the Mood Disorders Psychopharmacology Unit, said the results “suggest that a subpopulation of people with depression have what might be referred to as ‘metabolic syndrome type II’ – the depression is a consequence of abnormal metabolic processes.”
The results also suggest “maybe metabolic markers can be used as biomarkers of disease presence vs. absence,” said Dr. McIntyre, who is also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, and was not involved with the study.
Also commenting on the study, Andrea Fagiolini, MD, professor of psychiatry, University of Siena (Italy), said depression, metabolic, and inflammatory diseases “likely share some common biological mechanism, as they share risk factors such as unhealthy diet, unhealthy lifestyles, and frequent exposure to physical and psychological distress.”
It is “possible that treatment of depression improves IR; conversely, it is possible that lifestyle programs or medications that are able to improve IR may improve depressive symptoms,” suggested Dr. Fagiolini, who was not involved with the study. “It remains to be established which symptoms of depression are most involved in this correlation and whether their improvement precedes or follows the improvement in IR,” he noted.
The Netherlands Study of Depression and Anxiety is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development and is supported by several participating universities and mental health care organizations. Dr. Watson has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reported research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from multiple pharmaceutical companies. Dr. McIntyre is also CEO of AltMed. Dr. Fagiolini has served or is currently serving as consultant or speaker for or is a research grant recipient from multiple pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
Individuals experiencing a current episode of major depressive disorder (MDD) are significantly more likely to have insulin resistance (IR), research shows.
Investigators found patients with MDD were 51% more likely to have IR, compared with their counterparts without depressive disorder. In addition, in individuals experiencing current depression, IR was also associated with depression severity and depression chronicity.
“We learned two things from this study – first, that insulin resistance was associated with being in a depressive episode and with the severity of that episode,” Kathleen Watson, PhD, a postdoctoral research fellow in the department of psychiatry, Stanford (Calif.) University, told this news organization. “Second, we learned that we can estimate insulin resistance using a surrogate measure that is clinically accessible – the triglyceride/HDL ratio.”
The study was published online Dec. 2 in JAMA Psychiatry.
Targeted approach
Many studies have linked MDD and IR. However, said Dr. Watson, “We did not have much description of the nature of this relationship.” She added that her team wanted to gain a better understanding of how IR relates to depression characteristics, such as remission status, severity, and chronicity.
Characterizing these associations will “represent a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD,” the authors note.
For the study, the researchers drew on data from the Netherlands Study of Depression and Anxiety, a longitudinal Dutch study of adults that “describes the course and consequences of depressive and anxiety disorders.”
The study included 1,269 study participants with current MDD (n = 536), remitted MDD (n = 394), and control participants without a history of MDD (n = 339).
In addition to investigating the association between MDD and IR, the researchers also wanted to understand “whether using different surrogate IR measures has consistent association with MDD.” IR was determined using two surrogate markers – the quantitative insulin sensitivity check index (QUICKI) and the triglyceride to high-density lipoprotein ratio. Participants in the bottom quartile of the QUICKI were categorized as IR, while all other participants were categorized as being “insulin sensitive.”
The second surrogate IR measure – the triglyceride-HDL ratio – is an index based on fasting blood sample measurements, in which the determination of IR was based on sex-specific cut points (female ratio, IR > 1.9; male ratio, IR > 2.8).
Depression was determined based on the Composite International Diagnostic Interview (version 2.1), while depression severity was based on the Inventory of Depression Symptomatology. “Chronicity” was defined as depression during the preceding 4 years and was measured using the life chart review.
State vs. trait
Insulin resistance was associated with current, but not with remitted, MDD (odds ratio, 1.51; 95% confidence interval, 1.08-2.12 and OR, 1.14; 95% CI, 0.79-1.64, respectively).
In a model adjusted for age, sex, education, partner status, smoking status, and alcohol consumption, IR, as assessed by both measures, was linked to depression severity – but only the triglyceride-HDL ratio yielded an association between IR and depression chronicity.
IR was not associated with depression severity or chronicity in remitted MDD on either measure.
The findings – specifically the association between current, but not remitted, MDD – suggest that “IR is a state, rather than a trait, biomarker of depression,” the authors note.
“There are many plausible mechanisms between IR and MDD,” said Dr. Watson. “Some hypotheses for the link include inflammations, alterations to the hypothalamic-pituitary-adrenal axis, and changes in health behavior.
“Understanding these nuances helped us to lay the foundation for future research, including asking whether IR can lead to the development of MDD,” she added.
Finally, and ways to target them with potential treatments or interventions.
Shared biological mechanisms?
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto and head of the Mood Disorders Psychopharmacology Unit, said the results “suggest that a subpopulation of people with depression have what might be referred to as ‘metabolic syndrome type II’ – the depression is a consequence of abnormal metabolic processes.”
The results also suggest “maybe metabolic markers can be used as biomarkers of disease presence vs. absence,” said Dr. McIntyre, who is also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, and was not involved with the study.
Also commenting on the study, Andrea Fagiolini, MD, professor of psychiatry, University of Siena (Italy), said depression, metabolic, and inflammatory diseases “likely share some common biological mechanism, as they share risk factors such as unhealthy diet, unhealthy lifestyles, and frequent exposure to physical and psychological distress.”
It is “possible that treatment of depression improves IR; conversely, it is possible that lifestyle programs or medications that are able to improve IR may improve depressive symptoms,” suggested Dr. Fagiolini, who was not involved with the study. “It remains to be established which symptoms of depression are most involved in this correlation and whether their improvement precedes or follows the improvement in IR,” he noted.
The Netherlands Study of Depression and Anxiety is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development and is supported by several participating universities and mental health care organizations. Dr. Watson has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reported research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from multiple pharmaceutical companies. Dr. McIntyre is also CEO of AltMed. Dr. Fagiolini has served or is currently serving as consultant or speaker for or is a research grant recipient from multiple pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
Individuals experiencing a current episode of major depressive disorder (MDD) are significantly more likely to have insulin resistance (IR), research shows.
Investigators found patients with MDD were 51% more likely to have IR, compared with their counterparts without depressive disorder. In addition, in individuals experiencing current depression, IR was also associated with depression severity and depression chronicity.
“We learned two things from this study – first, that insulin resistance was associated with being in a depressive episode and with the severity of that episode,” Kathleen Watson, PhD, a postdoctoral research fellow in the department of psychiatry, Stanford (Calif.) University, told this news organization. “Second, we learned that we can estimate insulin resistance using a surrogate measure that is clinically accessible – the triglyceride/HDL ratio.”
The study was published online Dec. 2 in JAMA Psychiatry.
Targeted approach
Many studies have linked MDD and IR. However, said Dr. Watson, “We did not have much description of the nature of this relationship.” She added that her team wanted to gain a better understanding of how IR relates to depression characteristics, such as remission status, severity, and chronicity.
Characterizing these associations will “represent a critical step at better phenotyping, a prelude to longitudinal studies, and a more targeted approach to the treatment of MDD,” the authors note.
For the study, the researchers drew on data from the Netherlands Study of Depression and Anxiety, a longitudinal Dutch study of adults that “describes the course and consequences of depressive and anxiety disorders.”
The study included 1,269 study participants with current MDD (n = 536), remitted MDD (n = 394), and control participants without a history of MDD (n = 339).
In addition to investigating the association between MDD and IR, the researchers also wanted to understand “whether using different surrogate IR measures has consistent association with MDD.” IR was determined using two surrogate markers – the quantitative insulin sensitivity check index (QUICKI) and the triglyceride to high-density lipoprotein ratio. Participants in the bottom quartile of the QUICKI were categorized as IR, while all other participants were categorized as being “insulin sensitive.”
The second surrogate IR measure – the triglyceride-HDL ratio – is an index based on fasting blood sample measurements, in which the determination of IR was based on sex-specific cut points (female ratio, IR > 1.9; male ratio, IR > 2.8).
Depression was determined based on the Composite International Diagnostic Interview (version 2.1), while depression severity was based on the Inventory of Depression Symptomatology. “Chronicity” was defined as depression during the preceding 4 years and was measured using the life chart review.
State vs. trait
Insulin resistance was associated with current, but not with remitted, MDD (odds ratio, 1.51; 95% confidence interval, 1.08-2.12 and OR, 1.14; 95% CI, 0.79-1.64, respectively).
In a model adjusted for age, sex, education, partner status, smoking status, and alcohol consumption, IR, as assessed by both measures, was linked to depression severity – but only the triglyceride-HDL ratio yielded an association between IR and depression chronicity.
IR was not associated with depression severity or chronicity in remitted MDD on either measure.
The findings – specifically the association between current, but not remitted, MDD – suggest that “IR is a state, rather than a trait, biomarker of depression,” the authors note.
“There are many plausible mechanisms between IR and MDD,” said Dr. Watson. “Some hypotheses for the link include inflammations, alterations to the hypothalamic-pituitary-adrenal axis, and changes in health behavior.
“Understanding these nuances helped us to lay the foundation for future research, including asking whether IR can lead to the development of MDD,” she added.
Finally, and ways to target them with potential treatments or interventions.
Shared biological mechanisms?
Commenting on the study in an interview, Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto and head of the Mood Disorders Psychopharmacology Unit, said the results “suggest that a subpopulation of people with depression have what might be referred to as ‘metabolic syndrome type II’ – the depression is a consequence of abnormal metabolic processes.”
The results also suggest “maybe metabolic markers can be used as biomarkers of disease presence vs. absence,” said Dr. McIntyre, who is also the chairman and executive director of the Brain and Cognition Discovery Foundation, Toronto, and was not involved with the study.
Also commenting on the study, Andrea Fagiolini, MD, professor of psychiatry, University of Siena (Italy), said depression, metabolic, and inflammatory diseases “likely share some common biological mechanism, as they share risk factors such as unhealthy diet, unhealthy lifestyles, and frequent exposure to physical and psychological distress.”
It is “possible that treatment of depression improves IR; conversely, it is possible that lifestyle programs or medications that are able to improve IR may improve depressive symptoms,” suggested Dr. Fagiolini, who was not involved with the study. “It remains to be established which symptoms of depression are most involved in this correlation and whether their improvement precedes or follows the improvement in IR,” he noted.
The Netherlands Study of Depression and Anxiety is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development and is supported by several participating universities and mental health care organizations. Dr. Watson has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Dr. McIntyre reported research grant support from CIHR/GACD/Chinese National Natural Research Foundation and speaker/consultation fees from multiple pharmaceutical companies. Dr. McIntyre is also CEO of AltMed. Dr. Fagiolini has served or is currently serving as consultant or speaker for or is a research grant recipient from multiple pharmaceutical companies.
A version of this article originally appeared on Medscape.com.
Endoscopic intragastric balloon improved NASH parameters
Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.
Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.
Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”
In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m2. At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.
Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.
Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”
Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.
SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
Obesity a well-known risk factor for the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis, the latter of which is expected to become the leading indication for liver transplantation. As such addressing the steatosis in these patients is critical. A drop of even 5%-10% of total body weight with diet and exercise can result in significant improvement in liver disease.
In this article, Dr. Bazerbachi and colleagues work to advance the case for intragastric balloons as a successful treatment option for NAFLD. They performed a prospective, open-label study on 21 patients treated with an intragastric balloon for 6 months. Using gold-standard histology and noninvasive magnetic resonance elastography before and after therapy, they show significant improvement in NAFLD activity score (median change, 3 points; range, 1-4) over a short duration of treatment. Interestingly, the collection of the liver biopsy sample is done via endoscopic ultrasound, which can be easily performed during placement and removal of this intragastric balloon. While promising, follow-up studies are needed to show sustained improvement in NAFLD after the balloon is removed.
Wasif M. Abidi, MD, PhD, is assistant professor of medicine, gastroenterology, Baylor College of Medicine, Houston.
Obesity a well-known risk factor for the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis, the latter of which is expected to become the leading indication for liver transplantation. As such addressing the steatosis in these patients is critical. A drop of even 5%-10% of total body weight with diet and exercise can result in significant improvement in liver disease.
In this article, Dr. Bazerbachi and colleagues work to advance the case for intragastric balloons as a successful treatment option for NAFLD. They performed a prospective, open-label study on 21 patients treated with an intragastric balloon for 6 months. Using gold-standard histology and noninvasive magnetic resonance elastography before and after therapy, they show significant improvement in NAFLD activity score (median change, 3 points; range, 1-4) over a short duration of treatment. Interestingly, the collection of the liver biopsy sample is done via endoscopic ultrasound, which can be easily performed during placement and removal of this intragastric balloon. While promising, follow-up studies are needed to show sustained improvement in NAFLD after the balloon is removed.
Wasif M. Abidi, MD, PhD, is assistant professor of medicine, gastroenterology, Baylor College of Medicine, Houston.
Obesity a well-known risk factor for the development of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis, the latter of which is expected to become the leading indication for liver transplantation. As such addressing the steatosis in these patients is critical. A drop of even 5%-10% of total body weight with diet and exercise can result in significant improvement in liver disease.
In this article, Dr. Bazerbachi and colleagues work to advance the case for intragastric balloons as a successful treatment option for NAFLD. They performed a prospective, open-label study on 21 patients treated with an intragastric balloon for 6 months. Using gold-standard histology and noninvasive magnetic resonance elastography before and after therapy, they show significant improvement in NAFLD activity score (median change, 3 points; range, 1-4) over a short duration of treatment. Interestingly, the collection of the liver biopsy sample is done via endoscopic ultrasound, which can be easily performed during placement and removal of this intragastric balloon. While promising, follow-up studies are needed to show sustained improvement in NAFLD after the balloon is removed.
Wasif M. Abidi, MD, PhD, is assistant professor of medicine, gastroenterology, Baylor College of Medicine, Houston.
Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.
Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.
Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”
In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m2. At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.
Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.
Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”
Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.
SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.
Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.
Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”
In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m2. At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.
Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.
Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”
Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.
SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
FDA clears first drug for rare genetic causes of severe obesity
The Food and Drug Administration has approved setmelanotide (Imcivree, Rhythm Pharmaceuticals) for weight management in adults and children as young as 6 years with obesity because of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.
Individuals with these rare genetic causes of severe obesity have a normal weight at birth but develop persistent severe obesity within months because of insatiable hunger (hyperphagia).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for these disorders.
“Many patients and families who live with these diseases face an often-burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, MD, a pediatric endocrinologist at University of Florida Health, Gainesville, in a press release issued by the company.
“This FDA approval marks an important turning point, providing a much needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity,” she noted.
David Meeker, MD, chair, president, and CEO of Rhythm Pharmaceuticals, added: “We are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the MC4R pathway.”
Setmelanotide was evaluated in two phase 3 clinical trials. In one trial, 80% of patients with obesity caused by POMC or PCSK1 deficiency achieved greater than 10% weight loss after 1 year of treatment.
In the other trial, 45.5% of patients with obesity caused by LEPR deficiency achieved greater than 10% weight loss with 1 year of treatment.
Results for the two trials were recently published in The Lancet Diabetes & Endocrinology and discussed at the ObesityWeek Interactive 2020 meeting.
Setmelanotide was generally well tolerated in both trials. The most common adverse events were injection-site reactions, skin hyperpigmentation, and nausea.
The drug label notes that disturbances in sexual arousal, depression, and suicidal ideation; skin pigmentation; and darkening of preexisting nevi may occur with setmelanotide treatment.
The drug label also notes a risk for serious adverse reactions because of benzyl alcohol preservative in neonates and low-birth-weight infants. Setmelanotide is not approved for use in neonates or infants.
The company expects the drug to be commercially available in the United States in the first quarter of 2021.
Setmelanotide for the treatment of obesity associated with rare genetic defects had FDA breakthrough therapy designation as well as orphan drug designation.
The company is also evaluating setmelanotide for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome, and top-line data are due soon.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has approved setmelanotide (Imcivree, Rhythm Pharmaceuticals) for weight management in adults and children as young as 6 years with obesity because of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.
Individuals with these rare genetic causes of severe obesity have a normal weight at birth but develop persistent severe obesity within months because of insatiable hunger (hyperphagia).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for these disorders.
“Many patients and families who live with these diseases face an often-burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, MD, a pediatric endocrinologist at University of Florida Health, Gainesville, in a press release issued by the company.
“This FDA approval marks an important turning point, providing a much needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity,” she noted.
David Meeker, MD, chair, president, and CEO of Rhythm Pharmaceuticals, added: “We are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the MC4R pathway.”
Setmelanotide was evaluated in two phase 3 clinical trials. In one trial, 80% of patients with obesity caused by POMC or PCSK1 deficiency achieved greater than 10% weight loss after 1 year of treatment.
In the other trial, 45.5% of patients with obesity caused by LEPR deficiency achieved greater than 10% weight loss with 1 year of treatment.
Results for the two trials were recently published in The Lancet Diabetes & Endocrinology and discussed at the ObesityWeek Interactive 2020 meeting.
Setmelanotide was generally well tolerated in both trials. The most common adverse events were injection-site reactions, skin hyperpigmentation, and nausea.
The drug label notes that disturbances in sexual arousal, depression, and suicidal ideation; skin pigmentation; and darkening of preexisting nevi may occur with setmelanotide treatment.
The drug label also notes a risk for serious adverse reactions because of benzyl alcohol preservative in neonates and low-birth-weight infants. Setmelanotide is not approved for use in neonates or infants.
The company expects the drug to be commercially available in the United States in the first quarter of 2021.
Setmelanotide for the treatment of obesity associated with rare genetic defects had FDA breakthrough therapy designation as well as orphan drug designation.
The company is also evaluating setmelanotide for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome, and top-line data are due soon.
A version of this article originally appeared on Medscape.com.
The Food and Drug Administration has approved setmelanotide (Imcivree, Rhythm Pharmaceuticals) for weight management in adults and children as young as 6 years with obesity because of proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing.
Individuals with these rare genetic causes of severe obesity have a normal weight at birth but develop persistent severe obesity within months because of insatiable hunger (hyperphagia).
Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is the first FDA-approved therapy for these disorders.
“Many patients and families who live with these diseases face an often-burdensome stigma associated with severe obesity. To manage this obesity and control disruptive food-seeking behavior, caregivers often lock cabinets and refrigerators and significantly limit social activities,” said Jennifer Miller, MD, a pediatric endocrinologist at University of Florida Health, Gainesville, in a press release issued by the company.
“This FDA approval marks an important turning point, providing a much needed therapy and supporting the use of genetic testing to identify and properly diagnose patients with these rare genetic diseases of obesity,” she noted.
David Meeker, MD, chair, president, and CEO of Rhythm Pharmaceuticals, added: “We are advancing a first-in-class, precision medicine that is designed to directly address the underlying cause of obesities driven by genetic deficits in the MC4R pathway.”
Setmelanotide was evaluated in two phase 3 clinical trials. In one trial, 80% of patients with obesity caused by POMC or PCSK1 deficiency achieved greater than 10% weight loss after 1 year of treatment.
In the other trial, 45.5% of patients with obesity caused by LEPR deficiency achieved greater than 10% weight loss with 1 year of treatment.
Results for the two trials were recently published in The Lancet Diabetes & Endocrinology and discussed at the ObesityWeek Interactive 2020 meeting.
Setmelanotide was generally well tolerated in both trials. The most common adverse events were injection-site reactions, skin hyperpigmentation, and nausea.
The drug label notes that disturbances in sexual arousal, depression, and suicidal ideation; skin pigmentation; and darkening of preexisting nevi may occur with setmelanotide treatment.
The drug label also notes a risk for serious adverse reactions because of benzyl alcohol preservative in neonates and low-birth-weight infants. Setmelanotide is not approved for use in neonates or infants.
The company expects the drug to be commercially available in the United States in the first quarter of 2021.
Setmelanotide for the treatment of obesity associated with rare genetic defects had FDA breakthrough therapy designation as well as orphan drug designation.
The company is also evaluating setmelanotide for reduction in hunger and body weight in a pivotal phase 3 trial in people living with Bardet-Biedl or Alström syndrome, and top-line data are due soon.
A version of this article originally appeared on Medscape.com.
Age no barrier to weight loss in those with morbid obesity
Older adults should be recommended for hospital-based lifestyle interventions to reduce weight, say U.K. investigators after finding there was no difference in weight loss between older and younger individuals in their program for those with morbid obesity.
Thomas M. Barber, PhD, and colleagues looked back at nearly 250 randomly selected adults who attended their obesity service over an 11-year period.
Older individuals, defined as aged 60 years and over, had higher rates of type 2 diabetes but experienced a similar percentage weight loss and reduction in body mass index (BMI) as younger patients over the course of around 40 months.
“Age should be no barrier to lifestyle management of obesity,” said Dr. Barber, of University Hospitals Coventry (England) and Warwickshire, in a news release from his institution. “Rather than putting up barriers to older people accessing weight-loss programs, we should be proactively facilitating that process. To do otherwise would risk further and unnecessary neglect of older people through societal ageist misconceptions.”
He urged service providers and policy makers to “appreciate the importance of weight loss in older people with obesity for the maintenance of health and well-being and the facilitation of healthy aging. Furthermore, age per se should not contribute toward clinical decisions regarding the implementation of lifestyle management of older people.”
The research was published online Nov. 22 in Clinical Endocrinology.
Real-world data will inform clinical practice
Jason Halford, PhD, a professor of biological psychology and health behavior, said in an interview: “The fear is that older patients are perceived not to respond” to lifestyle interventions to control obesity, “and that’s clearly a fallacy, according to this study.”
The findings are strengthened by the fact that these are real-world data, “and so it will inform clinical practice,” he added.
And one of the “more interesting” findings was that [type 2] diabetes was “more prevalent” in the older group “but they’re still losing weight,” he noted.
“Traditionally it’s been thought that people with type 2 diabetes find it more difficult to lose weight because you’re trying to manage two conditions,” said Dr. Halford, of the University of Leeds (England), who is also president-elect of the European Association for the Study of Obesity.
Don’t discount older patients
The researchers note that many of the comorbidities associated with obesity “develop over time” and that “no one is immune to obesity,” regardless of their age, sex, ethnicity, and socioeconomic status.
Barber said there are “a number of reasons” why health care professionals “may discount weight loss in older people,” including “an ‘ageist’ perspective that weight-loss is not relevant to older people and misconceptions of reduced ability of older people to lose weight through dietary modification and increased exercise.”
And “older people may feel that hospital-based obesity services are not for them,” he noted.
To determine the effect of age on the ability to lose weight through lifestyle interventions, Dr. Barber and colleagues randomly selected 242 patients with morbid obesity who attended their hospital-based service between 2005 and 2016.
Of these, 167 were aged 18-60 years and 75 were aged 60 years and older. Most participants were women (75.4% of the younger patients and 60.0% of the older patients).
The proportion of patients with confirmed diabetes was markedly higher in the older group, compared with the younger group, at 62.7% versus 35.3%, although older patients had a significantly lower baseline BMI, at 46.9 versus 49.7 kg/m2 (P < .05).
The average duration of the lifestyle intervention was over 3 years (41.5 months) in the younger patients and 33.6 months in the older patients.
There was no significant difference in percentage weight loss between younger and older patients, at 6.9% and 7.3%, respectively, and no difference in percentage reduction in BMI, at 8.1% versus 7.8%.
Further analysis demonstrated that there was no significant correlation between age at referral to the hospital-based service and percentage weight loss (correlation coefficient, –0.13).
Dr. Halford said it would have been “useful” to know the proportion of patients achieving 5% and 10% weight loss because, if a third of patients lost more than 10% of their weight, “even in an elderly population, that would suggest there’d be real benefits in terms of things like type 2 diabetes,” he noted.
And he would like to have seen more data around how long participants had been struggling with obesity, as it’s “just an assumption that the second group is further down the path because they’re older, but we can’t be 100% sure.”
The team noted the study is limited by being retrospective and including a random selection of patients attending the service rather than the entire cohort.
Dr. Halford agreed but said the analysis is a “starting point” and could be used as a platform to conduct “much more systematic research on this area.”
No funding or relevant financial relationships were declared.
A version of this article originally appeared on Medscape.com.
Older adults should be recommended for hospital-based lifestyle interventions to reduce weight, say U.K. investigators after finding there was no difference in weight loss between older and younger individuals in their program for those with morbid obesity.
Thomas M. Barber, PhD, and colleagues looked back at nearly 250 randomly selected adults who attended their obesity service over an 11-year period.
Older individuals, defined as aged 60 years and over, had higher rates of type 2 diabetes but experienced a similar percentage weight loss and reduction in body mass index (BMI) as younger patients over the course of around 40 months.
“Age should be no barrier to lifestyle management of obesity,” said Dr. Barber, of University Hospitals Coventry (England) and Warwickshire, in a news release from his institution. “Rather than putting up barriers to older people accessing weight-loss programs, we should be proactively facilitating that process. To do otherwise would risk further and unnecessary neglect of older people through societal ageist misconceptions.”
He urged service providers and policy makers to “appreciate the importance of weight loss in older people with obesity for the maintenance of health and well-being and the facilitation of healthy aging. Furthermore, age per se should not contribute toward clinical decisions regarding the implementation of lifestyle management of older people.”
The research was published online Nov. 22 in Clinical Endocrinology.
Real-world data will inform clinical practice
Jason Halford, PhD, a professor of biological psychology and health behavior, said in an interview: “The fear is that older patients are perceived not to respond” to lifestyle interventions to control obesity, “and that’s clearly a fallacy, according to this study.”
The findings are strengthened by the fact that these are real-world data, “and so it will inform clinical practice,” he added.
And one of the “more interesting” findings was that [type 2] diabetes was “more prevalent” in the older group “but they’re still losing weight,” he noted.
“Traditionally it’s been thought that people with type 2 diabetes find it more difficult to lose weight because you’re trying to manage two conditions,” said Dr. Halford, of the University of Leeds (England), who is also president-elect of the European Association for the Study of Obesity.
Don’t discount older patients
The researchers note that many of the comorbidities associated with obesity “develop over time” and that “no one is immune to obesity,” regardless of their age, sex, ethnicity, and socioeconomic status.
Barber said there are “a number of reasons” why health care professionals “may discount weight loss in older people,” including “an ‘ageist’ perspective that weight-loss is not relevant to older people and misconceptions of reduced ability of older people to lose weight through dietary modification and increased exercise.”
And “older people may feel that hospital-based obesity services are not for them,” he noted.
To determine the effect of age on the ability to lose weight through lifestyle interventions, Dr. Barber and colleagues randomly selected 242 patients with morbid obesity who attended their hospital-based service between 2005 and 2016.
Of these, 167 were aged 18-60 years and 75 were aged 60 years and older. Most participants were women (75.4% of the younger patients and 60.0% of the older patients).
The proportion of patients with confirmed diabetes was markedly higher in the older group, compared with the younger group, at 62.7% versus 35.3%, although older patients had a significantly lower baseline BMI, at 46.9 versus 49.7 kg/m2 (P < .05).
The average duration of the lifestyle intervention was over 3 years (41.5 months) in the younger patients and 33.6 months in the older patients.
There was no significant difference in percentage weight loss between younger and older patients, at 6.9% and 7.3%, respectively, and no difference in percentage reduction in BMI, at 8.1% versus 7.8%.
Further analysis demonstrated that there was no significant correlation between age at referral to the hospital-based service and percentage weight loss (correlation coefficient, –0.13).
Dr. Halford said it would have been “useful” to know the proportion of patients achieving 5% and 10% weight loss because, if a third of patients lost more than 10% of their weight, “even in an elderly population, that would suggest there’d be real benefits in terms of things like type 2 diabetes,” he noted.
And he would like to have seen more data around how long participants had been struggling with obesity, as it’s “just an assumption that the second group is further down the path because they’re older, but we can’t be 100% sure.”
The team noted the study is limited by being retrospective and including a random selection of patients attending the service rather than the entire cohort.
Dr. Halford agreed but said the analysis is a “starting point” and could be used as a platform to conduct “much more systematic research on this area.”
No funding or relevant financial relationships were declared.
A version of this article originally appeared on Medscape.com.
Older adults should be recommended for hospital-based lifestyle interventions to reduce weight, say U.K. investigators after finding there was no difference in weight loss between older and younger individuals in their program for those with morbid obesity.
Thomas M. Barber, PhD, and colleagues looked back at nearly 250 randomly selected adults who attended their obesity service over an 11-year period.
Older individuals, defined as aged 60 years and over, had higher rates of type 2 diabetes but experienced a similar percentage weight loss and reduction in body mass index (BMI) as younger patients over the course of around 40 months.
“Age should be no barrier to lifestyle management of obesity,” said Dr. Barber, of University Hospitals Coventry (England) and Warwickshire, in a news release from his institution. “Rather than putting up barriers to older people accessing weight-loss programs, we should be proactively facilitating that process. To do otherwise would risk further and unnecessary neglect of older people through societal ageist misconceptions.”
He urged service providers and policy makers to “appreciate the importance of weight loss in older people with obesity for the maintenance of health and well-being and the facilitation of healthy aging. Furthermore, age per se should not contribute toward clinical decisions regarding the implementation of lifestyle management of older people.”
The research was published online Nov. 22 in Clinical Endocrinology.
Real-world data will inform clinical practice
Jason Halford, PhD, a professor of biological psychology and health behavior, said in an interview: “The fear is that older patients are perceived not to respond” to lifestyle interventions to control obesity, “and that’s clearly a fallacy, according to this study.”
The findings are strengthened by the fact that these are real-world data, “and so it will inform clinical practice,” he added.
And one of the “more interesting” findings was that [type 2] diabetes was “more prevalent” in the older group “but they’re still losing weight,” he noted.
“Traditionally it’s been thought that people with type 2 diabetes find it more difficult to lose weight because you’re trying to manage two conditions,” said Dr. Halford, of the University of Leeds (England), who is also president-elect of the European Association for the Study of Obesity.
Don’t discount older patients
The researchers note that many of the comorbidities associated with obesity “develop over time” and that “no one is immune to obesity,” regardless of their age, sex, ethnicity, and socioeconomic status.
Barber said there are “a number of reasons” why health care professionals “may discount weight loss in older people,” including “an ‘ageist’ perspective that weight-loss is not relevant to older people and misconceptions of reduced ability of older people to lose weight through dietary modification and increased exercise.”
And “older people may feel that hospital-based obesity services are not for them,” he noted.
To determine the effect of age on the ability to lose weight through lifestyle interventions, Dr. Barber and colleagues randomly selected 242 patients with morbid obesity who attended their hospital-based service between 2005 and 2016.
Of these, 167 were aged 18-60 years and 75 were aged 60 years and older. Most participants were women (75.4% of the younger patients and 60.0% of the older patients).
The proportion of patients with confirmed diabetes was markedly higher in the older group, compared with the younger group, at 62.7% versus 35.3%, although older patients had a significantly lower baseline BMI, at 46.9 versus 49.7 kg/m2 (P < .05).
The average duration of the lifestyle intervention was over 3 years (41.5 months) in the younger patients and 33.6 months in the older patients.
There was no significant difference in percentage weight loss between younger and older patients, at 6.9% and 7.3%, respectively, and no difference in percentage reduction in BMI, at 8.1% versus 7.8%.
Further analysis demonstrated that there was no significant correlation between age at referral to the hospital-based service and percentage weight loss (correlation coefficient, –0.13).
Dr. Halford said it would have been “useful” to know the proportion of patients achieving 5% and 10% weight loss because, if a third of patients lost more than 10% of their weight, “even in an elderly population, that would suggest there’d be real benefits in terms of things like type 2 diabetes,” he noted.
And he would like to have seen more data around how long participants had been struggling with obesity, as it’s “just an assumption that the second group is further down the path because they’re older, but we can’t be 100% sure.”
The team noted the study is limited by being retrospective and including a random selection of patients attending the service rather than the entire cohort.
Dr. Halford agreed but said the analysis is a “starting point” and could be used as a platform to conduct “much more systematic research on this area.”
No funding or relevant financial relationships were declared.
A version of this article originally appeared on Medscape.com.
Obesity phenotyping matches patients with more effective interventions
A phenotype-guided strategy for systematically matching weight-loss patients to their potentially ideal weight-loss drug roughly doubled treatment efficacy, compared with usual practice, in a single-center, randomized study with 268 patients.
In contrast, in 200 patients who received weight loss–drug therapy selected by routine means, 35% achieved greater than 10% loss compared with their starting weight, Andres J. Acosta, MD, said at the virtual ObesityWeek® Interactive 2020 meeting.
The phenotype-guided strategy also led to an average 16% weight loss from baseline after 12 months, compared with a 9% average loss among the usual-care controls, reported Dr. Acosta, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
A “one-size-fits-all approach to weight loss treatment is not working,” he declared. “Our long-term goal is to develop a personalized approach to obesity management.”
Personalized weight loss treatment isn’t new
“The better we can match treatment to a patient’s needs, the more likely it will succeed. That’s not a brand new idea. They are trying to standardize the way that we classify the disorders that play a role in why a person gains weight or has trouble losing weight,” commented John D. Clark III, MD, an internal medicine physician and weight-management specialist at UT Southwestern Medical Center in Dallas.
The increased weight loss levels that Dr. Acosta reported in patients who underwent the study’s phenotyping protocol and received tailored treatment “are similar to the numbers we see when a patient’s treatment is the right fit for them. You see weight loss in these ranges,” Dr. Clark said in an interview.
The study run by Dr. Acosta and his associates consisted of two phases. First, they established normal and abnormal ranges for four different obesity phenotypes by studying 100 patients with obesity. The patients underwent an extensive and uniform workup designed to classify their obesity phenotype.
Four obesity phenotypes
The researchers categorized patients into one of four types:
- Disordered initial eating satiation, called ‘hungry brain,” and assessed by measuring food intake at a buffet, ad libidum meal.
- Disordered maintenance of satiety, called “hungry gut,” assessed by both a gastric-emptying study as well as patient self-assessment for postprandial fullness.
- “Emotional hunger,” assessed with two questionnaires.
- Disordered energy expenditure, called “slow burn,” assessed by measuring basal metabolic rate, and self-reports of both exercise and nonexercise activity.
Dr. Acosta estimated that the complete workup to assess all four potential phenotypes costs about $1,200.
The researchers then applied the 75th percentile value from each of these assessments to 450 patients with obesity in their clinic to see the prevalence of the four phenotypes. They identified a single phenotype in 58% of these patients, including 18% with hungry gut, 16% with hungry brain, 12% with emotional hunger, and 12% with slow burn. An additional 27% of the patients were positive for two or more phenotypes (including 9% who were positive for all four phenotypes), and 15% did not test positive for any of the four phenotypes.
Phenotype-guided treatments
They then applied their findings in a prospective randomized study that matched a drug intervention to each of the four phenotypes during a year-long, comprehensive weight-loss program at the Mayo Clinic’s Weight Management Clinic. The study randomized 100 patients to the phenotype-driven arm, with 68 of these patients receiving their assigned drug, and 200 patients served as controls. Patients averaged about 47 years old, and their average body mass index was about 41 kg/m2.
The investigational arm included 30 patients classified as having a hungry brain, with 20 of these patients treated with phentermine plus topiramate and 10 treated with lorcaserin (before it was withdrawn by the Food and Drug Administration); 12 with hungry gut and treated with liraglutide (Saxenda); 19 with emotional hunger who received naltrexone SR/bupropion SR (Contrave); and seven with slow burn who received phentermine.
The control arm included 200 patients seeking weight loss treatment at Mayo who did not undergo phenotyping and received their drug treatment based on their personal preference in consultation with their Mayo physician. In this group, drug treatment broke down as 106 patients (53%) on phentermine plus topiramate, 41 (21%) on liraglutide, 34 (17%) on phentermine alone, 14 (7%) on naltrexone SR/bupropion SR, and 5 patients (3%) on locaserin (percentages total 101% because of rounding).
Overall, phenotyping led to more patients treated with naltrexone SR/buproprion SR and lorcaserin and fewer treated with phentermine or phentermine and topiramate ER. All patients were eligible to also receive behavioral interventions as needed.
“We do a lot of testing to identify the phenotype,” in addition to gathering additional clues from a detailed history, said Dr. Acosta. Patients identified with more than one phenotype in routine practice at Mayo are often begun on more than one drug. When phenotyping fails to classify a patient, Dr. Acosta puts the patient on a low-calorie diet and then does a follow-up assessment “to see if the phenotype pops up as a metabolic adaptation.”
“This is something we’re all working toward” in the obesity management field. “How can we better identify the underlying causes in a way that can fit into the work flow. How can we move from research to things we can use daily in the clinic,” observed Dr. Clark. “We need a lot more investigation to determine how well this works in the real world. Are there other tools we can use that are not as expensive” as what Dr. Acosta used for this study?
“For this proof of concept study, it made sense to be very rigorous, but that probably is not realistic for every patient. What are other ways to get this information, or perhaps only use an extensive workup when initial weight loss attempts are unsuccessful,” Dr. Clark suggested.
A phenotype-guided strategy for systematically matching weight-loss patients to their potentially ideal weight-loss drug roughly doubled treatment efficacy, compared with usual practice, in a single-center, randomized study with 268 patients.
In contrast, in 200 patients who received weight loss–drug therapy selected by routine means, 35% achieved greater than 10% loss compared with their starting weight, Andres J. Acosta, MD, said at the virtual ObesityWeek® Interactive 2020 meeting.
The phenotype-guided strategy also led to an average 16% weight loss from baseline after 12 months, compared with a 9% average loss among the usual-care controls, reported Dr. Acosta, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
A “one-size-fits-all approach to weight loss treatment is not working,” he declared. “Our long-term goal is to develop a personalized approach to obesity management.”
Personalized weight loss treatment isn’t new
“The better we can match treatment to a patient’s needs, the more likely it will succeed. That’s not a brand new idea. They are trying to standardize the way that we classify the disorders that play a role in why a person gains weight or has trouble losing weight,” commented John D. Clark III, MD, an internal medicine physician and weight-management specialist at UT Southwestern Medical Center in Dallas.
The increased weight loss levels that Dr. Acosta reported in patients who underwent the study’s phenotyping protocol and received tailored treatment “are similar to the numbers we see when a patient’s treatment is the right fit for them. You see weight loss in these ranges,” Dr. Clark said in an interview.
The study run by Dr. Acosta and his associates consisted of two phases. First, they established normal and abnormal ranges for four different obesity phenotypes by studying 100 patients with obesity. The patients underwent an extensive and uniform workup designed to classify their obesity phenotype.
Four obesity phenotypes
The researchers categorized patients into one of four types:
- Disordered initial eating satiation, called ‘hungry brain,” and assessed by measuring food intake at a buffet, ad libidum meal.
- Disordered maintenance of satiety, called “hungry gut,” assessed by both a gastric-emptying study as well as patient self-assessment for postprandial fullness.
- “Emotional hunger,” assessed with two questionnaires.
- Disordered energy expenditure, called “slow burn,” assessed by measuring basal metabolic rate, and self-reports of both exercise and nonexercise activity.
Dr. Acosta estimated that the complete workup to assess all four potential phenotypes costs about $1,200.
The researchers then applied the 75th percentile value from each of these assessments to 450 patients with obesity in their clinic to see the prevalence of the four phenotypes. They identified a single phenotype in 58% of these patients, including 18% with hungry gut, 16% with hungry brain, 12% with emotional hunger, and 12% with slow burn. An additional 27% of the patients were positive for two or more phenotypes (including 9% who were positive for all four phenotypes), and 15% did not test positive for any of the four phenotypes.
Phenotype-guided treatments
They then applied their findings in a prospective randomized study that matched a drug intervention to each of the four phenotypes during a year-long, comprehensive weight-loss program at the Mayo Clinic’s Weight Management Clinic. The study randomized 100 patients to the phenotype-driven arm, with 68 of these patients receiving their assigned drug, and 200 patients served as controls. Patients averaged about 47 years old, and their average body mass index was about 41 kg/m2.
The investigational arm included 30 patients classified as having a hungry brain, with 20 of these patients treated with phentermine plus topiramate and 10 treated with lorcaserin (before it was withdrawn by the Food and Drug Administration); 12 with hungry gut and treated with liraglutide (Saxenda); 19 with emotional hunger who received naltrexone SR/bupropion SR (Contrave); and seven with slow burn who received phentermine.
The control arm included 200 patients seeking weight loss treatment at Mayo who did not undergo phenotyping and received their drug treatment based on their personal preference in consultation with their Mayo physician. In this group, drug treatment broke down as 106 patients (53%) on phentermine plus topiramate, 41 (21%) on liraglutide, 34 (17%) on phentermine alone, 14 (7%) on naltrexone SR/bupropion SR, and 5 patients (3%) on locaserin (percentages total 101% because of rounding).
Overall, phenotyping led to more patients treated with naltrexone SR/buproprion SR and lorcaserin and fewer treated with phentermine or phentermine and topiramate ER. All patients were eligible to also receive behavioral interventions as needed.
“We do a lot of testing to identify the phenotype,” in addition to gathering additional clues from a detailed history, said Dr. Acosta. Patients identified with more than one phenotype in routine practice at Mayo are often begun on more than one drug. When phenotyping fails to classify a patient, Dr. Acosta puts the patient on a low-calorie diet and then does a follow-up assessment “to see if the phenotype pops up as a metabolic adaptation.”
“This is something we’re all working toward” in the obesity management field. “How can we better identify the underlying causes in a way that can fit into the work flow. How can we move from research to things we can use daily in the clinic,” observed Dr. Clark. “We need a lot more investigation to determine how well this works in the real world. Are there other tools we can use that are not as expensive” as what Dr. Acosta used for this study?
“For this proof of concept study, it made sense to be very rigorous, but that probably is not realistic for every patient. What are other ways to get this information, or perhaps only use an extensive workup when initial weight loss attempts are unsuccessful,” Dr. Clark suggested.
A phenotype-guided strategy for systematically matching weight-loss patients to their potentially ideal weight-loss drug roughly doubled treatment efficacy, compared with usual practice, in a single-center, randomized study with 268 patients.
In contrast, in 200 patients who received weight loss–drug therapy selected by routine means, 35% achieved greater than 10% loss compared with their starting weight, Andres J. Acosta, MD, said at the virtual ObesityWeek® Interactive 2020 meeting.
The phenotype-guided strategy also led to an average 16% weight loss from baseline after 12 months, compared with a 9% average loss among the usual-care controls, reported Dr. Acosta, a gastroenterologist at the Mayo Clinic in Rochester, Minn.
A “one-size-fits-all approach to weight loss treatment is not working,” he declared. “Our long-term goal is to develop a personalized approach to obesity management.”
Personalized weight loss treatment isn’t new
“The better we can match treatment to a patient’s needs, the more likely it will succeed. That’s not a brand new idea. They are trying to standardize the way that we classify the disorders that play a role in why a person gains weight or has trouble losing weight,” commented John D. Clark III, MD, an internal medicine physician and weight-management specialist at UT Southwestern Medical Center in Dallas.
The increased weight loss levels that Dr. Acosta reported in patients who underwent the study’s phenotyping protocol and received tailored treatment “are similar to the numbers we see when a patient’s treatment is the right fit for them. You see weight loss in these ranges,” Dr. Clark said in an interview.
The study run by Dr. Acosta and his associates consisted of two phases. First, they established normal and abnormal ranges for four different obesity phenotypes by studying 100 patients with obesity. The patients underwent an extensive and uniform workup designed to classify their obesity phenotype.
Four obesity phenotypes
The researchers categorized patients into one of four types:
- Disordered initial eating satiation, called ‘hungry brain,” and assessed by measuring food intake at a buffet, ad libidum meal.
- Disordered maintenance of satiety, called “hungry gut,” assessed by both a gastric-emptying study as well as patient self-assessment for postprandial fullness.
- “Emotional hunger,” assessed with two questionnaires.
- Disordered energy expenditure, called “slow burn,” assessed by measuring basal metabolic rate, and self-reports of both exercise and nonexercise activity.
Dr. Acosta estimated that the complete workup to assess all four potential phenotypes costs about $1,200.
The researchers then applied the 75th percentile value from each of these assessments to 450 patients with obesity in their clinic to see the prevalence of the four phenotypes. They identified a single phenotype in 58% of these patients, including 18% with hungry gut, 16% with hungry brain, 12% with emotional hunger, and 12% with slow burn. An additional 27% of the patients were positive for two or more phenotypes (including 9% who were positive for all four phenotypes), and 15% did not test positive for any of the four phenotypes.
Phenotype-guided treatments
They then applied their findings in a prospective randomized study that matched a drug intervention to each of the four phenotypes during a year-long, comprehensive weight-loss program at the Mayo Clinic’s Weight Management Clinic. The study randomized 100 patients to the phenotype-driven arm, with 68 of these patients receiving their assigned drug, and 200 patients served as controls. Patients averaged about 47 years old, and their average body mass index was about 41 kg/m2.
The investigational arm included 30 patients classified as having a hungry brain, with 20 of these patients treated with phentermine plus topiramate and 10 treated with lorcaserin (before it was withdrawn by the Food and Drug Administration); 12 with hungry gut and treated with liraglutide (Saxenda); 19 with emotional hunger who received naltrexone SR/bupropion SR (Contrave); and seven with slow burn who received phentermine.
The control arm included 200 patients seeking weight loss treatment at Mayo who did not undergo phenotyping and received their drug treatment based on their personal preference in consultation with their Mayo physician. In this group, drug treatment broke down as 106 patients (53%) on phentermine plus topiramate, 41 (21%) on liraglutide, 34 (17%) on phentermine alone, 14 (7%) on naltrexone SR/bupropion SR, and 5 patients (3%) on locaserin (percentages total 101% because of rounding).
Overall, phenotyping led to more patients treated with naltrexone SR/buproprion SR and lorcaserin and fewer treated with phentermine or phentermine and topiramate ER. All patients were eligible to also receive behavioral interventions as needed.
“We do a lot of testing to identify the phenotype,” in addition to gathering additional clues from a detailed history, said Dr. Acosta. Patients identified with more than one phenotype in routine practice at Mayo are often begun on more than one drug. When phenotyping fails to classify a patient, Dr. Acosta puts the patient on a low-calorie diet and then does a follow-up assessment “to see if the phenotype pops up as a metabolic adaptation.”
“This is something we’re all working toward” in the obesity management field. “How can we better identify the underlying causes in a way that can fit into the work flow. How can we move from research to things we can use daily in the clinic,” observed Dr. Clark. “We need a lot more investigation to determine how well this works in the real world. Are there other tools we can use that are not as expensive” as what Dr. Acosta used for this study?
“For this proof of concept study, it made sense to be very rigorous, but that probably is not realistic for every patient. What are other ways to get this information, or perhaps only use an extensive workup when initial weight loss attempts are unsuccessful,” Dr. Clark suggested.
FROM OBESITY WEEK 2020
New AHA scientific statement on menopause and CVD risk
Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.
“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.
“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.
The statement was published online Nov. 30 in Circulation.
Evolution in knowledge
During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.
“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.
“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.
The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.
Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.
Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.
Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.
Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
Lifestyle interventions
The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.
Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.
Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.
“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.
There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.
The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.
They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.
The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.
“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.
“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.
The statement was published online Nov. 30 in Circulation.
Evolution in knowledge
During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.
“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.
“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.
The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.
Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.
Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.
Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.
Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
Lifestyle interventions
The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.
Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.
Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.
“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.
There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.
The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.
They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.
The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.
“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.
“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.
The statement was published online Nov. 30 in Circulation.
Evolution in knowledge
During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.
“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.
“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.
The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.
Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.
Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.
Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.
Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
Lifestyle interventions
The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.
Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.
Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.
“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.
There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.
The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.
They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.
The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
New study pinpoints how Mediterranean diet reduces diabetes risk
The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.
While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.
However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m2), according to the findings.
“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.
“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.
“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.
“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m2
The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.
The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.
To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.
Over the course of the study, 2,307 participants developed type 2 diabetes.
With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).
The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).
Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).
Differences in hemoglobin A1c levels had a limited effect on the risk (2%).
Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m2).
Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.
“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.
“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m2, but the risk goes up exponentially at around a BMI of 25 and higher.”
Strong role of insulin resistance a surprise
The strong role of insulin resistance was a surprise, Dr. Mora added.
“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.
“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”
Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.
“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.
A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.
In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.
However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.
“And of course, the more the adherence, the more the benefit.”
The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).
A version of this article originally appeared on Medscape.com.
The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.
While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.
However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m2), according to the findings.
“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.
“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.
“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.
“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m2
The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.
The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.
To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.
Over the course of the study, 2,307 participants developed type 2 diabetes.
With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).
The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).
Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).
Differences in hemoglobin A1c levels had a limited effect on the risk (2%).
Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m2).
Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.
“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.
“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m2, but the risk goes up exponentially at around a BMI of 25 and higher.”
Strong role of insulin resistance a surprise
The strong role of insulin resistance was a surprise, Dr. Mora added.
“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.
“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”
Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.
“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.
A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.
In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.
However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.
“And of course, the more the adherence, the more the benefit.”
The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).
A version of this article originally appeared on Medscape.com.
The known reduction in the risk of type 2 diabetes associated with adoption of the Mediterranean diet appears specifically attributed to its beneficial effects on some key factors, a new study published online in JAMA Network Open reveals.
While a reduction in body mass index may be somewhat obvious, other mechanisms include beneficial effects on insulin resistance, lipoprotein metabolism, and inflammation.
However, the diet’s antidiabetes effect does not appear to extend to people whose weight is considered healthy (BMI under 25 kg/m2), according to the findings.
“It is striking to see in these U.S. women how strong the long-term antidiabetic properties of a Mediterranean-type dietary pattern are,” senior author Samia Mora, MD, of the Center for Lipid Metabolomics, Brigham and Women’s Hospital, Harvard Medical School, Boston, said in an interview.
“While it was known that the Mediterranean diet has many health benefits in particular on metabolism and inflammation, it was not previously known which of these biological pathways may be contributing to the lower risk of diabetes and to what magnitude.
“Our findings support the idea that by improving their diet, people can improve their future risk of type 2 diabetes, particularly if they are overweight or have obesity,” she added.
“And it’s important to note that many of these changes don’t happen right away. While metabolism can change over a short period of time, our study indicates that there are longer term changes happening that may provide protection over decades.”
Mediterranean diet reduced diabetes risk in those with BMI ≥ 25 kg/m2
The Mediterranean diet, with an emphasis on healthy olive oil as the predominant source of oil, favors fruits, vegetables, legumes, nuts, seeds, fish, and dairy products, while limiting intake of red and processed meats as well as sweets.
The diet has been linked to as much as a 25%-30% reduction in the risk of diabetes in previous observational studies.
To investigate the precise mechanisms that underlie the prevention of diabetes, lead author Shafqat Ahmad, PhD, also of Harvard, and colleagues examined data from 25,317 healthy women participating in the Women’s Health Study who had baseline assessments between September 1992 and May 1995. They were a mean age of 52.9 years at baseline.
Over the course of the study, 2,307 participants developed type 2 diabetes.
With a mean follow-up of 19.8 years, those who had the highest self-reported adherence to the Mediterranean diet (a score ≥ 6 on a scale of 0-6) at baseline, had as much as a 30% lower risk of developing type 2 diabetes after multivariate adjustments, compared to those with a lower Mediterranean diet score (a score ≤ 3; hazard ratio, 0.70).
The diabetes-related biomarkers that contributed the most to the reduced risk were insulin resistance, accounting for 65% of the reduction, followed by BMI (55.5%), high-density lipoprotein measures (53%), and inflammation (52.5%).
Other factors, though to a lesser degree, included branched-chain amino acids (34.5%), very low-density lipoprotein measures (32.0%), low-density lipoprotein measures (31.0%), blood pressure (29.0%), and apolipoproteins (23.5%).
Differences in hemoglobin A1c levels had a limited effect on the risk (2%).
Notably, a subgroup analysis looking at effects of the diet according to baseline BMI showed the reductions in type 2 diabetes associated with higher intake of the Mediterranean diet extended only to those with an above normal weight (BMI ≥ 25 kg/m2).
Dr. Mora noted that, as this was not a prespecified analysis, these findings should be viewed as hypothesis-generating, but are consistent with the well-known increase in diabetes risk seen with a higher BMI.
“[The finding] fits with the biology and pathogenesis of type 2 diabetes that is driven in large part by excess weight, in particular for visceral adiposity and its resulting metabolic dysregulation and inflammation,” she said.
“We know from other studies, such as the Nurses’ Health Study, that the risk for type 2 diabetes in women increases even at BMI levels below 25 kg/m2, but the risk goes up exponentially at around a BMI of 25 and higher.”
Strong role of insulin resistance a surprise
The strong role of insulin resistance was a surprise, Dr. Mora added.
“We were surprised that insulin resistance, measured by a simple blood biomarker, would have the strongest mediating effect – even stronger than BMI – for the Mediterranean diet on risk of diabetes,” she noted.
“This could represent an opportunity to intervene earlier and more intensively on improving insulin resistance through dietary approaches such as the Mediterranean diet, especially [because] insulin resistance can precede by years and decades the overt hyperglycemia and clinical diagnosis of diabetes.”
Yet another surprise was that A1c had no substantial mediating effect on the reduction of diabetes risk with the Mediterranean diet.
“This could suggest that the cat is out of the bag by the time the A1c rises,” Dr. Mora observed.
A study limitation is that the Women’s Health Study consisted of well-educated U.S. women who were health professionals and predominantly White, so the results may not be generalizable to men or individuals of other races or ethnicities.
In addition, BMI was self-reported and participants were not uniformly screened for diabetes, therefore surveillance bias could be possible.
However, the findings suggest that “even a small increase in adherence to the Mediterranean diet has substantial benefits over many years in preventing diabetes, among many other health benefits such as lowering insulin resistance and inflammation, improving lipid metabolism, and lowering blood pressure,” Mora said.
“And of course, the more the adherence, the more the benefit.”
The study received support through grants from the National Institutes of Health, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the American Heart Association, and the Molino Family Trust. A coauthor is listed as a coinventor on patents held by Brigham and Women’s Hospital related to the use of inflammatory biomarkers in cardiovascular disease (licensed to AstraZeneca and Siemens).
A version of this article originally appeared on Medscape.com.
Statins beneficial in elderly, guidelines should be strengthened
Contrary to historical evidence, two new studies show.
“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.
“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.
“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).
The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.
“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.
“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
No RCTs have included patients older than 70
For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.
However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.
Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.
As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
Primary prevention: CV events increase with elevated LDL cholesterol in older age
Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.
Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.
Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.
In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).
Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.
Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).
The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.
“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.
With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.
With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.
“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”
“These robust findings are novel,” he and his colleagues stressed.
Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.
The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
Unequivocal reductions in events in elderly, comparable with younger patients
In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.
The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.
The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.
The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).
Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).
“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.
“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.
“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”
The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”
The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.
A version of this article originally appeared on Medscape.com.
Contrary to historical evidence, two new studies show.
“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.
“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.
“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).
The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.
“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.
“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
No RCTs have included patients older than 70
For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.
However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.
Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.
As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
Primary prevention: CV events increase with elevated LDL cholesterol in older age
Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.
Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.
Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.
In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).
Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.
Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).
The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.
“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.
With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.
With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.
“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”
“These robust findings are novel,” he and his colleagues stressed.
Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.
The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
Unequivocal reductions in events in elderly, comparable with younger patients
In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.
The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.
The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.
The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).
Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).
“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.
“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.
“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”
The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”
The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.
A version of this article originally appeared on Medscape.com.
Contrary to historical evidence, two new studies show.
“By contrast with previous historical studies, our data show that LDL cholesterol is an important risk factor for myocardial infarction and atherosclerotic cardiovascular disease in a contemporary primary prevention cohort of individuals aged 70 to 100 years,” Borge Nordestgaard, MD, of the University of Copenhagen, and colleagues noted in the first of the two studies, published this week in the Lancet.
“By lowering LDL cholesterol in healthy individuals aged 70-100 years, the potential for preventing myocardial infarctions and atherosclerotic cardiovascular disease is huge, and at a substantially lower number needed to treat when compared with those aged 20-69 years,” they added.
“These findings support the concept of the cumulative burden of LDL cholesterol over one’s lifetime and the progressive increase in risk for atherosclerotic cardiovascular disease, including myocardial infarction, with age,” added Frederick J. Raal, PhD, and Farzahna Mohamed, MB BCh, of the University of the Witwatersrand, Johannesburg, South Africa, in an editorial published with both new studies in the Lancet (2020 Nov 10. doi: 10.1016/S0140-6736[20]32333-3).
The studies underscore the need for clinicians to consider continued risks associated with elevated LDL cholesterol in older age, they stressed, adding that statins are also beneficial for younger persons at risk to prevent conditions from worsening.
“The average age of patients in all the trials analyzed was older than 60 years, an age when atherosclerotic cardiovascular disease is already well established,” the editorialists wrote.
“Lipid-lowering therapy should be initiated at a younger age, preferably before age 40 years, in those at risk to delay the onset of atherosclerosis, rather than try to manage the condition once fully established or advanced,” they stressed.
No RCTs have included patients older than 70
For persons aged 40-75 years, elevated LDL cholesterol levels are a known risk factor for MI and atherosclerotic cardiovascular disease, and there is consensus in guidelines regarding treatment with statins.
However, the risk for people older than 70 is controversial. Some studies show little or no association between elevated LDL cholesterol levels and an increased risk for MI.
Contributing to the uncertainty is that few of the randomized, controlled trials that have investigated the question have included patients aged older than 70 years.
As a consequence, many practice guidelines have noted that the level of evidence in older patients is low, and some organizations have lowered the strength of recommendations regarding the treatment for older patients in comparison with younger patients.
Primary prevention: CV events increase with elevated LDL cholesterol in older age
Dr. Nordestgaard and colleagues studied data on 91,131 people living in Copenhagen who did not have atherosclerotic cardiovascular disease or diabetes at baseline and were not taking statins.
Of the participants, 10,592 were aged 70-79 years, and 3,188 participants were aged 80-100 years.
Over an average follow-up period of 7.7 years, 1,515 participants had a first MI, and 3,389 developed atherosclerotic cardiovascular disease.
In the primary-prevention cohort, after multivariate adjustment, the risk of having a heart attack per 1.0 mmol/L increase in LDL cholesterol was increased in the group overall (hazard ratio, 1.34). The increased risk was observed for all age groups, including those aged 80-100 years (HR, 1.28), 70-79 (HR, 1.25), 60-69 (HR, 1.29), 50-59 (HR, 1.28), and 20-49 (HR, 1.68).
Risk for atherosclerotic cardiovascular disease was also raised per 1.0 mmol/L increase in LDL cholesterol overall (HR, 1.16) and in all age groups, particularly those aged 70-100 years.
Greater elevations in LDL cholesterol (5.0 mmol/L or higher, indicative of possible familial hypercholesterolemia) were associated with a notably higher risk for heart attack after multivariate adjustment in people aged 80-100 (HR, 2.99). Risk was also higher among those aged 70-79 (HR, 1.82).
The highest incidence was in those older than 70. The rate was 8.5 heart attacks per 1,000 people per year among those aged 80-100 and 5.2 heart attacks per 1,000 in those aged 70-79. The rates were 2.5 per 1,000 among those 60-69, 1.8 for those aged 50-59, and 0.8 for those aged 20-49.
“The absolute risk [of cardiovascular events] is of course much higher in the elderly than those under the age of 75, but what was a surprise was how clear our results were on a relative risk scale, that the risk associated with elevated LDL [cholesterol] was as high in people aged 80-100 as the younger patients,” Dr. Nordestgaard said in an interview.
With regard to the benefits of cholesterol-lowering drugs, the study showed that the number needed to prevent one heart attack over 5 years was 80 among those aged 80-100; the number was 439 for people aged 50-59.
With regard to stronger statins, when moderate-intensity statins were used, the number needed to treat to prevent one cardiovascular disease event of any type dropped to 42 for patients aged 80-100. It was 88 for those aged 70-79, 164 for those aged 60-69, 345 for those aged 50-59, and 769 for those aged 20-49.
“The clinical significance of this is that it appears those in older age groups indeed benefit from cholesterol-lowering therapy,” Dr. Nordestgaard said. “I think many people have this idea that LDL [cholesterol] is not important over the age of about 70-75, but that’s not the case.”
“These robust findings are novel,” he and his colleagues stressed.
Despite these observational findings, the South African editorialists noted that “whether lipid-lowering therapy should be initiated for primary prevention in people aged 75 years or older is unclear,” owing to the host of risks and benefits that need to be balanced.
The findings of an ongoing randomized, placebo-controlled trial (STAREE) may answer this question, they wrote. It is investigating primary prevention in 18,000 older patients (≥70 years) who are being randomly assigned to receive atorvastatin 40 mg/d or placebo. The study is seeking to determine whether statin treatment extends the length of a disability-free life, which will be assessed on the basis of survival outside permanent residential care. Results are expected in 2022-2023.
Unequivocal reductions in events in elderly, comparable with younger patients
In the second study (Lancet. 2020 Nov 10. doi: 10.1016/S0140-6736[20]32332-1), Baris Gencer, MD, of Brigham and Women’s Hospital, Boston, =and colleagues evaluated the effects of statins and other cholesterol-lowering drugs, including ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, in older versus younger patients.
The systematic review and meta-analysis of 29 randomized controlled trials, also published in the Lancet, were presented virtually as a poster as part of the 2020 American Heart Association scientific session. It included data on 244,090 patients, including 21,492 aged 75 years and older.
The meta-analysis included studies of cardiovascular outcomes of a guideline-recommended LDL cholesterol–lowering drug, with a median follow-up of at least 2 years and inclusion of data on patients aged 75 years and older.
The results showed that over a median follow-up of 2.2 to 6 years, statin use by older patients was associated with a relative risk reduction of major vascular events of 26% per 1 mmol/L reduction in LDL cholesterol (P = .0019), which was comparable with a risk reduction of 15% per 1 mmol/L reduction in LDL cholesterol for patients younger than 75 years (P = .37, compared with older patients).
Treatment of older patients with LDL cholesterol–lowering drugs was also associated with significantly improved outcomes in cardiovascular death (risk ratio, 0.85), MI (RR, 0.80), stroke (RR, 0.73), and coronary revascularization (RR, 0.80).
“We found an unequivocal reduction in the risk of major vascular events with both statin and nonstatin LDL cholesterol-lowering treatments, which was similar to that seen in younger patients,” the authors wrote.
“Cholesterol-lowering medications are affordable drugs that have reduced risk of heart disease for millions of people worldwide, but until now, their benefits for older people have remained less certain,” said lead author Marc Sabatine, MD, also of Brigham and Women’s Hospital, in a Lancet press release.
“Our analysis indicates that these therapies are as effective in reducing cardiovascular events and deaths in people aged 75 years and over as they are in younger people. We found no offsetting safety concerns, and together, these results should strengthen guideline recommendations for the use of cholesterol-lowering medications, including statin and nonstatin therapy, in elderly people.”
The editorialists agreed: “More than 80% of fatal cardiovascular events occur in individuals older than 65 years, and the incidence of cardiovascular events is increasing in those older than 80 years; therefore, the findings of Gencer and colleagues’ study should encourage the use of lipid-lowering therapy in older patients.”
The authors of the two studies have disclosed no relevant financial relationships. Dr. Raal has received research grants, honoraria, or consulting fees for advisory board membership, professional input, and lectures on lipid-lowering drug therapy from Amgen, Regeneron, Sanofi, Novartis, and the Medicines Company.
A version of this article originally appeared on Medscape.com.