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Physical activity paradoxically tied to higher coronary calcium
new observational data suggest.
In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.
“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.
This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.
“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.
The study is published online September 20 in Heart.
The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.
In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.
“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.
The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.
At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.
Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).
On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.
Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.
Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.
A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.
At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).
Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.
A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.
The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.
Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.
“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.
“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.
“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.
Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”
“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.
The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.
“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.
Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.
A version of this article first appeared on Medscape.com.
new observational data suggest.
In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.
“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.
This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.
“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.
The study is published online September 20 in Heart.
The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.
In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.
“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.
The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.
At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.
Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).
On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.
Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.
Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.
A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.
At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).
Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.
A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.
The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.
Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.
“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.
“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.
“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.
Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”
“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.
The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.
“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.
Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.
A version of this article first appeared on Medscape.com.
new observational data suggest.
In a prospective cohort study of Korean men and women 18 years and older, participants who were the most physically active had the fastest progression of their coronary artery calcium (CAC) scores at 5 years, compared with those who were the least physically active.
“People who exercise may have an increase in their coronary calcium levels, but this is not necessarily bad news. This may mean that atherosclerotic lesions in the coronary arteries are becoming more stable and less dangerous, but we need additional research to understand these changes,” Eliseo Guallar, MD, PhD, professor, Johns Hopkins Bloomberg School of Public Health, Baltimore, the study’s corresponding author, said in an interview.
This paradoxical effect notwithstanding, doctors should continue to advise their patients to follow the physical activity guidelines for Americans that were published in 2018, Dr. Guallar said.
“Physical activity is a key component of a healthy lifestyle. Our analysis can be useful, however, if someone starts exercising and sees that his or her coronary calcium score goes up,” he said.
The study is published online September 20 in Heart.
The degree of build-up of calcium deposits in the coronary arteries is used to determine future cardiovascular disease risk and to guide treatment to prevent myocardial infarction and stroke. A CAC score of at least 100 Agatston units indicates that treatment with statins is warranted, the researchers write.
In the current study, investigators — led by Ki-Chul Sung, MD, Sungkyunkwan University School of Medicine, Seoul, Korea, and Yun Soo Hong, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore — explored the link between different degrees of physical activity and the progression of CAC scores in healthy adults.
“While physical activity improves a wide array of cardiovascular and metabolic biomarkers, endurance athletes were more likely to have a coronary artery calcium (CAC) score >300 Agatston units or coronary plaques compared with sedentary men with a similar risk profile. It is not clear if exercise may itself be associated with calcification of the arteries,” the authors write.
The researchers studied 25,485 participants (22,741 men and 2,744 women) who were part of the Kangbuk Samsung Health Study. All were free of cardiovascular disease at study entry and underwent comprehensive health screening exams at one of two major health centers in Seoul and Suwon, South Korea, between March 1, 2011, and December 31, 2017.
At each exam, participants filled out a questionnaire that included questions on medical and family history, smoking habits, alcohol intake, and education level.
Participants were also quizzed at baseline about their physical activity, using the Korean version of the International Physical Activity Questionnaire Short Form (IPAQ-SF).
On the basis of that, they were categorized into one of three categories: inactive; moderately active, defined as at least 3 days of vigorous-intensity activity for at least 20 min/day or at least 5 days of moderate-intensity activity or walking for at least 30 min/ day or at least 5 days of any combination of walking and moderate- or vigorous-intensity activities, attaining at least 600 MET-min/week; or health-enhancing physically active (HEPA), defined as at least 3 days of vigorous-intensity activity, attaining at least 1,500 MET-min/week or 7 days of any combination of walking or moderate- or vigorous-intensity activities, attaining at least 3000 MET-min/week.
Of the study participants, 47% were classified as inactive, 38% as moderately active, and 15% as HEPA.
Those who were more physically active tended to be older and less likely to smoke than less physically active participants. They also had lower total cholesterol, more hypertension, and existing evidence of calcium deposits in their coronary arteries.
A graded association between physical activity level and the prevalence and progression of coronary artery calcification was seen, irrespective of CAC scores at the start of monitoring.
At baseline, the estimated adjusted average baseline CAC scores in inactive participants was 9.45 (95% CI, 8.76 - 10.14), in moderately active participants was 10.20 (95% CI, 9.40 - 11.00), and in HEPA participants was 12.04 (95% CI, 10.81 - 13.26).
Compared with the least active participants, the estimated adjusted 5-year average increases in CAC was 3.20 (95% CI, 0.72 - 5.69) in moderately active participants and 8.16 (95% CI, 4.80 - 11.53) in HEPA participants.
A higher level of physical activity was associated with faster progression of CAC scores, both in participants with CAC score of 0 at baseline and in those with prevalent CAC.
The authors note there are several limitations to consider when interpreting their findings. These include the absence of an objective assessment of physical activity, the inability to evaluate the association between physical activity and CAC levels with incident cardiovascular events because of a lack of data, and the lack of information on incident myocardial infarction, stroke, CAC density, or volume.
Physical activity might increase coronary atherosclerosis through mechanical stress and vessel wall injury of coronary arteries; physiologic responses during exercise, such as increased blood pressure; increased parathyroid hormone levels; and changes in coronary hemodynamics and inflammation. “In addition, other factors, such as diet, vitamins, and minerals, may change with physical activity,” the authors write.
“The second possibility is that physical activity may increase CAC scores without increasing cardiovascular disease risk,” they write.
“The cardiovascular benefits of physical activity are unquestionable,” the authors emphasize, adding that the national guidelines recommend at least 150 to 300 minutes per week of moderate-intensity or 75 to 150 minutes per week of vigorous-intensity aerobic physical activity.
“Patients and physicians, however, need to consider that engaging in physical activity may accelerate the progression of coronary calcium, possibly due to plaque healing, stabilization and calcification,” they conclude.
Dr. Guallar added: “We would like to link our research to clinical outcomes, so that we can really be sure that the increase in coronary calcium scores does not imply an increase in risk.”
“Do these findings mean that we should stop using coronary artery calcium scores to assess coronary artery disease?” ask Gaurav Gulsin, MD, and Alastair James Moss, MD, University of Leicester, United Kingdom, in an accompanying editorial.
The study highlights the complexity of interpreting CAC scores in patients who have implemented recommendations for physical activity or started statin therapy, they note.
“While proponents would argue that it is an effective tool to screen for subclinical atherosclerosis in asymptomatic individuals, clinicians should be cautious regarding the overuse of this test in otherwise healthy individuals. The coronary artery calcium paradox should not result in paradoxical care for our patients,” Dr. Gulsin and Dr. Moss conclude.
Dr. Sung, Dr. Hong, and the other study authors report no relevant financial relationships. The British Heart Foundation provides funding support for Dr. Gulsin and Dr. Moss.
A version of this article first appeared on Medscape.com.
Beta-blocker reduces lung inflammation in critical COVID-19
In a small study, intravenous administration of the beta-blocker metoprolol to critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) safely blunted lung inflammation associated with the disease.
Metoprolol administration also resulted in better oxygenation and fewer days on intensive mechanical ventilation and in the ICU, compared with no treatment.
These data suggest that metoprolol repurposing for the treatment of ARDS in COVID-19 patients is a safe and inexpensive strategy with the potential to improve outcomes, the researchers said.
“Metoprolol repurposing for the treatment of ARDS associated with COVID-19 is a safe and cheap intervention that can help to alleviate the massive personal and health care burden associated with the pandemic,” they concluded.
The results, from the MADRID-COVID pilot trial from Agustin Clemente-Moragon, BSc, Centro National de Investigaciones Cardiovasculares, Madrid, and colleagues, were published online Aug. 30, 2021, in the Journal of the American College of Cardiology.
In previous work, the researchers showed that metoprolol, but not other clinically available intravenous beta-blockers, abrogates neutrophil-driven exacerbated inflammation, neutrophil-platelet interaction, and formation of neutrophil extracellular traps in a mouse model of acute lung injury.
These results prompted the current pilot trial in 20 patients, ages 18-80 years, with COVID-19–associated ARDS.
Randomization was stratified by age (59 and younger vs. 60 and older), history of hypertension (yes or no), and circulating neutrophil counts (<6,000 vs. ≥6,000). Bronchoalveolar lavage (BAL) fluid and blood samples were obtained from patients at randomization and 24 hours after the third metoprolol dose in the treatment group, and on day 4 in controls.
Because of the cardiovascular effects of metoprolol, patients were monitored invasively and by echocardiography, the authors noted.
As expected, metoprolol significantly reduced heart rate (P < .01) and systolic blood pressure (P < .05), although both remained within the physiological range. Echocardiography showed no deterioration of cardiac function after metoprolol treatment.
To assess the ability of metoprolol to address neutrophil-mediated exacerbated lung inflammation, the researchers analyzed leukocyte populations in BAL samples by flow cytometry at baseline and on day 4.
At baseline, the metoprolol and control groups showed no differences in BAL neutrophil content. But on day 4, after 3 days of treatment with metoprolol, neutrophil content was significantly lower in the metoprolol group (median, 14.3 neutrophils/mcL) than in the control group (median, 397 neutrophils/mcL).
Metoprolol-treated patients also had lower total inflammatory-cell content and lower monocyte/macrophage content. Lymphocytes did not differ between the groups.
The investigators also explored the impact of metoprolol on the chemokine, monocyte chemoattractant protein–1 (MCP-1), as it has been shown to promote pulmonary fibrosis in late-stage ARDS.
They found that MCP-1 was significantly attenuated after 3 days of metoprolol treatment. At baseline, the median MCP-1 level was 298 pg/mL; on day 4 after metoprolol, it was 203 pg/mL (P = .009).
MCP-1 levels remained unchanged in control patients.
An elegant study
In an accompanying editorial, Mourad H. Senussi, MD, assistant professor at Baylor College of Medicine, Houston, wrote: “Although the study has a small sample size, we commend the authors, who attempt to shed light on the important pathophysiological underpinnings that help establish biological plausibility for this inexpensive, safe, and widely available medication.”
In an interview with this news organization, Dr. Senussi added that metoprolol is not itself something primarily used to treat COVID-19 per se. “Rather, the drug blunts the sympathetic-host response. There is a fine balance between that sympathetic surge that is helpful to the body, and then a sympathetic surge that if left unchecked, can lead to significant damage. And so, I think this study really shows that medications like metoprolol can help blunt that initial sympathetic effect.”
A larger study is “absolutely” warranted, he added, “this is a drug that is readily available, safe, and inexpensive. The study design here was simple and most importantly, showed biological plausibility.”
Dr. Senussi also noted that, although the benefit was noted in COVID-19 patients, the study sets the groundwork for further research in the use of beta-blockade in the critically ill. “Further studies are needed to elucidate and identify where along the inflammatory spectrum these critically ill patients lie, which patients would benefit from beta-blockers, and at what time point during their hospital stay.”
The MADRID-COVID authors and Dr. Senussi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a small study, intravenous administration of the beta-blocker metoprolol to critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) safely blunted lung inflammation associated with the disease.
Metoprolol administration also resulted in better oxygenation and fewer days on intensive mechanical ventilation and in the ICU, compared with no treatment.
These data suggest that metoprolol repurposing for the treatment of ARDS in COVID-19 patients is a safe and inexpensive strategy with the potential to improve outcomes, the researchers said.
“Metoprolol repurposing for the treatment of ARDS associated with COVID-19 is a safe and cheap intervention that can help to alleviate the massive personal and health care burden associated with the pandemic,” they concluded.
The results, from the MADRID-COVID pilot trial from Agustin Clemente-Moragon, BSc, Centro National de Investigaciones Cardiovasculares, Madrid, and colleagues, were published online Aug. 30, 2021, in the Journal of the American College of Cardiology.
In previous work, the researchers showed that metoprolol, but not other clinically available intravenous beta-blockers, abrogates neutrophil-driven exacerbated inflammation, neutrophil-platelet interaction, and formation of neutrophil extracellular traps in a mouse model of acute lung injury.
These results prompted the current pilot trial in 20 patients, ages 18-80 years, with COVID-19–associated ARDS.
Randomization was stratified by age (59 and younger vs. 60 and older), history of hypertension (yes or no), and circulating neutrophil counts (<6,000 vs. ≥6,000). Bronchoalveolar lavage (BAL) fluid and blood samples were obtained from patients at randomization and 24 hours after the third metoprolol dose in the treatment group, and on day 4 in controls.
Because of the cardiovascular effects of metoprolol, patients were monitored invasively and by echocardiography, the authors noted.
As expected, metoprolol significantly reduced heart rate (P < .01) and systolic blood pressure (P < .05), although both remained within the physiological range. Echocardiography showed no deterioration of cardiac function after metoprolol treatment.
To assess the ability of metoprolol to address neutrophil-mediated exacerbated lung inflammation, the researchers analyzed leukocyte populations in BAL samples by flow cytometry at baseline and on day 4.
At baseline, the metoprolol and control groups showed no differences in BAL neutrophil content. But on day 4, after 3 days of treatment with metoprolol, neutrophil content was significantly lower in the metoprolol group (median, 14.3 neutrophils/mcL) than in the control group (median, 397 neutrophils/mcL).
Metoprolol-treated patients also had lower total inflammatory-cell content and lower monocyte/macrophage content. Lymphocytes did not differ between the groups.
The investigators also explored the impact of metoprolol on the chemokine, monocyte chemoattractant protein–1 (MCP-1), as it has been shown to promote pulmonary fibrosis in late-stage ARDS.
They found that MCP-1 was significantly attenuated after 3 days of metoprolol treatment. At baseline, the median MCP-1 level was 298 pg/mL; on day 4 after metoprolol, it was 203 pg/mL (P = .009).
MCP-1 levels remained unchanged in control patients.
An elegant study
In an accompanying editorial, Mourad H. Senussi, MD, assistant professor at Baylor College of Medicine, Houston, wrote: “Although the study has a small sample size, we commend the authors, who attempt to shed light on the important pathophysiological underpinnings that help establish biological plausibility for this inexpensive, safe, and widely available medication.”
In an interview with this news organization, Dr. Senussi added that metoprolol is not itself something primarily used to treat COVID-19 per se. “Rather, the drug blunts the sympathetic-host response. There is a fine balance between that sympathetic surge that is helpful to the body, and then a sympathetic surge that if left unchecked, can lead to significant damage. And so, I think this study really shows that medications like metoprolol can help blunt that initial sympathetic effect.”
A larger study is “absolutely” warranted, he added, “this is a drug that is readily available, safe, and inexpensive. The study design here was simple and most importantly, showed biological plausibility.”
Dr. Senussi also noted that, although the benefit was noted in COVID-19 patients, the study sets the groundwork for further research in the use of beta-blockade in the critically ill. “Further studies are needed to elucidate and identify where along the inflammatory spectrum these critically ill patients lie, which patients would benefit from beta-blockers, and at what time point during their hospital stay.”
The MADRID-COVID authors and Dr. Senussi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a small study, intravenous administration of the beta-blocker metoprolol to critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) safely blunted lung inflammation associated with the disease.
Metoprolol administration also resulted in better oxygenation and fewer days on intensive mechanical ventilation and in the ICU, compared with no treatment.
These data suggest that metoprolol repurposing for the treatment of ARDS in COVID-19 patients is a safe and inexpensive strategy with the potential to improve outcomes, the researchers said.
“Metoprolol repurposing for the treatment of ARDS associated with COVID-19 is a safe and cheap intervention that can help to alleviate the massive personal and health care burden associated with the pandemic,” they concluded.
The results, from the MADRID-COVID pilot trial from Agustin Clemente-Moragon, BSc, Centro National de Investigaciones Cardiovasculares, Madrid, and colleagues, were published online Aug. 30, 2021, in the Journal of the American College of Cardiology.
In previous work, the researchers showed that metoprolol, but not other clinically available intravenous beta-blockers, abrogates neutrophil-driven exacerbated inflammation, neutrophil-platelet interaction, and formation of neutrophil extracellular traps in a mouse model of acute lung injury.
These results prompted the current pilot trial in 20 patients, ages 18-80 years, with COVID-19–associated ARDS.
Randomization was stratified by age (59 and younger vs. 60 and older), history of hypertension (yes or no), and circulating neutrophil counts (<6,000 vs. ≥6,000). Bronchoalveolar lavage (BAL) fluid and blood samples were obtained from patients at randomization and 24 hours after the third metoprolol dose in the treatment group, and on day 4 in controls.
Because of the cardiovascular effects of metoprolol, patients were monitored invasively and by echocardiography, the authors noted.
As expected, metoprolol significantly reduced heart rate (P < .01) and systolic blood pressure (P < .05), although both remained within the physiological range. Echocardiography showed no deterioration of cardiac function after metoprolol treatment.
To assess the ability of metoprolol to address neutrophil-mediated exacerbated lung inflammation, the researchers analyzed leukocyte populations in BAL samples by flow cytometry at baseline and on day 4.
At baseline, the metoprolol and control groups showed no differences in BAL neutrophil content. But on day 4, after 3 days of treatment with metoprolol, neutrophil content was significantly lower in the metoprolol group (median, 14.3 neutrophils/mcL) than in the control group (median, 397 neutrophils/mcL).
Metoprolol-treated patients also had lower total inflammatory-cell content and lower monocyte/macrophage content. Lymphocytes did not differ between the groups.
The investigators also explored the impact of metoprolol on the chemokine, monocyte chemoattractant protein–1 (MCP-1), as it has been shown to promote pulmonary fibrosis in late-stage ARDS.
They found that MCP-1 was significantly attenuated after 3 days of metoprolol treatment. At baseline, the median MCP-1 level was 298 pg/mL; on day 4 after metoprolol, it was 203 pg/mL (P = .009).
MCP-1 levels remained unchanged in control patients.
An elegant study
In an accompanying editorial, Mourad H. Senussi, MD, assistant professor at Baylor College of Medicine, Houston, wrote: “Although the study has a small sample size, we commend the authors, who attempt to shed light on the important pathophysiological underpinnings that help establish biological plausibility for this inexpensive, safe, and widely available medication.”
In an interview with this news organization, Dr. Senussi added that metoprolol is not itself something primarily used to treat COVID-19 per se. “Rather, the drug blunts the sympathetic-host response. There is a fine balance between that sympathetic surge that is helpful to the body, and then a sympathetic surge that if left unchecked, can lead to significant damage. And so, I think this study really shows that medications like metoprolol can help blunt that initial sympathetic effect.”
A larger study is “absolutely” warranted, he added, “this is a drug that is readily available, safe, and inexpensive. The study design here was simple and most importantly, showed biological plausibility.”
Dr. Senussi also noted that, although the benefit was noted in COVID-19 patients, the study sets the groundwork for further research in the use of beta-blockade in the critically ill. “Further studies are needed to elucidate and identify where along the inflammatory spectrum these critically ill patients lie, which patients would benefit from beta-blockers, and at what time point during their hospital stay.”
The MADRID-COVID authors and Dr. Senussi disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Flavonoid-rich foods, aided by gut bacteria, tied to lower BP
, an association that is partially explained by bacteria in an individual’s gut microbiome, new research suggests.
In a population-based study of more than 900 individuals, those with the highest intake of flavonoid-containing foods had significantly lower systolic blood pressure and pulse pressure, as well as greater gut microbial diversity, compared with those with the lowest intakes.
Up to 15% of this observed association was explained by the gut microbiome, suggesting that these microbes play a key role in metabolizing flavonoids to enhance their cardioprotective effects, according to the researchers.
The study was published online in the journal Hypertension.
“We know what we eat plays a critical role in shaping our gut microbiome, but little is known about the relative importance of plant foods and specific constituents called flavonoids,” lead researcher Aedin Cassidy, PhD, chair and professor of nutrition and medicine at the Institute for Global Food Security, Queen’s University, Belfast, Northern Ireland, said in an interview.
“Unlike many other food constituents, flavonoids are predominantly metabolized in the gut, suggesting that the gut microbiome may be more important in enhancing their biological activity than for other things we eat,” Dr. Cassidy said.
“There is mounting evidence from population-based studies and clinical trials that a higher intake of flavonoids and flavonoid-rich foods can improve heart health, but for the first time, we provide data highlighting the key role of the gut microbiome in explaining the association between such foods and blood pressure,” she noted. “This is one of the first studies to address this.”
For this analysis, Dr. Cassidy and her group sought to assess to what extent the composition of the gut microbiome might explain the association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure in a community-based sample of 904 individuals aged 25-82 years from Germany’s PopGen biobank.
The researchers evaluated participants’ food intake, gut microbiome, and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.
Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods, and flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.
Participants’ gut microbiome was assessed by fecal bacterial DNA extracted from stool samples.
After an overnight fast, participants’ blood pressure levels were measured three times in 3-minute intervals after an initial 5-minute rest period. Researchers also collected participants’ diet and lifestyle information.
Analysis of the data showed the following:
- Eating 1.5 servings of berries per day (about 1 cup) was associated with a 4.1–mm Hg reduction in systolic BP; 12% of this association was explained by gut microbiome factors.
- Drinking three glasses of red wine per week was associated with a 3.7–mm Hg reduction in systolic BP; 15% of this association was explained by the gut microbiome.
“These blood pressure–lowering effects are achievable with simple changes to the daily diet,” Dr. Cassidy said.
“Incorporating flavonoid-rich foods into the diet can have clinically relevant reductions in systolic blood pressure and pulse pressure, and a healthy gut microbiome is important to break down flavonoids to a more cardioprotective form,” she said.
“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Dr. Cassidy.
“A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”
‘Interesting’ data
“The data are interesting,” David Jenkins, MD, PhD, DSc, professor of medicine and nutrition at the University of Toronto, said in an interview.
“Berries and red wine appear to be associated with lower systolic blood pressures. Lower blood pressures have been found in general in people who consume more plant-based diets, especially those high in fruits and vegetables,” noted Dr. Jenkins, who was not involved with this study.
“Berries and grapes high in polyphenols may have many health benefits as antioxidants, and in a recent study have been shown to reduce cardiovascular mortality. The change in chronic microflora is also of interest as this will change with increased fruit and vegetable consumption,” he said.
Perhaps one word of caveat, Dr. Jenkins added: “Alcohol has been found to increase blood pressure and the risk of stroke. Presumably the beneficial effects as seen here were when wine is consumed in moderation.”
Supports recommendations
The study by Cassidy and colleagues supports the dietary recommendations from the American Heart Association (AHA) for heart health, Penny M. Kris-Etherton, PhD, RDN, professor of nutritional sciences, Penn State University, University Park, Pa., and chair, AHA Council on Lifestyle and Cardiometabolic Health, said in an interview.
“The AHA recommends a healthy dietary pattern that emphasizes a variety of plant foods including fruits, vegetables, whole grains, legumes, nuts, and seeds and is low in sodium, saturated fat, and added sugars. Lean protein foods, including plant protein foods, are recommended, and red meat should be limited. If alcohol is consumed it should be done in moderation,” Dr. Kris-Etherton said.
“Based on these AHA dietary recommendations, a wide variety of plant foods will promote consumption of many flavonoids that have demonstrated CVD benefits, such as lowering systolic blood pressure as reported by the authors, as well as promoting healthy endothelial function and having antithrombotic, anti-inflammatory and antioxidant effects,” she said in email.
“This recommended dietary pattern will have other cardiovascular health benefits, such as decreasing LDL cholesterol, due to its very healthy nutrient profile. The exciting new finding reported by Cassidy et al. is that the effects of dietary flavonoids on lowering systolic blood pressure are modulated by the gut microbiome,” Dr. Kris-Etherton said.
“Further research needs to be done to confirm these findings and to identify how different foods affect specific gut bacteria that benefit cardiovascular health.”
The research was funded by grants from the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Cassidy and Dr. Jenkins have disclosed no relevant financial relationships. Dr. Kris-Etherton is a spokesperson for the AHA.
A version of this article first appeared on Medscape.com.
, an association that is partially explained by bacteria in an individual’s gut microbiome, new research suggests.
In a population-based study of more than 900 individuals, those with the highest intake of flavonoid-containing foods had significantly lower systolic blood pressure and pulse pressure, as well as greater gut microbial diversity, compared with those with the lowest intakes.
Up to 15% of this observed association was explained by the gut microbiome, suggesting that these microbes play a key role in metabolizing flavonoids to enhance their cardioprotective effects, according to the researchers.
The study was published online in the journal Hypertension.
“We know what we eat plays a critical role in shaping our gut microbiome, but little is known about the relative importance of plant foods and specific constituents called flavonoids,” lead researcher Aedin Cassidy, PhD, chair and professor of nutrition and medicine at the Institute for Global Food Security, Queen’s University, Belfast, Northern Ireland, said in an interview.
“Unlike many other food constituents, flavonoids are predominantly metabolized in the gut, suggesting that the gut microbiome may be more important in enhancing their biological activity than for other things we eat,” Dr. Cassidy said.
“There is mounting evidence from population-based studies and clinical trials that a higher intake of flavonoids and flavonoid-rich foods can improve heart health, but for the first time, we provide data highlighting the key role of the gut microbiome in explaining the association between such foods and blood pressure,” she noted. “This is one of the first studies to address this.”
For this analysis, Dr. Cassidy and her group sought to assess to what extent the composition of the gut microbiome might explain the association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure in a community-based sample of 904 individuals aged 25-82 years from Germany’s PopGen biobank.
The researchers evaluated participants’ food intake, gut microbiome, and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.
Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods, and flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.
Participants’ gut microbiome was assessed by fecal bacterial DNA extracted from stool samples.
After an overnight fast, participants’ blood pressure levels were measured three times in 3-minute intervals after an initial 5-minute rest period. Researchers also collected participants’ diet and lifestyle information.
Analysis of the data showed the following:
- Eating 1.5 servings of berries per day (about 1 cup) was associated with a 4.1–mm Hg reduction in systolic BP; 12% of this association was explained by gut microbiome factors.
- Drinking three glasses of red wine per week was associated with a 3.7–mm Hg reduction in systolic BP; 15% of this association was explained by the gut microbiome.
“These blood pressure–lowering effects are achievable with simple changes to the daily diet,” Dr. Cassidy said.
“Incorporating flavonoid-rich foods into the diet can have clinically relevant reductions in systolic blood pressure and pulse pressure, and a healthy gut microbiome is important to break down flavonoids to a more cardioprotective form,” she said.
“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Dr. Cassidy.
“A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”
‘Interesting’ data
“The data are interesting,” David Jenkins, MD, PhD, DSc, professor of medicine and nutrition at the University of Toronto, said in an interview.
“Berries and red wine appear to be associated with lower systolic blood pressures. Lower blood pressures have been found in general in people who consume more plant-based diets, especially those high in fruits and vegetables,” noted Dr. Jenkins, who was not involved with this study.
“Berries and grapes high in polyphenols may have many health benefits as antioxidants, and in a recent study have been shown to reduce cardiovascular mortality. The change in chronic microflora is also of interest as this will change with increased fruit and vegetable consumption,” he said.
Perhaps one word of caveat, Dr. Jenkins added: “Alcohol has been found to increase blood pressure and the risk of stroke. Presumably the beneficial effects as seen here were when wine is consumed in moderation.”
Supports recommendations
The study by Cassidy and colleagues supports the dietary recommendations from the American Heart Association (AHA) for heart health, Penny M. Kris-Etherton, PhD, RDN, professor of nutritional sciences, Penn State University, University Park, Pa., and chair, AHA Council on Lifestyle and Cardiometabolic Health, said in an interview.
“The AHA recommends a healthy dietary pattern that emphasizes a variety of plant foods including fruits, vegetables, whole grains, legumes, nuts, and seeds and is low in sodium, saturated fat, and added sugars. Lean protein foods, including plant protein foods, are recommended, and red meat should be limited. If alcohol is consumed it should be done in moderation,” Dr. Kris-Etherton said.
“Based on these AHA dietary recommendations, a wide variety of plant foods will promote consumption of many flavonoids that have demonstrated CVD benefits, such as lowering systolic blood pressure as reported by the authors, as well as promoting healthy endothelial function and having antithrombotic, anti-inflammatory and antioxidant effects,” she said in email.
“This recommended dietary pattern will have other cardiovascular health benefits, such as decreasing LDL cholesterol, due to its very healthy nutrient profile. The exciting new finding reported by Cassidy et al. is that the effects of dietary flavonoids on lowering systolic blood pressure are modulated by the gut microbiome,” Dr. Kris-Etherton said.
“Further research needs to be done to confirm these findings and to identify how different foods affect specific gut bacteria that benefit cardiovascular health.”
The research was funded by grants from the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Cassidy and Dr. Jenkins have disclosed no relevant financial relationships. Dr. Kris-Etherton is a spokesperson for the AHA.
A version of this article first appeared on Medscape.com.
, an association that is partially explained by bacteria in an individual’s gut microbiome, new research suggests.
In a population-based study of more than 900 individuals, those with the highest intake of flavonoid-containing foods had significantly lower systolic blood pressure and pulse pressure, as well as greater gut microbial diversity, compared with those with the lowest intakes.
Up to 15% of this observed association was explained by the gut microbiome, suggesting that these microbes play a key role in metabolizing flavonoids to enhance their cardioprotective effects, according to the researchers.
The study was published online in the journal Hypertension.
“We know what we eat plays a critical role in shaping our gut microbiome, but little is known about the relative importance of plant foods and specific constituents called flavonoids,” lead researcher Aedin Cassidy, PhD, chair and professor of nutrition and medicine at the Institute for Global Food Security, Queen’s University, Belfast, Northern Ireland, said in an interview.
“Unlike many other food constituents, flavonoids are predominantly metabolized in the gut, suggesting that the gut microbiome may be more important in enhancing their biological activity than for other things we eat,” Dr. Cassidy said.
“There is mounting evidence from population-based studies and clinical trials that a higher intake of flavonoids and flavonoid-rich foods can improve heart health, but for the first time, we provide data highlighting the key role of the gut microbiome in explaining the association between such foods and blood pressure,” she noted. “This is one of the first studies to address this.”
For this analysis, Dr. Cassidy and her group sought to assess to what extent the composition of the gut microbiome might explain the association of habitual flavonoid and flavonoid-rich food intake with systolic and diastolic blood pressure in a community-based sample of 904 individuals aged 25-82 years from Germany’s PopGen biobank.
The researchers evaluated participants’ food intake, gut microbiome, and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.
Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods, and flavonoid values were assigned to foods according to United States Department of Agriculture data on flavonoid content in food.
Participants’ gut microbiome was assessed by fecal bacterial DNA extracted from stool samples.
After an overnight fast, participants’ blood pressure levels were measured three times in 3-minute intervals after an initial 5-minute rest period. Researchers also collected participants’ diet and lifestyle information.
Analysis of the data showed the following:
- Eating 1.5 servings of berries per day (about 1 cup) was associated with a 4.1–mm Hg reduction in systolic BP; 12% of this association was explained by gut microbiome factors.
- Drinking three glasses of red wine per week was associated with a 3.7–mm Hg reduction in systolic BP; 15% of this association was explained by the gut microbiome.
“These blood pressure–lowering effects are achievable with simple changes to the daily diet,” Dr. Cassidy said.
“Incorporating flavonoid-rich foods into the diet can have clinically relevant reductions in systolic blood pressure and pulse pressure, and a healthy gut microbiome is important to break down flavonoids to a more cardioprotective form,” she said.
“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Dr. Cassidy.
“A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”
‘Interesting’ data
“The data are interesting,” David Jenkins, MD, PhD, DSc, professor of medicine and nutrition at the University of Toronto, said in an interview.
“Berries and red wine appear to be associated with lower systolic blood pressures. Lower blood pressures have been found in general in people who consume more plant-based diets, especially those high in fruits and vegetables,” noted Dr. Jenkins, who was not involved with this study.
“Berries and grapes high in polyphenols may have many health benefits as antioxidants, and in a recent study have been shown to reduce cardiovascular mortality. The change in chronic microflora is also of interest as this will change with increased fruit and vegetable consumption,” he said.
Perhaps one word of caveat, Dr. Jenkins added: “Alcohol has been found to increase blood pressure and the risk of stroke. Presumably the beneficial effects as seen here were when wine is consumed in moderation.”
Supports recommendations
The study by Cassidy and colleagues supports the dietary recommendations from the American Heart Association (AHA) for heart health, Penny M. Kris-Etherton, PhD, RDN, professor of nutritional sciences, Penn State University, University Park, Pa., and chair, AHA Council on Lifestyle and Cardiometabolic Health, said in an interview.
“The AHA recommends a healthy dietary pattern that emphasizes a variety of plant foods including fruits, vegetables, whole grains, legumes, nuts, and seeds and is low in sodium, saturated fat, and added sugars. Lean protein foods, including plant protein foods, are recommended, and red meat should be limited. If alcohol is consumed it should be done in moderation,” Dr. Kris-Etherton said.
“Based on these AHA dietary recommendations, a wide variety of plant foods will promote consumption of many flavonoids that have demonstrated CVD benefits, such as lowering systolic blood pressure as reported by the authors, as well as promoting healthy endothelial function and having antithrombotic, anti-inflammatory and antioxidant effects,” she said in email.
“This recommended dietary pattern will have other cardiovascular health benefits, such as decreasing LDL cholesterol, due to its very healthy nutrient profile. The exciting new finding reported by Cassidy et al. is that the effects of dietary flavonoids on lowering systolic blood pressure are modulated by the gut microbiome,” Dr. Kris-Etherton said.
“Further research needs to be done to confirm these findings and to identify how different foods affect specific gut bacteria that benefit cardiovascular health.”
The research was funded by grants from the German Research Foundation and the German Federal Ministry of Education and Research. Dr. Cassidy and Dr. Jenkins have disclosed no relevant financial relationships. Dr. Kris-Etherton is a spokesperson for the AHA.
A version of this article first appeared on Medscape.com.
Plant-based lignan intake linked to lower CHD risk
Consumption of a plant-based diet rich in lignans is associated with a lower risk of coronary heart disease (CHD), new research suggests.
In a prospective cohort study that followed almost 214,108 men and women who were free of CHD and cancer at baseline, increased long-term intake of lignans, polyphenolic substances produced by plants, was associated with significantly lower risk of total CHD in both men and women.
The benefit was increased in participants with a greater intake of fiber, suggesting that synergistic effects between the two might exist in relation to CHD reduction.
The results were published online in the Journal of the American College of Cardiology.
“Lignan is an estrogen-like molecule, so it exerts some estrogenic effects which are cardioprotective. It also has anti-inflammatory properties,” first author Yang Hu, ScD, a research fellow at the Harvard School of Public Health, Boston, said in an interview.
“Our results that showed an inverse association between lignan consumption and heart disease risk were expected, because it is known that lignans, which are predominantly from plant-based foods, like whole grains, fruit, vegetables, red wine, and coffee, are all associated with lower CHD risk,” Dr. Hu said.
What is novel about the current study is that it established a threshold for lignan consumption, above which there is no CHD benefit, he said.
“It is not a matter of the more you consume, the lower your risk. There is a certain amount of lignan you have to reach, after which there is no more benefit,” Dr. Hu said.
Dr. Hu and associates prospectively followed 214,108 men and women in three cohorts who did not have cardiovascular disease or cancer at baseline. The cohorts were the Health Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II.
Diets were assessed using the Food Frequency Questionnaire every 2-4 years at follow-up visits.
During 5.5 million person-years of follow-up, Dr. Hu and associates documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarctions and 3,961 fatal CHD cases.
The results showed that higher total lignan intake, and all individual lignan intake as well, were associated with significantly lower risk of total CHD.
Participants with higher total lignan intake were older and had more favorable health and lifestyle profiles including lower body mass index, lower prevalence of hypertension and hypercholesterolemia, high levels of physical activity, and better diet quality.
Overall, the pooled hazard ratios of CHD were 0.85 (95% confidence interval, 0.79-0.92) for total lignans, 0.76 (95% CI, 0.71-0.82) for matairesinol, 0.87 (95% CI, 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI, 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83- 0.95) for lariciresinol (all P values for trend ≤ .003).
In addition, nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: The risk reduction plateaued at intakes above approximately 300 mcg/d for total lignan; 10 mcg/d for matairesinol, and 100 mcg/d for secoisolariciresinol.
The inverse associations for total lignan intake were more apparent among participants with higher total fiber intake.
In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.
Dr. Hu said a next avenue of research will explore the synergistic association between lignans and fiber in further lowering CHD risk.
Lignans are exclusively metabolized by gut microbiota, Dr. Hu noted. “This opens another avenue of research because we can take further steps to see how the gut microbiota compositions and fiber interact with the production of lignans and how these might affect disease risk for other conditions, such as diabetes.”
An important study
“The evidence is building that there is an association between polyphenol intake and chronic disease, especially for CVD [cardiovascular disease],” David J.A. Jenkins, MD, PhD, and colleagues wrote in an accompanying editorial.
“Plant polyphenols may be important components of healthy plant-based diets that contribute to freedom from chronic diseases such as CVD, diabetes, and possibly cancer and so are associated with a reduction in all-cause mortality,” they wrote.
“I think this is an important study even though the results are not unexpected,” Dr. Jenkins, professor in the departments of medicine and nutritional sciences at the University of Toronto, said in an interview.
“We do know that plant polyphenols are important sources of antioxidants and may have many protective roles in preventing destruction of proteins and DNA destruction, so the results here reinforce very strongly the concept of plant foods and their importance in the diet,” he said.
The data reaffirmed the value of eating a variety of plant foods and eating them in a less processed form, because they have higher amounts of their phenolic compounds, Dr. Jenkins said.
“Things like wheat, oats, barley, [and] whole grain foods will have more phenolic components with them, as do fruits and vegetables,” he said.
Dr. Hu and Dr. Jenkins disclosed no relevant financial relationships.
Aversion of this article first appeared on Medscape.com.
Consumption of a plant-based diet rich in lignans is associated with a lower risk of coronary heart disease (CHD), new research suggests.
In a prospective cohort study that followed almost 214,108 men and women who were free of CHD and cancer at baseline, increased long-term intake of lignans, polyphenolic substances produced by plants, was associated with significantly lower risk of total CHD in both men and women.
The benefit was increased in participants with a greater intake of fiber, suggesting that synergistic effects between the two might exist in relation to CHD reduction.
The results were published online in the Journal of the American College of Cardiology.
“Lignan is an estrogen-like molecule, so it exerts some estrogenic effects which are cardioprotective. It also has anti-inflammatory properties,” first author Yang Hu, ScD, a research fellow at the Harvard School of Public Health, Boston, said in an interview.
“Our results that showed an inverse association between lignan consumption and heart disease risk were expected, because it is known that lignans, which are predominantly from plant-based foods, like whole grains, fruit, vegetables, red wine, and coffee, are all associated with lower CHD risk,” Dr. Hu said.
What is novel about the current study is that it established a threshold for lignan consumption, above which there is no CHD benefit, he said.
“It is not a matter of the more you consume, the lower your risk. There is a certain amount of lignan you have to reach, after which there is no more benefit,” Dr. Hu said.
Dr. Hu and associates prospectively followed 214,108 men and women in three cohorts who did not have cardiovascular disease or cancer at baseline. The cohorts were the Health Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II.
Diets were assessed using the Food Frequency Questionnaire every 2-4 years at follow-up visits.
During 5.5 million person-years of follow-up, Dr. Hu and associates documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarctions and 3,961 fatal CHD cases.
The results showed that higher total lignan intake, and all individual lignan intake as well, were associated with significantly lower risk of total CHD.
Participants with higher total lignan intake were older and had more favorable health and lifestyle profiles including lower body mass index, lower prevalence of hypertension and hypercholesterolemia, high levels of physical activity, and better diet quality.
Overall, the pooled hazard ratios of CHD were 0.85 (95% confidence interval, 0.79-0.92) for total lignans, 0.76 (95% CI, 0.71-0.82) for matairesinol, 0.87 (95% CI, 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI, 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83- 0.95) for lariciresinol (all P values for trend ≤ .003).
In addition, nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: The risk reduction plateaued at intakes above approximately 300 mcg/d for total lignan; 10 mcg/d for matairesinol, and 100 mcg/d for secoisolariciresinol.
The inverse associations for total lignan intake were more apparent among participants with higher total fiber intake.
In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.
Dr. Hu said a next avenue of research will explore the synergistic association between lignans and fiber in further lowering CHD risk.
Lignans are exclusively metabolized by gut microbiota, Dr. Hu noted. “This opens another avenue of research because we can take further steps to see how the gut microbiota compositions and fiber interact with the production of lignans and how these might affect disease risk for other conditions, such as diabetes.”
An important study
“The evidence is building that there is an association between polyphenol intake and chronic disease, especially for CVD [cardiovascular disease],” David J.A. Jenkins, MD, PhD, and colleagues wrote in an accompanying editorial.
“Plant polyphenols may be important components of healthy plant-based diets that contribute to freedom from chronic diseases such as CVD, diabetes, and possibly cancer and so are associated with a reduction in all-cause mortality,” they wrote.
“I think this is an important study even though the results are not unexpected,” Dr. Jenkins, professor in the departments of medicine and nutritional sciences at the University of Toronto, said in an interview.
“We do know that plant polyphenols are important sources of antioxidants and may have many protective roles in preventing destruction of proteins and DNA destruction, so the results here reinforce very strongly the concept of plant foods and their importance in the diet,” he said.
The data reaffirmed the value of eating a variety of plant foods and eating them in a less processed form, because they have higher amounts of their phenolic compounds, Dr. Jenkins said.
“Things like wheat, oats, barley, [and] whole grain foods will have more phenolic components with them, as do fruits and vegetables,” he said.
Dr. Hu and Dr. Jenkins disclosed no relevant financial relationships.
Aversion of this article first appeared on Medscape.com.
Consumption of a plant-based diet rich in lignans is associated with a lower risk of coronary heart disease (CHD), new research suggests.
In a prospective cohort study that followed almost 214,108 men and women who were free of CHD and cancer at baseline, increased long-term intake of lignans, polyphenolic substances produced by plants, was associated with significantly lower risk of total CHD in both men and women.
The benefit was increased in participants with a greater intake of fiber, suggesting that synergistic effects between the two might exist in relation to CHD reduction.
The results were published online in the Journal of the American College of Cardiology.
“Lignan is an estrogen-like molecule, so it exerts some estrogenic effects which are cardioprotective. It also has anti-inflammatory properties,” first author Yang Hu, ScD, a research fellow at the Harvard School of Public Health, Boston, said in an interview.
“Our results that showed an inverse association between lignan consumption and heart disease risk were expected, because it is known that lignans, which are predominantly from plant-based foods, like whole grains, fruit, vegetables, red wine, and coffee, are all associated with lower CHD risk,” Dr. Hu said.
What is novel about the current study is that it established a threshold for lignan consumption, above which there is no CHD benefit, he said.
“It is not a matter of the more you consume, the lower your risk. There is a certain amount of lignan you have to reach, after which there is no more benefit,” Dr. Hu said.
Dr. Hu and associates prospectively followed 214,108 men and women in three cohorts who did not have cardiovascular disease or cancer at baseline. The cohorts were the Health Professionals Follow-Up Study, Nurses’ Health Study, and Nurses’ Health Study II.
Diets were assessed using the Food Frequency Questionnaire every 2-4 years at follow-up visits.
During 5.5 million person-years of follow-up, Dr. Hu and associates documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarctions and 3,961 fatal CHD cases.
The results showed that higher total lignan intake, and all individual lignan intake as well, were associated with significantly lower risk of total CHD.
Participants with higher total lignan intake were older and had more favorable health and lifestyle profiles including lower body mass index, lower prevalence of hypertension and hypercholesterolemia, high levels of physical activity, and better diet quality.
Overall, the pooled hazard ratios of CHD were 0.85 (95% confidence interval, 0.79-0.92) for total lignans, 0.76 (95% CI, 0.71-0.82) for matairesinol, 0.87 (95% CI, 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI, 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83- 0.95) for lariciresinol (all P values for trend ≤ .003).
In addition, nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: The risk reduction plateaued at intakes above approximately 300 mcg/d for total lignan; 10 mcg/d for matairesinol, and 100 mcg/d for secoisolariciresinol.
The inverse associations for total lignan intake were more apparent among participants with higher total fiber intake.
In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.
Dr. Hu said a next avenue of research will explore the synergistic association between lignans and fiber in further lowering CHD risk.
Lignans are exclusively metabolized by gut microbiota, Dr. Hu noted. “This opens another avenue of research because we can take further steps to see how the gut microbiota compositions and fiber interact with the production of lignans and how these might affect disease risk for other conditions, such as diabetes.”
An important study
“The evidence is building that there is an association between polyphenol intake and chronic disease, especially for CVD [cardiovascular disease],” David J.A. Jenkins, MD, PhD, and colleagues wrote in an accompanying editorial.
“Plant polyphenols may be important components of healthy plant-based diets that contribute to freedom from chronic diseases such as CVD, diabetes, and possibly cancer and so are associated with a reduction in all-cause mortality,” they wrote.
“I think this is an important study even though the results are not unexpected,” Dr. Jenkins, professor in the departments of medicine and nutritional sciences at the University of Toronto, said in an interview.
“We do know that plant polyphenols are important sources of antioxidants and may have many protective roles in preventing destruction of proteins and DNA destruction, so the results here reinforce very strongly the concept of plant foods and their importance in the diet,” he said.
The data reaffirmed the value of eating a variety of plant foods and eating them in a less processed form, because they have higher amounts of their phenolic compounds, Dr. Jenkins said.
“Things like wheat, oats, barley, [and] whole grain foods will have more phenolic components with them, as do fruits and vegetables,” he said.
Dr. Hu and Dr. Jenkins disclosed no relevant financial relationships.
Aversion of this article first appeared on Medscape.com.
Rising meth-related heart failure admissions a ‘crisis,’ costly for society
Rates of heart failure (HF) caused by methamphetamine abuse are climbing quickly in the western United States, at great financial and societal cost, suggests an analysis that documents the trends in California over a recent decade.
In the new study, methamphetamine-associated HF (meth-HF) admissions in the state rose by 585% between 2008 and 2018, and charges related those hospitalizations jumped 840%. Cases of HF unrelated to meth fell by 6% during the same period.
The recent explosion in meth-HF hospitalizations has also been costly for society in general, because most cases are younger adults in their most productive, prime earning years, Susan X. Zhao, MD, Santa Clara Valley Medical Center, San Jose, Calif., said in an interview.
“Over the past 11 years, especially since 2018, it has really started to take off, with a pretty dramatic rise. And it happened without much attention, because when we think about drugs, we think about acute overdose and not so much about the chronic, smoldering, long-term effects,” said Dr. Zhao, who is lead author on the study published July 13, 2021, in Circulation: Cardiovascular Quality and Outcomes.
“It’s really affecting a section of the population that is not supposed to be having heart failure problems. I think it is going to continue for the next decade until we put a stop to the parent problem, which is methamphetamine,” Dr. Zhao said. “We’re at the beginning, even though the rise has been pretty dramatic. The worst is yet to come.”
Under the radar
Methamphetamine-associated HF has been a growing problem for many years but has largely been “flying under the radar” because HF hospitalization data focus on Medicare-age patients, not the overwhelmingly younger meth-HF population, the report notes.
“We have to get this message out. Many of my patients with meth heart failure had no idea this would happen to them. They didn’t know,” Dr. Zhao said. “Once I tell them that this is what methamphetamines will do to you after years and years of use, they say they wish someone had told them.”
Dr. Zhao and colleagues looked at HF admission data collected by California’s Health and Human Services Agency to assess meth-HF trends and disease burden. They identified 1,033,076 HF hospitalizations during the decade, of which 42,565 (4.12%) were for meth-HF.
Patients hospitalized with meth-HF had a mean age of 49.6 years, compared with 72.2 for the other patients admitted with HF (P < .001). Virtually all of the patients hospitalized for meth-HF were younger than 65 years: 94.5%, compared with 30% for the other HF patients (P < .001).
Hospitalized patients with meth-HF were mostly men, their prevalence of 80% contrasting with 52.4% for patients with non–meth-related HF (P < .001).
Rates of hospitalization for meth-HF steadily increased during the study period. The age-adjusted rate of meth-HF hospitalization per 100,000 rose from 4.1 in 2008 to 28.1 in 2018. The rate of hospitalization for HF unrelated to meth actually declined, going from 342.3 in 2008 to 321.6 in 2018.
Charges for hospitalizations related to meth-HF shot up more than eight times, from $41.5 million in 2008 to $390.2 million in 2018. In contrast, charges for other HF hospitalizations rose by only 82%, from $3.5 billion to $6.3 billion.
Multiple layers of prevention
Dr. Zhao proposed ways that clinicians can communicate with their patients who are using or considering to use meth. “There are multiple layers of prevention. For people who are thinking of using meth, they need to get the message that something really bad can happen to them years down the road. They’re not going to die from it overnight, but it will damage the heart slowly,” she said.
The next layer of prevention can potentially help meth users who have not yet developed heart problems, Dr. Zhao said. “This would be the time to say, ‘you’re so lucky, your heart is still good. It’s time to stop because people like you, a few years from now are going to die prematurely from a very horrible, very suffering kind of death’.”
Importantly, in meth users who have already developed HF, even then it may not be too late to reverse the cardiomyopathy and symptoms. For up to a third of people with established meth-HF, “if they stop using meth, if they take good cardiac medications, and if the heart failure is in an early enough course, their heart can entirely revert to normal,” Dr. Zhao said, citing an earlier work from her and her colleagues.
Currently, methamphetamine abuse has taken especially strong root in rural areas in California and the Midwest. But Dr. Zhao predicts it will soon become prevalent throughout the United States.
Spotlight on an ‘epidemic’
The rapid growth of the methamphetamine “epidemic” has been well-documented in the United States and around the world, observed an accompanying editorial from Pavan Reddy, MD, Icahn School of Medicine at Mount Sinai Morningside, New York, and Uri Elkayam, MD, University of Southern California, Los Angeles.
They contend that more attention has been given to opioid overdose deaths; meth abuse does not seem to command the same attention, likely because meth is not as strongly associated with acute overdose.
But meth, wrote Dr. Reddy and Dr. Elkayam, “is a different drug with its own M.O., equally dangerous and costly to society but more insidious in nature, its effects potentially causing decades of mental and physical debilitation before ending in premature death.”
The current study “has turned a spotlight on a public health crisis that has grown unfettered for over 2 decades,” and is a call for the “medical community to recognize and manage cases of meth-HF with a comprehensive approach that addresses both mental and physical illness,” they concluded. “Only then can we hope to properly help these patients and with that, reduce the socioeconomic burden of meth-HF.”
A quietly building crisis
The sharp rise in meth-HF hospitalizations is an expected reflection of the methamphetamine crisis, which has been quietly building over the last few years, addiction psychiatrist Corneliu N. Stanciu, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said in an interview.
“This new version of methamphetamines looks like ice and is more potent and toxic than former versions traditionally made in home-built labs,” he said. Lately the vast majority of methamphetamines in the United States have come from Mexico, are less expensive with higher purity, “and can be manufactured in greater quantities.”
Some patients with opioid use disorder (OUD) also inject methamphetamines, which can make OUD treatment clinics good places to screen for meth abuse and educate about its cardiovascular implications, Dr. Stanciu said.
“Just as addiction treatment centers present an opportunity to implement cardiac screening and referrals,” he said, “cardiology visits and hospitalizations such as those for meth-HF also present a golden opportunity for involvement of substance use disorder interventions and referrals to get patients into treatment and prevent further damage through ongoing use.”
Dr. Zhao, Dr. Reddy, Dr. Eklayam, and Dr. Stanciu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of heart failure (HF) caused by methamphetamine abuse are climbing quickly in the western United States, at great financial and societal cost, suggests an analysis that documents the trends in California over a recent decade.
In the new study, methamphetamine-associated HF (meth-HF) admissions in the state rose by 585% between 2008 and 2018, and charges related those hospitalizations jumped 840%. Cases of HF unrelated to meth fell by 6% during the same period.
The recent explosion in meth-HF hospitalizations has also been costly for society in general, because most cases are younger adults in their most productive, prime earning years, Susan X. Zhao, MD, Santa Clara Valley Medical Center, San Jose, Calif., said in an interview.
“Over the past 11 years, especially since 2018, it has really started to take off, with a pretty dramatic rise. And it happened without much attention, because when we think about drugs, we think about acute overdose and not so much about the chronic, smoldering, long-term effects,” said Dr. Zhao, who is lead author on the study published July 13, 2021, in Circulation: Cardiovascular Quality and Outcomes.
“It’s really affecting a section of the population that is not supposed to be having heart failure problems. I think it is going to continue for the next decade until we put a stop to the parent problem, which is methamphetamine,” Dr. Zhao said. “We’re at the beginning, even though the rise has been pretty dramatic. The worst is yet to come.”
Under the radar
Methamphetamine-associated HF has been a growing problem for many years but has largely been “flying under the radar” because HF hospitalization data focus on Medicare-age patients, not the overwhelmingly younger meth-HF population, the report notes.
“We have to get this message out. Many of my patients with meth heart failure had no idea this would happen to them. They didn’t know,” Dr. Zhao said. “Once I tell them that this is what methamphetamines will do to you after years and years of use, they say they wish someone had told them.”
Dr. Zhao and colleagues looked at HF admission data collected by California’s Health and Human Services Agency to assess meth-HF trends and disease burden. They identified 1,033,076 HF hospitalizations during the decade, of which 42,565 (4.12%) were for meth-HF.
Patients hospitalized with meth-HF had a mean age of 49.6 years, compared with 72.2 for the other patients admitted with HF (P < .001). Virtually all of the patients hospitalized for meth-HF were younger than 65 years: 94.5%, compared with 30% for the other HF patients (P < .001).
Hospitalized patients with meth-HF were mostly men, their prevalence of 80% contrasting with 52.4% for patients with non–meth-related HF (P < .001).
Rates of hospitalization for meth-HF steadily increased during the study period. The age-adjusted rate of meth-HF hospitalization per 100,000 rose from 4.1 in 2008 to 28.1 in 2018. The rate of hospitalization for HF unrelated to meth actually declined, going from 342.3 in 2008 to 321.6 in 2018.
Charges for hospitalizations related to meth-HF shot up more than eight times, from $41.5 million in 2008 to $390.2 million in 2018. In contrast, charges for other HF hospitalizations rose by only 82%, from $3.5 billion to $6.3 billion.
Multiple layers of prevention
Dr. Zhao proposed ways that clinicians can communicate with their patients who are using or considering to use meth. “There are multiple layers of prevention. For people who are thinking of using meth, they need to get the message that something really bad can happen to them years down the road. They’re not going to die from it overnight, but it will damage the heart slowly,” she said.
The next layer of prevention can potentially help meth users who have not yet developed heart problems, Dr. Zhao said. “This would be the time to say, ‘you’re so lucky, your heart is still good. It’s time to stop because people like you, a few years from now are going to die prematurely from a very horrible, very suffering kind of death’.”
Importantly, in meth users who have already developed HF, even then it may not be too late to reverse the cardiomyopathy and symptoms. For up to a third of people with established meth-HF, “if they stop using meth, if they take good cardiac medications, and if the heart failure is in an early enough course, their heart can entirely revert to normal,” Dr. Zhao said, citing an earlier work from her and her colleagues.
Currently, methamphetamine abuse has taken especially strong root in rural areas in California and the Midwest. But Dr. Zhao predicts it will soon become prevalent throughout the United States.
Spotlight on an ‘epidemic’
The rapid growth of the methamphetamine “epidemic” has been well-documented in the United States and around the world, observed an accompanying editorial from Pavan Reddy, MD, Icahn School of Medicine at Mount Sinai Morningside, New York, and Uri Elkayam, MD, University of Southern California, Los Angeles.
They contend that more attention has been given to opioid overdose deaths; meth abuse does not seem to command the same attention, likely because meth is not as strongly associated with acute overdose.
But meth, wrote Dr. Reddy and Dr. Elkayam, “is a different drug with its own M.O., equally dangerous and costly to society but more insidious in nature, its effects potentially causing decades of mental and physical debilitation before ending in premature death.”
The current study “has turned a spotlight on a public health crisis that has grown unfettered for over 2 decades,” and is a call for the “medical community to recognize and manage cases of meth-HF with a comprehensive approach that addresses both mental and physical illness,” they concluded. “Only then can we hope to properly help these patients and with that, reduce the socioeconomic burden of meth-HF.”
A quietly building crisis
The sharp rise in meth-HF hospitalizations is an expected reflection of the methamphetamine crisis, which has been quietly building over the last few years, addiction psychiatrist Corneliu N. Stanciu, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said in an interview.
“This new version of methamphetamines looks like ice and is more potent and toxic than former versions traditionally made in home-built labs,” he said. Lately the vast majority of methamphetamines in the United States have come from Mexico, are less expensive with higher purity, “and can be manufactured in greater quantities.”
Some patients with opioid use disorder (OUD) also inject methamphetamines, which can make OUD treatment clinics good places to screen for meth abuse and educate about its cardiovascular implications, Dr. Stanciu said.
“Just as addiction treatment centers present an opportunity to implement cardiac screening and referrals,” he said, “cardiology visits and hospitalizations such as those for meth-HF also present a golden opportunity for involvement of substance use disorder interventions and referrals to get patients into treatment and prevent further damage through ongoing use.”
Dr. Zhao, Dr. Reddy, Dr. Eklayam, and Dr. Stanciu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rates of heart failure (HF) caused by methamphetamine abuse are climbing quickly in the western United States, at great financial and societal cost, suggests an analysis that documents the trends in California over a recent decade.
In the new study, methamphetamine-associated HF (meth-HF) admissions in the state rose by 585% between 2008 and 2018, and charges related those hospitalizations jumped 840%. Cases of HF unrelated to meth fell by 6% during the same period.
The recent explosion in meth-HF hospitalizations has also been costly for society in general, because most cases are younger adults in their most productive, prime earning years, Susan X. Zhao, MD, Santa Clara Valley Medical Center, San Jose, Calif., said in an interview.
“Over the past 11 years, especially since 2018, it has really started to take off, with a pretty dramatic rise. And it happened without much attention, because when we think about drugs, we think about acute overdose and not so much about the chronic, smoldering, long-term effects,” said Dr. Zhao, who is lead author on the study published July 13, 2021, in Circulation: Cardiovascular Quality and Outcomes.
“It’s really affecting a section of the population that is not supposed to be having heart failure problems. I think it is going to continue for the next decade until we put a stop to the parent problem, which is methamphetamine,” Dr. Zhao said. “We’re at the beginning, even though the rise has been pretty dramatic. The worst is yet to come.”
Under the radar
Methamphetamine-associated HF has been a growing problem for many years but has largely been “flying under the radar” because HF hospitalization data focus on Medicare-age patients, not the overwhelmingly younger meth-HF population, the report notes.
“We have to get this message out. Many of my patients with meth heart failure had no idea this would happen to them. They didn’t know,” Dr. Zhao said. “Once I tell them that this is what methamphetamines will do to you after years and years of use, they say they wish someone had told them.”
Dr. Zhao and colleagues looked at HF admission data collected by California’s Health and Human Services Agency to assess meth-HF trends and disease burden. They identified 1,033,076 HF hospitalizations during the decade, of which 42,565 (4.12%) were for meth-HF.
Patients hospitalized with meth-HF had a mean age of 49.6 years, compared with 72.2 for the other patients admitted with HF (P < .001). Virtually all of the patients hospitalized for meth-HF were younger than 65 years: 94.5%, compared with 30% for the other HF patients (P < .001).
Hospitalized patients with meth-HF were mostly men, their prevalence of 80% contrasting with 52.4% for patients with non–meth-related HF (P < .001).
Rates of hospitalization for meth-HF steadily increased during the study period. The age-adjusted rate of meth-HF hospitalization per 100,000 rose from 4.1 in 2008 to 28.1 in 2018. The rate of hospitalization for HF unrelated to meth actually declined, going from 342.3 in 2008 to 321.6 in 2018.
Charges for hospitalizations related to meth-HF shot up more than eight times, from $41.5 million in 2008 to $390.2 million in 2018. In contrast, charges for other HF hospitalizations rose by only 82%, from $3.5 billion to $6.3 billion.
Multiple layers of prevention
Dr. Zhao proposed ways that clinicians can communicate with their patients who are using or considering to use meth. “There are multiple layers of prevention. For people who are thinking of using meth, they need to get the message that something really bad can happen to them years down the road. They’re not going to die from it overnight, but it will damage the heart slowly,” she said.
The next layer of prevention can potentially help meth users who have not yet developed heart problems, Dr. Zhao said. “This would be the time to say, ‘you’re so lucky, your heart is still good. It’s time to stop because people like you, a few years from now are going to die prematurely from a very horrible, very suffering kind of death’.”
Importantly, in meth users who have already developed HF, even then it may not be too late to reverse the cardiomyopathy and symptoms. For up to a third of people with established meth-HF, “if they stop using meth, if they take good cardiac medications, and if the heart failure is in an early enough course, their heart can entirely revert to normal,” Dr. Zhao said, citing an earlier work from her and her colleagues.
Currently, methamphetamine abuse has taken especially strong root in rural areas in California and the Midwest. But Dr. Zhao predicts it will soon become prevalent throughout the United States.
Spotlight on an ‘epidemic’
The rapid growth of the methamphetamine “epidemic” has been well-documented in the United States and around the world, observed an accompanying editorial from Pavan Reddy, MD, Icahn School of Medicine at Mount Sinai Morningside, New York, and Uri Elkayam, MD, University of Southern California, Los Angeles.
They contend that more attention has been given to opioid overdose deaths; meth abuse does not seem to command the same attention, likely because meth is not as strongly associated with acute overdose.
But meth, wrote Dr. Reddy and Dr. Elkayam, “is a different drug with its own M.O., equally dangerous and costly to society but more insidious in nature, its effects potentially causing decades of mental and physical debilitation before ending in premature death.”
The current study “has turned a spotlight on a public health crisis that has grown unfettered for over 2 decades,” and is a call for the “medical community to recognize and manage cases of meth-HF with a comprehensive approach that addresses both mental and physical illness,” they concluded. “Only then can we hope to properly help these patients and with that, reduce the socioeconomic burden of meth-HF.”
A quietly building crisis
The sharp rise in meth-HF hospitalizations is an expected reflection of the methamphetamine crisis, which has been quietly building over the last few years, addiction psychiatrist Corneliu N. Stanciu, MD, Dartmouth-Hitchcock Medical Center, Lebanon, N.H., said in an interview.
“This new version of methamphetamines looks like ice and is more potent and toxic than former versions traditionally made in home-built labs,” he said. Lately the vast majority of methamphetamines in the United States have come from Mexico, are less expensive with higher purity, “and can be manufactured in greater quantities.”
Some patients with opioid use disorder (OUD) also inject methamphetamines, which can make OUD treatment clinics good places to screen for meth abuse and educate about its cardiovascular implications, Dr. Stanciu said.
“Just as addiction treatment centers present an opportunity to implement cardiac screening and referrals,” he said, “cardiology visits and hospitalizations such as those for meth-HF also present a golden opportunity for involvement of substance use disorder interventions and referrals to get patients into treatment and prevent further damage through ongoing use.”
Dr. Zhao, Dr. Reddy, Dr. Eklayam, and Dr. Stanciu report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CABANA: Ablation bests drugs for AFib in racial/ethnic minorities
CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.
But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.
In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.
The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.
“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.
“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.
“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”
The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).
Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).
The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.
Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).
The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).
However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).
The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.
Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”
Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.
Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.
“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.
“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.
Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.
“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”
Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.
A version of this article first appeared on Medscape.com.
CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.
But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.
In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.
The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.
“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.
“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.
“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”
The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).
Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).
The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.
Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).
The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).
However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).
The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.
Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”
Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.
Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.
“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.
“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.
Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.
“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”
Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.
A version of this article first appeared on Medscape.com.
CABANA, which was undertaken to compare catheter ablation and rate-control or rhythm-control drug therapy for AFib, concluded there was no significant difference between the two strategies in improving the trial’s composite primary outcome of death, disabling stroke, serious bleeding, or cardiac arrest.
But a closer look at a subgroup of participants reveals an important difference in outcome among racial and ethnic minorities.
In that group, which made up about 10% of the CABANA study population, catheter ablation was significantly better at treating AFib than was drug therapy, producing roughly a 70% relative reduction in the primary endpoint and all-cause mortality.
The benefit for catheter ablation, which was not seen in the nonminority participants, appeared to be due to worse outcomes with drug therapy, the investigators report in an article published July 5 in the Journal of the American College of Cardiology.
“The study really highlights the importance of trying to secure an inclusive and diverse population in clinical trials,” lead author Kevin L. Thomas, MD, Duke University, Durham, N.C., said in an interview.
“When we focused on the racial and ethnic minorities who were included in CABANA, the findings were different. This was a surprise,” Dr. Thomas said.
“The findings from the secondary analysis of CABANA suggest that racial and ethnic minorities that are treated with drugs compared with ablation do worse,” he said. “If we can validate this in a larger sample of patients and this does in fact turn out to be true, then we would change how we practice medicine. We would have discussions with these populations about the benefits of ablation over drugs, and this would be important information to help guide our practice.”
The investigators analyzed data from 1,280 participants enrolled in the North American arm of CABANA. Of these, 127 (9.9%) were of racial or ethnic minorities, as defined by the National Institutes of Health, and were randomly assigned to receive ablation (n = 62) or drug therapy (n = 65).
Compared with nonminorities, participants of racial and ethnic minorities were younger (median age, 65.5 years, vs. 68.5 years) and were more likely to have NYHA functional class greater than or equal to II symptoms (37.0% vs. 22.0%), hypertension (92.1% vs. 76.8%), and an ejection fraction less than 40% (20.8% vs. 7.1%).
The overall median follow-up was 54.9 months. Among ethnic and minority participants, the median follow-up was 48 months, compared with 55.5 months for the nonminority participants.
Although there was no significant difference in the primary composite endpoint in the main CABANA trial, among racial and ethnic minorities treated with ablation, there was a 68% relative reduction in the trial’s primary endpoint (adjusted hazard ratio, 0.32; 95% confidence interval, 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR, 0.28; 95% CI, 0.10-0.79).
The 4-year Kaplan-Meier primary event rates were similar in both racial/ethnic minority and nonminority groups that received catheter ablation (12.3% vs. 9.9%).
However, the 4-year event rate was much higher among nonminority participants than among racial and ethnic minorities who received drug therapy (27.4% vs. 9.4%).
The corresponding all-cause 4-year mortality rates were 8.1% and 6.7%, respectively, in the ablation arm and 20.2% and 4.5%, respectively, in the drug arm.
Dr. Thomas and colleagues point out that heart failure in racial and ethnic minorities, particularly Black patients, is typically due to hypertensive heart disease, whereas in non-Hispanic White patients, it is overwhelmingly associated with coronary artery disease. “Our results in CABANA, therefore, raise the possibility that the variations in the prevalence of the heart diseases associated with AFib might account for differences in the benefits observed with ablation therapy.”
Prior data suggest that AFib in the setting of heart failure with either reduced or preserved ejection fraction has substantially better clinical outcomes with ablation versus drug therapy, but most studies either do not report racial/ethnic demographics or enroll very low numbers of minorities, they note.
Andrea M. Russo, MD, a professor of medicine at Rowan University, Camden, New Jersey, asks why drug therapy might result in worse outcomes in racial and ethnic minorities in an accompanying editorial.
“Those who received ablation did better than those who received drugs, and the main reason for that is not that ablation works better in minorities than nonminorities, it’s because drugs are worse in minority patients than they are in nonminority patients. This means that either the way we are using the drugs or the ones that we are using in minority patients are resulting in worse overall outcomes,” Dr. Russo told this news organization.
“The minority patients were younger and yet had more hypertension at baseline. There could be all kinds of factors contributing to their health,” she said.
Dr. Russo agrees with Dr. Thomas on the need to enroll diverse populations in clinical trials.
“Dr. Thomas should be commended. He did a fabulous job of looking at this issue. It’s only 10% of the group, but it is better than what we have had so far, and this is a start,” Dr. Russo said. “It’s bringing recognition to how important it is to make sure that we include underrepresented populations in these trials and also that we offer all appropriate therapies to everyone.”
Dr. Thomas reports financial relationships with Janssen, Pfizer, Biosense Webster. Dr. Russo reports no relevant financial relationships. The study was funded by the National Institutes of Health, St. Jude Medical Foundation and Corporation, Biosense Webster, Medtronic, and Boston Scientific.
A version of this article first appeared on Medscape.com.
Prophylactic anticoagulation tied to lower death rate in COVID
Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.
In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.
And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.
The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.
“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.
“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.
Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.
“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”
They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”
Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.
The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.
“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.
“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”
Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.
Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.
The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.
Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.
In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.
Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).
Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.
However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
Study boosts confidence
Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.
“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.
“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.
The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.
In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.
And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.
The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.
“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.
“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.
Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.
“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”
They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”
Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.
The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.
“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.
“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”
Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.
Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.
The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.
Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.
In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.
Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).
Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.
However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
Study boosts confidence
Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.
“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.
“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.
The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Prophylactic anticoagulation to prevent venous thromboembolism (VTE) was associated with reduced 60-day mortality in patients with COVID-19 who were ill enough to require hospitalization, a new report shows.
In a cohort study of more than 1,300 hospitalized patients with COVID-19 infection across 30 hospitals in Michigan, both prophylactic- and therapeutic-dose anticoagulation were associated with reduced in-hospital mortality; however, at 60 days, only prophylactic-dose anticoagulation remained associated with lower mortality.
And adherence was key; nonadherence, or missing 2 days or more of anticoagulation, was linked to more deaths at 60 days.
The findings, which were published online June 11 in JAMA Network Open, are final proof that a prophylactic anticoagulation strategy for the hospitalized COVID population is, indeed, the right one, Valerie M. Vaughn, MD, director of hospital medicine research at the University of Utah, Salt Lake City, said in an interview.
“We’ve probably always known that patients with COVID need prophylaxis for VTE, but we found that early on, unfortunately, that wasn’t being done,” Dr. Vaughn said.
“Now, we see that prophylactic rates have increased. We always knew to use anticoagulation prophylactically in patients who were hospitalized with infection because of their risk for VTE, so this study just drives home that proper adherence to an anticoagulation protocol improves mortality,” she said.
Dr. Vaughn was on the front lines when COVID-19 came to Michigan, where the research was conducted.
“We probably should have been anticoagulating from the get-go, but you have to remember that in the early days of COVID, the hospitals in Michigan were being overwhelmed. They didn’t have PPE. They were taking care of patients outside of their typical hospital beds or setting up field hospitals,” she said. “It was not quite as bad as New York, but at the University of Michigan, we set up four or five ICUs outside of our normal care.”
They also converted the top floor of their pediatric hospital into an ICU to take care of patients with COVID during the first surge, she added. “We didn’t know much about this disease, but faced with this influx of patients, many of whom were dying with blood clots, we had to do something.”
Some hospitals began prophylactically anticoagulating their patients, but others hesitated before adopting the strategy. “But now we feel confident that prophylactic anticoagulation, done according to the right protocol, with no interruptions in the treatment, is beneficial,” Dr. Vaughn said.
The best medication choice is enoxaparin (Lovenox), which can be given once a day, as opposed to heparin, which needs to be given via injection three times a day, she said.
“Prophylactic dose anticoagulation is typically given by an injection under the skin, but a lot of times, I’ve had patients tell me they feel like a human pin cushion and have all these bruises from being stuck with needles every day, which I can totally relate to,” she said.
“It is important for us as clinicians to explain that we’re having to poke our patients because it is good for them and will help them fight COVID,” she added. “Also having the once-a-day option is going to be a lot better for adherence, and adherence to the protocol, not missing any days, is key to the better outcome.”
Dr. Vaughn and her team reviewed the charts of 1,351 patients (48% women, 49% Black, median age 64 [range 52-75]) who were hospitalized throughout Michigan during the first several months of the COVID-19 pandemic, from March to June 2020.
Only 18 patients (1.3%) had a confirmed VTE and 219 patients (16.2%) received treatment-dose anticoagulation.
The researchers noted that use of treatment-dose anticoagulation without imaging ranged from 0% to 29% across hospitals and increased significantly over time.
Of the 1,127 patients who received anticoagulation, 392 (34.8%) missed 2 days or more of prophylaxis.
In addition, there were varying rates of missed prophylaxis among the hospitals, from 11% to 61%, but these rates decreased markedly over time.
Missed doses were associated with a higher 60-day mortality (adjusted hazard ratio, 1.31; 95% confidence interval, 1.03-1.67), but not in-hospital mortality (aHR, 0.97; 95% CI, 0.91-1.03).
Compared with no anticoagulation, receiving any dose of anticoagulation was associated with lower in-hospital mortality.
However, only prophylactic-dose anticoagulation remained associated with lower mortality at 60 days. The adjusted hazard ratio for prophylactic-dose anticoagulation was 0.71 (95% CI, 0.51-0.90), compared with 0.92 (95% CI, 0.63-1.35) for treatment-dose anticoagulation.
Study boosts confidence
Despite its limitations, the study should make clinicians more confident that the use of prophylactic anticoagulation is warranted for hospitalized patients with COVID-19, write Andrew B. Dicks, MD, and Ido Weinberg, MD, from Massachusetts General Hospital, Boston, in an invited commentary.
“Practically, we still lack the granular data we need to help guide us in patient-by-patient decision-making – such as anticoagulation agent choice, dosage, and duration of therapy – especially as dictated by acuity of patient illness,” Dr. Dicks and Dr. Weinberg note.
“While we still await the data from randomized controlled trials to guide the optimal anticoagulation dose and duration, this study adds significant merit to the previously published recommendations from several different medical organizations regarding the use of prophylactic anticoagulation in hospitalized patients with COVID-19,” Dr. Dicks told this news organization.
The study was supported by Blue Cross and Blue Shield of Michigan and Blue Care Network as part of their Value Partnerships program. Dr. Vaughn has reported receiving speaking fees from Thermo Fisher Scientific. Dr. Dicks and Dr. Weinberg have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Remarkable’ response to diabetes drug in resistant bipolar depression
Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.
In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.
“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.
“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.
The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
Chronic inflammation
The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.
Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.
“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.
Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.
“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.
The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.
All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.
All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.
Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.
Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
Highly resistant population
The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.
By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.
“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.
Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.
“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.
“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”
“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
A holistic approach
Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.
“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.
The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.
In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.
“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.
“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.
The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
Chronic inflammation
The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.
Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.
“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.
Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.
“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.
The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.
All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.
All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.
Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.
Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
Highly resistant population
The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.
By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.
“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.
Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.
“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.
“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”
“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
A holistic approach
Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.
“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.
The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.
In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.
“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.
“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.
The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
Chronic inflammation
The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.
Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.
“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.
Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.
“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.
The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.
All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.
All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.
Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.
Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
Highly resistant population
The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.
By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.
“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.
Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.
“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.
“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”
“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
A holistic approach
Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.
“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.
The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Once-weekly oral antipsychotic for schizophrenia on the horizon
A novel, ultra–long-acting oral formulation of the antipsychotic risperidone (Risperdal) only needs to be taken once weekly and appears to be safe and effective, results of a new phase 2 study suggest.
The new formulation, LYN-005 (Lyndra Therapeutics), quickly reached therapeutic levels in patients, provided sustained exposure to risperidone active moiety over 7 days, and reduced peak drug exposure.
“This novel formulation has the potential to improve treatment adherence and quality of life in patients with schizophrenia or schizoaffective disorder,” study investigator David Walling, PhD, chief clinical officer for the Collaborative NeuroScience Network, Long Beach, Calif., said in an interview.
The findings were presented at the 2021 American Society of Clinical Psychopharmacology annual meeting.
Adherence is key
About 50% of patients don’t take medications as prescribed, creating a significant relapse risk, Dr. Walling noted.
“Here we have the possibility of having a once-weekly oral medication, which means patients don’t have to struggle with the issue of taking the medication daily. Right now, all we have on the market for long-acting medications for schizophrenia are injectables, where the patient has to go get a shot every month or every 2 weeks in order to have the medication in their system for a longer period of time,” he added.
The study included 32 clinically stable patients with a primary diagnosis of schizophrenia or schizoaffective disorder.
Patients received immediate-release (IR) risperidone at 2 mg or 4 mg, based on their current antipsychotic dose, for 13 days.
They were then randomly assigned 3:1 to receive either IR risperidone-matched placebo and LYN-005 at 14 mg or 28 mg risperidone (12 patients per group), or to LYN-005 matched placebo and IR risperidone, 2 mg or 4 mg, (4 patients per group) for 3 weeks.
LYN-05 was administered once weekly for a total of three doses. IR risperidone was administered once daily.
The study’s primary endpoints were pharmacokinetics after LYN-005 and IR risperidone and the incidence of adverse events.
Following LYN-005 administration, systemic exposure to risperidone active moiety (risperidone and 9-hydroxyrisperidone combined) increased with the increasing dose. Peak concentration occurred within the first 3 days of dosing and peak exposures from LYN-005 were lower than with IR risperidone.
“Steady state was achieved around day 15. It didn’t take 3 weeks of dosing for patients to achieve steady state. We achieved that around day 15,” Dr. Walling said.
LYN-005 was well tolerated in the 85% of study participants who received all three doses.
Adverse events occurred in 18 (75%) patients who received LYN-005. Of these, 10 were with the 14-mg dose, and 8 with the 28-mg dose.
The most common AEs were gastrointestinal, which occurred in 13 (54%) patients receiving LYN-005, with a higher incidence in the 28-mg group than in the 14 mg group.
Additionally, nine patients had abdominal pain, discomfort, or tenderness, and five patients (21%) had nausea.
Overall, the incidence of adverse events was higher for LYN-005, compared with IR risperidone, but they were judged to be mild and transitory, with fewer AEs reported with subsequent LYN-005 dosing. After the first dose, 58% of patients reported an AE; this dropped to 18% after the third dose.
An important development
Commenting on the findings, Ira D. Glick, MD, professor emeritus, Stanford (Calif.) University, said: “The major problem with schizophrenia is getting adherence.”
“The better the adherence, the better the outcome, the worst the adherence, the worse the outcome, so being able to take a preparation less often is a very important advance in the field,” said Dr. Glick, who was not involved in the research
Long-acting preparations for chronic mental illness represent a significant advance, he said.
“The future of the treatment of schizophrenia is long-acting injectables. That is the trend,” Dr. Glick explained. “The oral once-a-week preparation may be useful in a group of patients who are phobic about needles, but with the injections, you can be sure that the patient has received their medication. With the oral, there is more of a chance to be noncompliant.
“That said, having an effective, longer-acting oral for those who refuse injections is helpful. to ensure adherence to treatment. We know treatment works, we know it is going to save lives, and that’s what this ultra–long-acting formulation is promoting.”
Dr. Glick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel, ultra–long-acting oral formulation of the antipsychotic risperidone (Risperdal) only needs to be taken once weekly and appears to be safe and effective, results of a new phase 2 study suggest.
The new formulation, LYN-005 (Lyndra Therapeutics), quickly reached therapeutic levels in patients, provided sustained exposure to risperidone active moiety over 7 days, and reduced peak drug exposure.
“This novel formulation has the potential to improve treatment adherence and quality of life in patients with schizophrenia or schizoaffective disorder,” study investigator David Walling, PhD, chief clinical officer for the Collaborative NeuroScience Network, Long Beach, Calif., said in an interview.
The findings were presented at the 2021 American Society of Clinical Psychopharmacology annual meeting.
Adherence is key
About 50% of patients don’t take medications as prescribed, creating a significant relapse risk, Dr. Walling noted.
“Here we have the possibility of having a once-weekly oral medication, which means patients don’t have to struggle with the issue of taking the medication daily. Right now, all we have on the market for long-acting medications for schizophrenia are injectables, where the patient has to go get a shot every month or every 2 weeks in order to have the medication in their system for a longer period of time,” he added.
The study included 32 clinically stable patients with a primary diagnosis of schizophrenia or schizoaffective disorder.
Patients received immediate-release (IR) risperidone at 2 mg or 4 mg, based on their current antipsychotic dose, for 13 days.
They were then randomly assigned 3:1 to receive either IR risperidone-matched placebo and LYN-005 at 14 mg or 28 mg risperidone (12 patients per group), or to LYN-005 matched placebo and IR risperidone, 2 mg or 4 mg, (4 patients per group) for 3 weeks.
LYN-05 was administered once weekly for a total of three doses. IR risperidone was administered once daily.
The study’s primary endpoints were pharmacokinetics after LYN-005 and IR risperidone and the incidence of adverse events.
Following LYN-005 administration, systemic exposure to risperidone active moiety (risperidone and 9-hydroxyrisperidone combined) increased with the increasing dose. Peak concentration occurred within the first 3 days of dosing and peak exposures from LYN-005 were lower than with IR risperidone.
“Steady state was achieved around day 15. It didn’t take 3 weeks of dosing for patients to achieve steady state. We achieved that around day 15,” Dr. Walling said.
LYN-005 was well tolerated in the 85% of study participants who received all three doses.
Adverse events occurred in 18 (75%) patients who received LYN-005. Of these, 10 were with the 14-mg dose, and 8 with the 28-mg dose.
The most common AEs were gastrointestinal, which occurred in 13 (54%) patients receiving LYN-005, with a higher incidence in the 28-mg group than in the 14 mg group.
Additionally, nine patients had abdominal pain, discomfort, or tenderness, and five patients (21%) had nausea.
Overall, the incidence of adverse events was higher for LYN-005, compared with IR risperidone, but they were judged to be mild and transitory, with fewer AEs reported with subsequent LYN-005 dosing. After the first dose, 58% of patients reported an AE; this dropped to 18% after the third dose.
An important development
Commenting on the findings, Ira D. Glick, MD, professor emeritus, Stanford (Calif.) University, said: “The major problem with schizophrenia is getting adherence.”
“The better the adherence, the better the outcome, the worst the adherence, the worse the outcome, so being able to take a preparation less often is a very important advance in the field,” said Dr. Glick, who was not involved in the research
Long-acting preparations for chronic mental illness represent a significant advance, he said.
“The future of the treatment of schizophrenia is long-acting injectables. That is the trend,” Dr. Glick explained. “The oral once-a-week preparation may be useful in a group of patients who are phobic about needles, but with the injections, you can be sure that the patient has received their medication. With the oral, there is more of a chance to be noncompliant.
“That said, having an effective, longer-acting oral for those who refuse injections is helpful. to ensure adherence to treatment. We know treatment works, we know it is going to save lives, and that’s what this ultra–long-acting formulation is promoting.”
Dr. Glick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A novel, ultra–long-acting oral formulation of the antipsychotic risperidone (Risperdal) only needs to be taken once weekly and appears to be safe and effective, results of a new phase 2 study suggest.
The new formulation, LYN-005 (Lyndra Therapeutics), quickly reached therapeutic levels in patients, provided sustained exposure to risperidone active moiety over 7 days, and reduced peak drug exposure.
“This novel formulation has the potential to improve treatment adherence and quality of life in patients with schizophrenia or schizoaffective disorder,” study investigator David Walling, PhD, chief clinical officer for the Collaborative NeuroScience Network, Long Beach, Calif., said in an interview.
The findings were presented at the 2021 American Society of Clinical Psychopharmacology annual meeting.
Adherence is key
About 50% of patients don’t take medications as prescribed, creating a significant relapse risk, Dr. Walling noted.
“Here we have the possibility of having a once-weekly oral medication, which means patients don’t have to struggle with the issue of taking the medication daily. Right now, all we have on the market for long-acting medications for schizophrenia are injectables, where the patient has to go get a shot every month or every 2 weeks in order to have the medication in their system for a longer period of time,” he added.
The study included 32 clinically stable patients with a primary diagnosis of schizophrenia or schizoaffective disorder.
Patients received immediate-release (IR) risperidone at 2 mg or 4 mg, based on their current antipsychotic dose, for 13 days.
They were then randomly assigned 3:1 to receive either IR risperidone-matched placebo and LYN-005 at 14 mg or 28 mg risperidone (12 patients per group), or to LYN-005 matched placebo and IR risperidone, 2 mg or 4 mg, (4 patients per group) for 3 weeks.
LYN-05 was administered once weekly for a total of three doses. IR risperidone was administered once daily.
The study’s primary endpoints were pharmacokinetics after LYN-005 and IR risperidone and the incidence of adverse events.
Following LYN-005 administration, systemic exposure to risperidone active moiety (risperidone and 9-hydroxyrisperidone combined) increased with the increasing dose. Peak concentration occurred within the first 3 days of dosing and peak exposures from LYN-005 were lower than with IR risperidone.
“Steady state was achieved around day 15. It didn’t take 3 weeks of dosing for patients to achieve steady state. We achieved that around day 15,” Dr. Walling said.
LYN-005 was well tolerated in the 85% of study participants who received all three doses.
Adverse events occurred in 18 (75%) patients who received LYN-005. Of these, 10 were with the 14-mg dose, and 8 with the 28-mg dose.
The most common AEs were gastrointestinal, which occurred in 13 (54%) patients receiving LYN-005, with a higher incidence in the 28-mg group than in the 14 mg group.
Additionally, nine patients had abdominal pain, discomfort, or tenderness, and five patients (21%) had nausea.
Overall, the incidence of adverse events was higher for LYN-005, compared with IR risperidone, but they were judged to be mild and transitory, with fewer AEs reported with subsequent LYN-005 dosing. After the first dose, 58% of patients reported an AE; this dropped to 18% after the third dose.
An important development
Commenting on the findings, Ira D. Glick, MD, professor emeritus, Stanford (Calif.) University, said: “The major problem with schizophrenia is getting adherence.”
“The better the adherence, the better the outcome, the worst the adherence, the worse the outcome, so being able to take a preparation less often is a very important advance in the field,” said Dr. Glick, who was not involved in the research
Long-acting preparations for chronic mental illness represent a significant advance, he said.
“The future of the treatment of schizophrenia is long-acting injectables. That is the trend,” Dr. Glick explained. “The oral once-a-week preparation may be useful in a group of patients who are phobic about needles, but with the injections, you can be sure that the patient has received their medication. With the oral, there is more of a chance to be noncompliant.
“That said, having an effective, longer-acting oral for those who refuse injections is helpful. to ensure adherence to treatment. We know treatment works, we know it is going to save lives, and that’s what this ultra–long-acting formulation is promoting.”
Dr. Glick has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
NCAA athletes: ECG abnormalities persist after COVID-19
College athletes who have recently recovered from COVID-19 infection show cardiac abnormalities on electrocardiography.
In a small study of ECGs on National Collegiate Athletic Association Division II athletes, those who had been infected with COVID-19 had a prolonged PR interval, compared with matched athletes who had not been infected.
The study was presented at the 2021 Virtual American College of Sports Medicine Annual Meeting & World Congresses.
“The NCAA was requiring athletes to have an ECG for return to play after noting there could be some myocardial abnormalities following COVID-19 infection,” lead author Frank Wyatt, EdD, a sports physiologist and professor at Midwestern State University in Wichita Falls, Tex., told this news organization.
“Our head athletic trainer asked me if I could do ECGs on our COVID-19–recovered athletes, and I decided to do a matched pair–design study to see how our infected and noninfected athletes compared,” Dr. Wyatt said.
Research in the general population has suggested that COVID-19 can cause damage not only to the lungs, but also to the myocardium, he said. “Recent literature suggests COVID-19 is actually infusing itself into the cells of the myocardium and killing those cells, much the way it did in the lung, and possibly kidney and liver, so it’s going after those organs as well, not just the lungs.”
Dr. Wyatt presented results of ECGs that were done in seven COVID-infected athletes and in seven controls, who were free of infection.
The athletes’ recovery from COVID-19 infection was documented after two negative tests.
All subjects were matched by sport, gender, ethnicity, and anthropometry. Investigators obtained ECG recordings 2-4 weeks after the infected athletes had their recovery documented.
Study participants engaged in football, basketball, soccer, and volleyball, and Dr. Wyatt and associates were blinded as to their infected or control status.
Participants self-reported their ethnicity. Most were White or African American.
The main abnormality found was a prolonged PR interval. In the athletes who were recovered from COVID-19, the mean PR interval was 183.6 milliseconds (± 32.4 ms), compared with 141.7 ms (± 22.7 ms) among the controls.
Baseline ECGs for all young athletes?
Dr. Wyatt said he would like to see ECGs done at baseline as part of the physical exam NCAA athletes have to undergo at the start of each season. But that would be expensive.
“It has been suggested that they all need to have ECGs for baseline information, but they don’t do it because of money. If we had that baseline data on these athletes it would really give us a better picture of whether there was damage or not,” he said. “At our small university, if I wasn’t available to do these ECGs, our athletic department would then have to go to the cardiologist to do them, and that is tremendously expensive. It has also been suggested that high school athletes get ECGs as a preliminary test when they start their season, and I think that is warranted as well as for the NCAA athletes, but because of the expense, they’re not doing it.”
Dr. Wyatt has continued to do ECGs on athletes who have survived COVID-19 and to date has ECG data on 70 athletes. He plans further comparisons between the infected and noninfected athletes.
“We want to see if we can solidify the results we presented at ACSM. We had small numbers, so our follow up is to see if we can statistically show in a more robust manner whether or not there was widespread abnormality in the athletes who got infected. They were only 2-4 weeks post infected, and I don’t know what the long-term effects are going to be,” he said.
May be an important finding
“This may be an important finding, but needs many more athletes, as there were only seven in each group,” commented Curt J. Daniels, MD, director of the sports cardiology program and professor at Ohio State University Wexner Medical Center, Columbus.
“Plus, it will need some imaging correlate and recovery ECGs to see if this effect of PR interval prolongation correlates with myocardial changes and whether it persists or resolves,” added Dr. Daniels, who was not part of the study. “But I do find this interesting. ... I agree we are looking for any ECG sign that might help tell us who needs a cardiac MRI. The Big Ten COVID-19 Cardiac Registry has 1,597 ECGs on post COVID athletes we are analyzing, but preliminarily did not see any changes.”
Dr. Wyatt and Dr. Daniels reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
College athletes who have recently recovered from COVID-19 infection show cardiac abnormalities on electrocardiography.
In a small study of ECGs on National Collegiate Athletic Association Division II athletes, those who had been infected with COVID-19 had a prolonged PR interval, compared with matched athletes who had not been infected.
The study was presented at the 2021 Virtual American College of Sports Medicine Annual Meeting & World Congresses.
“The NCAA was requiring athletes to have an ECG for return to play after noting there could be some myocardial abnormalities following COVID-19 infection,” lead author Frank Wyatt, EdD, a sports physiologist and professor at Midwestern State University in Wichita Falls, Tex., told this news organization.
“Our head athletic trainer asked me if I could do ECGs on our COVID-19–recovered athletes, and I decided to do a matched pair–design study to see how our infected and noninfected athletes compared,” Dr. Wyatt said.
Research in the general population has suggested that COVID-19 can cause damage not only to the lungs, but also to the myocardium, he said. “Recent literature suggests COVID-19 is actually infusing itself into the cells of the myocardium and killing those cells, much the way it did in the lung, and possibly kidney and liver, so it’s going after those organs as well, not just the lungs.”
Dr. Wyatt presented results of ECGs that were done in seven COVID-infected athletes and in seven controls, who were free of infection.
The athletes’ recovery from COVID-19 infection was documented after two negative tests.
All subjects were matched by sport, gender, ethnicity, and anthropometry. Investigators obtained ECG recordings 2-4 weeks after the infected athletes had their recovery documented.
Study participants engaged in football, basketball, soccer, and volleyball, and Dr. Wyatt and associates were blinded as to their infected or control status.
Participants self-reported their ethnicity. Most were White or African American.
The main abnormality found was a prolonged PR interval. In the athletes who were recovered from COVID-19, the mean PR interval was 183.6 milliseconds (± 32.4 ms), compared with 141.7 ms (± 22.7 ms) among the controls.
Baseline ECGs for all young athletes?
Dr. Wyatt said he would like to see ECGs done at baseline as part of the physical exam NCAA athletes have to undergo at the start of each season. But that would be expensive.
“It has been suggested that they all need to have ECGs for baseline information, but they don’t do it because of money. If we had that baseline data on these athletes it would really give us a better picture of whether there was damage or not,” he said. “At our small university, if I wasn’t available to do these ECGs, our athletic department would then have to go to the cardiologist to do them, and that is tremendously expensive. It has also been suggested that high school athletes get ECGs as a preliminary test when they start their season, and I think that is warranted as well as for the NCAA athletes, but because of the expense, they’re not doing it.”
Dr. Wyatt has continued to do ECGs on athletes who have survived COVID-19 and to date has ECG data on 70 athletes. He plans further comparisons between the infected and noninfected athletes.
“We want to see if we can solidify the results we presented at ACSM. We had small numbers, so our follow up is to see if we can statistically show in a more robust manner whether or not there was widespread abnormality in the athletes who got infected. They were only 2-4 weeks post infected, and I don’t know what the long-term effects are going to be,” he said.
May be an important finding
“This may be an important finding, but needs many more athletes, as there were only seven in each group,” commented Curt J. Daniels, MD, director of the sports cardiology program and professor at Ohio State University Wexner Medical Center, Columbus.
“Plus, it will need some imaging correlate and recovery ECGs to see if this effect of PR interval prolongation correlates with myocardial changes and whether it persists or resolves,” added Dr. Daniels, who was not part of the study. “But I do find this interesting. ... I agree we are looking for any ECG sign that might help tell us who needs a cardiac MRI. The Big Ten COVID-19 Cardiac Registry has 1,597 ECGs on post COVID athletes we are analyzing, but preliminarily did not see any changes.”
Dr. Wyatt and Dr. Daniels reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
College athletes who have recently recovered from COVID-19 infection show cardiac abnormalities on electrocardiography.
In a small study of ECGs on National Collegiate Athletic Association Division II athletes, those who had been infected with COVID-19 had a prolonged PR interval, compared with matched athletes who had not been infected.
The study was presented at the 2021 Virtual American College of Sports Medicine Annual Meeting & World Congresses.
“The NCAA was requiring athletes to have an ECG for return to play after noting there could be some myocardial abnormalities following COVID-19 infection,” lead author Frank Wyatt, EdD, a sports physiologist and professor at Midwestern State University in Wichita Falls, Tex., told this news organization.
“Our head athletic trainer asked me if I could do ECGs on our COVID-19–recovered athletes, and I decided to do a matched pair–design study to see how our infected and noninfected athletes compared,” Dr. Wyatt said.
Research in the general population has suggested that COVID-19 can cause damage not only to the lungs, but also to the myocardium, he said. “Recent literature suggests COVID-19 is actually infusing itself into the cells of the myocardium and killing those cells, much the way it did in the lung, and possibly kidney and liver, so it’s going after those organs as well, not just the lungs.”
Dr. Wyatt presented results of ECGs that were done in seven COVID-infected athletes and in seven controls, who were free of infection.
The athletes’ recovery from COVID-19 infection was documented after two negative tests.
All subjects were matched by sport, gender, ethnicity, and anthropometry. Investigators obtained ECG recordings 2-4 weeks after the infected athletes had their recovery documented.
Study participants engaged in football, basketball, soccer, and volleyball, and Dr. Wyatt and associates were blinded as to their infected or control status.
Participants self-reported their ethnicity. Most were White or African American.
The main abnormality found was a prolonged PR interval. In the athletes who were recovered from COVID-19, the mean PR interval was 183.6 milliseconds (± 32.4 ms), compared with 141.7 ms (± 22.7 ms) among the controls.
Baseline ECGs for all young athletes?
Dr. Wyatt said he would like to see ECGs done at baseline as part of the physical exam NCAA athletes have to undergo at the start of each season. But that would be expensive.
“It has been suggested that they all need to have ECGs for baseline information, but they don’t do it because of money. If we had that baseline data on these athletes it would really give us a better picture of whether there was damage or not,” he said. “At our small university, if I wasn’t available to do these ECGs, our athletic department would then have to go to the cardiologist to do them, and that is tremendously expensive. It has also been suggested that high school athletes get ECGs as a preliminary test when they start their season, and I think that is warranted as well as for the NCAA athletes, but because of the expense, they’re not doing it.”
Dr. Wyatt has continued to do ECGs on athletes who have survived COVID-19 and to date has ECG data on 70 athletes. He plans further comparisons between the infected and noninfected athletes.
“We want to see if we can solidify the results we presented at ACSM. We had small numbers, so our follow up is to see if we can statistically show in a more robust manner whether or not there was widespread abnormality in the athletes who got infected. They were only 2-4 weeks post infected, and I don’t know what the long-term effects are going to be,” he said.
May be an important finding
“This may be an important finding, but needs many more athletes, as there were only seven in each group,” commented Curt J. Daniels, MD, director of the sports cardiology program and professor at Ohio State University Wexner Medical Center, Columbus.
“Plus, it will need some imaging correlate and recovery ECGs to see if this effect of PR interval prolongation correlates with myocardial changes and whether it persists or resolves,” added Dr. Daniels, who was not part of the study. “But I do find this interesting. ... I agree we are looking for any ECG sign that might help tell us who needs a cardiac MRI. The Big Ten COVID-19 Cardiac Registry has 1,597 ECGs on post COVID athletes we are analyzing, but preliminarily did not see any changes.”
Dr. Wyatt and Dr. Daniels reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.