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New European guidelines ‘drastically’ reduce statin eligibility
New risk thresholds used to guide statin therapy for primary prevention of atherosclerotic cardiovascular disease in the latest European guidelines dramatically reduce eligibility for statin use in low-risk countries, a new study has found.
The authors reported that and essentially eliminate a statin indication in women.
“We have guidelines in place to try to prevent cardiovascular disease but the risk threshold in this new guideline means that almost nobody qualifies for treatment in many countries, which will lead to almost no prevention of future cardiovascular disease in those countries,” lead author Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, commented in an interview.
“We argue that the risk thresholds need to be lowered to get the statin eligibility in European countries to be in line with thresholds in the U.K. and U.S., which are based on randomized, controlled trials,” he added.
The study was published online in JAMA Cardiology.
An accompanying editorial describes the results of the study as “alarming,” and, if confirmed, said the guidelines should be revisited to “prevent a step backwards in the use of statins in primary prevention.”
For the study, Dr. Mortensen and colleagues set out to compare the clinical performance of the new European prevention guidelines with American College of Cardiology/American Heart Association, United Kingdom–National Institute for Health and Care Excellence, and the 2019 European guidelines in a contemporary European cohort of 66,909 apparently healthy individuals from the Copenhagen General Population Study.
During the 9-year follow-up, a range of 2,962-4,277 nonfatal and fatal cardiovascular events was observed, as defined by the models in the various guidelines.
Results showed that although the new 2021 European guidelines introduced a new and improved risk model, known as SCORE2, the updated age-specific recommendations dramatically reduced eligibility for a class I recommendation for statin therapy to only 4% of individuals, aged 40-69 years, and less than 1% of women.
This is in sharp contrast to the previous 2019 European guidelines as well as current UK-NICE and US-ACC/AHA guidelines that provide class I/strong recommendations to 20%, 26%, and 34% of individuals, respectively, with better clinical performance in both men and women, the authors report.
The researchers also reported other analyses in which the sensitivity of the new European guidelines was improved considerably by lowering the treatment thresholds.
Dr. Mortensen explained to this news organization that the original SCORE risk model used in ESC guidelines was problematic as it only predicts the 10-year risk of fatal atherosclerotic cardiovascular events, whereas those from the United States and United Kingdom used both fatal and nonfatal cardiovascular events.
“Now the ESC has updated its model and the new model is much better in that it predicts both fatal and nonfatal events, and the predicted risk correlates well with the actual risk. So that’s a big step forward. However, the new thresholds for statin treatment are far too high for low-risk European countries because very few individuals will now qualify for statin therapy,” he said.
“The problem is that, if we use these guidelines, the vast majority of those individuals who will develop cardiovascular disease within 10 years will not be assigned statin therapy that can reduce this risk. There will be lots of individuals who are at high risk of cardiovascular disease, but these guidelines will not identify them as needing to take a statin,” Dr. Mortensen commented.
“If we use the U.K. or U.S. guidelines, far more people in these low-risk European countries would be eligible for statin therapy and we would prevent far more events than if we use the new ESC guidelines,” he added.
Dr. Mortensen explained that the problem arises from having four different risk score models in Europe for areas at different risk, but they all use the same risk thresholds for statin treatment.
“In general, Eastern European countries have higher risk than Western European countries, so these guidelines may work quite well in Eastern European countries but in low-risk Western European countries, where the low-risk score model is used, very few people will qualify for statin therapy,” he said.
While Dr. Mortensen is not against the idea of different risk models in areas that have different risks, he says this needs to be accompanied by different risk thresholds in the different risk areas.
Asked whether there is an argument that most individuals in low-risk countries may not need to take a statin, Dr. Mortensen countered: “One of the reasons the risk is low in many of these European countries is the high use of preventative medication. So, if a threshold that is too high is used most people will not take a statin anymore and the risk in these countries will increase again.”
Authors of the accompanying editorial, Ann Marie Navar, MD, PhD, University of Texas Southwestern Medical Center, Dallas; Gregg C. Fonarow, MD, University of California, Los Angeles; and Michael J. Pencina, PhD, Duke University Medical Center, Durham, N.C., agreed with Dr. Mortensen that the problems appear to arise from use of a risk score that is highly influenced by regional cardiovascular burden.
They point out that under the current guidelines, a 55-year-old woman (smoker; systolic blood pressure, 130 mm Hg; non–HDL cholesterol, 4.0 mmol/L) would have a 10-year predicted risk of having a cardiovascular event of 5% in Denmark but a predicted risk of 18% in Romania.
“While there may be regional differences in environmental risk factors, location alone should not cause a fourfold difference in an individual’s predicted cardiovascular risk,” they wrote.
The editorialists also elaborated on Dr. Mortensen’s point that the new guideline creates a system that eventually becomes a victim of its own success.
“As countries are successful in implementing statin therapy to lower CVD, CVD rates drop, and progressively fewer individuals are then eligible for the very therapy that contributed to the decline in CVD in the first place,” they noted.
The editorialists called for the analysis to be replicated in other low-risk countries and extended to higher-risk regions, with a focus on potential overtreatment of men and older adults.
“If confirmed, the present findings should be a catalyst for the ESC to revisit or augment their current guidelines to prevent a step backward in the use of statins in primary prevention,” they concluded.
This news organization asked the ESC for a response to the findings, but did not comment by press time.
This work was supported by the Lundbeck Foundation, Herlev and Gentofte Hospital, Copenhagen University Hospital, the Copenhagen County Foundation, and Aarhus University, Denmark. Dr. Mortensen reported no disclosures.
A version of this article first appeared on Medscape.com.
New risk thresholds used to guide statin therapy for primary prevention of atherosclerotic cardiovascular disease in the latest European guidelines dramatically reduce eligibility for statin use in low-risk countries, a new study has found.
The authors reported that and essentially eliminate a statin indication in women.
“We have guidelines in place to try to prevent cardiovascular disease but the risk threshold in this new guideline means that almost nobody qualifies for treatment in many countries, which will lead to almost no prevention of future cardiovascular disease in those countries,” lead author Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, commented in an interview.
“We argue that the risk thresholds need to be lowered to get the statin eligibility in European countries to be in line with thresholds in the U.K. and U.S., which are based on randomized, controlled trials,” he added.
The study was published online in JAMA Cardiology.
An accompanying editorial describes the results of the study as “alarming,” and, if confirmed, said the guidelines should be revisited to “prevent a step backwards in the use of statins in primary prevention.”
For the study, Dr. Mortensen and colleagues set out to compare the clinical performance of the new European prevention guidelines with American College of Cardiology/American Heart Association, United Kingdom–National Institute for Health and Care Excellence, and the 2019 European guidelines in a contemporary European cohort of 66,909 apparently healthy individuals from the Copenhagen General Population Study.
During the 9-year follow-up, a range of 2,962-4,277 nonfatal and fatal cardiovascular events was observed, as defined by the models in the various guidelines.
Results showed that although the new 2021 European guidelines introduced a new and improved risk model, known as SCORE2, the updated age-specific recommendations dramatically reduced eligibility for a class I recommendation for statin therapy to only 4% of individuals, aged 40-69 years, and less than 1% of women.
This is in sharp contrast to the previous 2019 European guidelines as well as current UK-NICE and US-ACC/AHA guidelines that provide class I/strong recommendations to 20%, 26%, and 34% of individuals, respectively, with better clinical performance in both men and women, the authors report.
The researchers also reported other analyses in which the sensitivity of the new European guidelines was improved considerably by lowering the treatment thresholds.
Dr. Mortensen explained to this news organization that the original SCORE risk model used in ESC guidelines was problematic as it only predicts the 10-year risk of fatal atherosclerotic cardiovascular events, whereas those from the United States and United Kingdom used both fatal and nonfatal cardiovascular events.
“Now the ESC has updated its model and the new model is much better in that it predicts both fatal and nonfatal events, and the predicted risk correlates well with the actual risk. So that’s a big step forward. However, the new thresholds for statin treatment are far too high for low-risk European countries because very few individuals will now qualify for statin therapy,” he said.
“The problem is that, if we use these guidelines, the vast majority of those individuals who will develop cardiovascular disease within 10 years will not be assigned statin therapy that can reduce this risk. There will be lots of individuals who are at high risk of cardiovascular disease, but these guidelines will not identify them as needing to take a statin,” Dr. Mortensen commented.
“If we use the U.K. or U.S. guidelines, far more people in these low-risk European countries would be eligible for statin therapy and we would prevent far more events than if we use the new ESC guidelines,” he added.
Dr. Mortensen explained that the problem arises from having four different risk score models in Europe for areas at different risk, but they all use the same risk thresholds for statin treatment.
“In general, Eastern European countries have higher risk than Western European countries, so these guidelines may work quite well in Eastern European countries but in low-risk Western European countries, where the low-risk score model is used, very few people will qualify for statin therapy,” he said.
While Dr. Mortensen is not against the idea of different risk models in areas that have different risks, he says this needs to be accompanied by different risk thresholds in the different risk areas.
Asked whether there is an argument that most individuals in low-risk countries may not need to take a statin, Dr. Mortensen countered: “One of the reasons the risk is low in many of these European countries is the high use of preventative medication. So, if a threshold that is too high is used most people will not take a statin anymore and the risk in these countries will increase again.”
Authors of the accompanying editorial, Ann Marie Navar, MD, PhD, University of Texas Southwestern Medical Center, Dallas; Gregg C. Fonarow, MD, University of California, Los Angeles; and Michael J. Pencina, PhD, Duke University Medical Center, Durham, N.C., agreed with Dr. Mortensen that the problems appear to arise from use of a risk score that is highly influenced by regional cardiovascular burden.
They point out that under the current guidelines, a 55-year-old woman (smoker; systolic blood pressure, 130 mm Hg; non–HDL cholesterol, 4.0 mmol/L) would have a 10-year predicted risk of having a cardiovascular event of 5% in Denmark but a predicted risk of 18% in Romania.
“While there may be regional differences in environmental risk factors, location alone should not cause a fourfold difference in an individual’s predicted cardiovascular risk,” they wrote.
The editorialists also elaborated on Dr. Mortensen’s point that the new guideline creates a system that eventually becomes a victim of its own success.
“As countries are successful in implementing statin therapy to lower CVD, CVD rates drop, and progressively fewer individuals are then eligible for the very therapy that contributed to the decline in CVD in the first place,” they noted.
The editorialists called for the analysis to be replicated in other low-risk countries and extended to higher-risk regions, with a focus on potential overtreatment of men and older adults.
“If confirmed, the present findings should be a catalyst for the ESC to revisit or augment their current guidelines to prevent a step backward in the use of statins in primary prevention,” they concluded.
This news organization asked the ESC for a response to the findings, but did not comment by press time.
This work was supported by the Lundbeck Foundation, Herlev and Gentofte Hospital, Copenhagen University Hospital, the Copenhagen County Foundation, and Aarhus University, Denmark. Dr. Mortensen reported no disclosures.
A version of this article first appeared on Medscape.com.
New risk thresholds used to guide statin therapy for primary prevention of atherosclerotic cardiovascular disease in the latest European guidelines dramatically reduce eligibility for statin use in low-risk countries, a new study has found.
The authors reported that and essentially eliminate a statin indication in women.
“We have guidelines in place to try to prevent cardiovascular disease but the risk threshold in this new guideline means that almost nobody qualifies for treatment in many countries, which will lead to almost no prevention of future cardiovascular disease in those countries,” lead author Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, commented in an interview.
“We argue that the risk thresholds need to be lowered to get the statin eligibility in European countries to be in line with thresholds in the U.K. and U.S., which are based on randomized, controlled trials,” he added.
The study was published online in JAMA Cardiology.
An accompanying editorial describes the results of the study as “alarming,” and, if confirmed, said the guidelines should be revisited to “prevent a step backwards in the use of statins in primary prevention.”
For the study, Dr. Mortensen and colleagues set out to compare the clinical performance of the new European prevention guidelines with American College of Cardiology/American Heart Association, United Kingdom–National Institute for Health and Care Excellence, and the 2019 European guidelines in a contemporary European cohort of 66,909 apparently healthy individuals from the Copenhagen General Population Study.
During the 9-year follow-up, a range of 2,962-4,277 nonfatal and fatal cardiovascular events was observed, as defined by the models in the various guidelines.
Results showed that although the new 2021 European guidelines introduced a new and improved risk model, known as SCORE2, the updated age-specific recommendations dramatically reduced eligibility for a class I recommendation for statin therapy to only 4% of individuals, aged 40-69 years, and less than 1% of women.
This is in sharp contrast to the previous 2019 European guidelines as well as current UK-NICE and US-ACC/AHA guidelines that provide class I/strong recommendations to 20%, 26%, and 34% of individuals, respectively, with better clinical performance in both men and women, the authors report.
The researchers also reported other analyses in which the sensitivity of the new European guidelines was improved considerably by lowering the treatment thresholds.
Dr. Mortensen explained to this news organization that the original SCORE risk model used in ESC guidelines was problematic as it only predicts the 10-year risk of fatal atherosclerotic cardiovascular events, whereas those from the United States and United Kingdom used both fatal and nonfatal cardiovascular events.
“Now the ESC has updated its model and the new model is much better in that it predicts both fatal and nonfatal events, and the predicted risk correlates well with the actual risk. So that’s a big step forward. However, the new thresholds for statin treatment are far too high for low-risk European countries because very few individuals will now qualify for statin therapy,” he said.
“The problem is that, if we use these guidelines, the vast majority of those individuals who will develop cardiovascular disease within 10 years will not be assigned statin therapy that can reduce this risk. There will be lots of individuals who are at high risk of cardiovascular disease, but these guidelines will not identify them as needing to take a statin,” Dr. Mortensen commented.
“If we use the U.K. or U.S. guidelines, far more people in these low-risk European countries would be eligible for statin therapy and we would prevent far more events than if we use the new ESC guidelines,” he added.
Dr. Mortensen explained that the problem arises from having four different risk score models in Europe for areas at different risk, but they all use the same risk thresholds for statin treatment.
“In general, Eastern European countries have higher risk than Western European countries, so these guidelines may work quite well in Eastern European countries but in low-risk Western European countries, where the low-risk score model is used, very few people will qualify for statin therapy,” he said.
While Dr. Mortensen is not against the idea of different risk models in areas that have different risks, he says this needs to be accompanied by different risk thresholds in the different risk areas.
Asked whether there is an argument that most individuals in low-risk countries may not need to take a statin, Dr. Mortensen countered: “One of the reasons the risk is low in many of these European countries is the high use of preventative medication. So, if a threshold that is too high is used most people will not take a statin anymore and the risk in these countries will increase again.”
Authors of the accompanying editorial, Ann Marie Navar, MD, PhD, University of Texas Southwestern Medical Center, Dallas; Gregg C. Fonarow, MD, University of California, Los Angeles; and Michael J. Pencina, PhD, Duke University Medical Center, Durham, N.C., agreed with Dr. Mortensen that the problems appear to arise from use of a risk score that is highly influenced by regional cardiovascular burden.
They point out that under the current guidelines, a 55-year-old woman (smoker; systolic blood pressure, 130 mm Hg; non–HDL cholesterol, 4.0 mmol/L) would have a 10-year predicted risk of having a cardiovascular event of 5% in Denmark but a predicted risk of 18% in Romania.
“While there may be regional differences in environmental risk factors, location alone should not cause a fourfold difference in an individual’s predicted cardiovascular risk,” they wrote.
The editorialists also elaborated on Dr. Mortensen’s point that the new guideline creates a system that eventually becomes a victim of its own success.
“As countries are successful in implementing statin therapy to lower CVD, CVD rates drop, and progressively fewer individuals are then eligible for the very therapy that contributed to the decline in CVD in the first place,” they noted.
The editorialists called for the analysis to be replicated in other low-risk countries and extended to higher-risk regions, with a focus on potential overtreatment of men and older adults.
“If confirmed, the present findings should be a catalyst for the ESC to revisit or augment their current guidelines to prevent a step backward in the use of statins in primary prevention,” they concluded.
This news organization asked the ESC for a response to the findings, but did not comment by press time.
This work was supported by the Lundbeck Foundation, Herlev and Gentofte Hospital, Copenhagen University Hospital, the Copenhagen County Foundation, and Aarhus University, Denmark. Dr. Mortensen reported no disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA CARDIOLOGY
Access to certified stroke centers divided by race, income
Hospitals in low-income and rural areas of the United States are much less likely to adopt stroke certification than hospitals in high-income and urban communities, a new study shows.
Further, other results showed that, after adjustment for population and hospital size, access to stroke-certified hospitals is significantly lower in Black, racially segregated communities.
The study was published online in JAMA Neurology.
Noting that stroke-certified hospitals provide higher-quality stroke care, the authors, led by Yu-Chu Shen, PhD, Naval Postgraduate School, Monterey, Calif., conclude that: “Our findings suggest that structural inequities in stroke care may be an important consideration in eliminating stroke disparities for vulnerable populations.”
In an audio interview on the JAMA Neurology website, senior author Renee Y. Hsia, MD, University of California, San Francisco, said: “Our findings show there are clear disparities in which communities are getting access to stroke certified hospitals.”
She called for more help for hospitals in underserved areas to obtain stroke certification.
Dr. Hsia explained that hospitals can seek certification at their own expense and that although stroke care is expensive, it is also lucrative in terms of reimbursement. So it tends to be the private for-profit hospitals that seek these certifications. “If you are a county hospital on a really tight budget, you’re not going to have the extra cash on hand to be applying for stroke certification,” she commented.
This can result in an increase in hospitals with stroke certification – but not in the areas that need it the most.
Dr. Hsia points out that this has happened in cardiac care. One study showed a 44% increase in hospitals providing percutaneous coronary intervention over a 10-year period, but the percentage of the population that had better access increased by less than 1%.
“In general, in the United States we have a mentality that ‘more is better,’ and because there is no government regulation in health care, any time a hospital applies for these specialized services we just generally think that’s a good thing. But this might not always be the case,” Dr. Hsia noted. “We have a very market-based approach, and this doesn’t lead to equity. It leads to profit maximization, and that is not synonymous with what’s good for patients or populations.”
She suggested that in future the process of certification should include some consideration of how it will affect population-based equity.
“Rather than rubber stamping an application just because hospitals have certain resources, we need to ask what the benefit is of providing this service,” Dr. Hsia said. “Does this community really need it? If not, maybe we should invest these resources into helping a hospital in a community that needs it more.”
Dr. Hsia explained that she and her colleagues conducted their study to investigate whether there were structural issues that might be contributing to disparities in stroke care.
“We like to think emergency stroke care is equitable. Anyone can call 911 or go the emergency room. But, actually, there is a big disparity on who receives what type of care,” she said. “We know Black patients are less likely to receive thrombolytics and mechanical thrombectomy compared to White patents. And wealthy patients are more likely to receive thrombectomy compared to patients from the poorest zip codes.”
She said there is a tendency to think this is a result of some sort of bias on the part of health care professionals. “We wanted to look deep down in the system and whether the built environment of health care supply and geographic distribution of services contributed to access and treatment inequities.”
The study combined a dataset of hospital stroke certification from all general acute nonfederal hospitals in the continental United States from January 2009 to December 2019. National, hospital, and census data were used to identify historically underserved communities by racial and ethnic composition, income distribution, and rurality.
A total of 4,984 hospitals were assessed. Results showed that over the 11-year study period, the number of hospitals with stroke certification grew from 961 (19%) to 1,763 (36%).
Without controlling for population and hospital size, hospitals in predominantly Black, racially segregated areas were 1.67-fold more likely to adopt stroke care of any level than those in predominantly non-Black, racially segregated areas (hazard ratio, 1.67; 95% confidence interval, 1.41-1.97).
However, after adjustment for population and hospital size, the likelihood of adopting stroke care among hospitals serving Black, racially segregated communities was significantly lower than among those serving non-Black, racially segregated communities (HR, 0.74; 95% CI, 0.62-0.89).
“In other words, on a per-capita basis, a hospital serving a predominantly Black, racially segregated community was 26% less likely to adopt stroke certification of any level than a hospital in a predominantly non-Black, racially segregated community,” the authors state.
In terms of socioeconomic factors, hospitals serving low-income, economically integrated (HR, 0.23) and low-income, economically segregated (HR, 0.29) areas were far less likely to adopt any level of stroke care certification than hospitals serving high-income areas, regardless of income segregation.
Rural hospitals were also much less likely to adopt any level of stroke care than urban hospitals (HR, 0.10).
“Our results suggest that it might be necessary to incentivize hospitals operating in underserved communities to seek stroke certification or to entice hospitals with higher propensity to adopt stroke care to operate in such communities so access at the per-patient level becomes more equitable,” the authors say.
This project was supported by the Pilot Project Award from the National Bureau of Economic Research Center for Aging and Health Research, funded by the National Institute on Aging and by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Shen and Dr. Hsia have received grants from the National Institute of Aging and the National Heart, Lung, and Blood Institute.
A version of this article first appeared on Medscape.com.
Hospitals in low-income and rural areas of the United States are much less likely to adopt stroke certification than hospitals in high-income and urban communities, a new study shows.
Further, other results showed that, after adjustment for population and hospital size, access to stroke-certified hospitals is significantly lower in Black, racially segregated communities.
The study was published online in JAMA Neurology.
Noting that stroke-certified hospitals provide higher-quality stroke care, the authors, led by Yu-Chu Shen, PhD, Naval Postgraduate School, Monterey, Calif., conclude that: “Our findings suggest that structural inequities in stroke care may be an important consideration in eliminating stroke disparities for vulnerable populations.”
In an audio interview on the JAMA Neurology website, senior author Renee Y. Hsia, MD, University of California, San Francisco, said: “Our findings show there are clear disparities in which communities are getting access to stroke certified hospitals.”
She called for more help for hospitals in underserved areas to obtain stroke certification.
Dr. Hsia explained that hospitals can seek certification at their own expense and that although stroke care is expensive, it is also lucrative in terms of reimbursement. So it tends to be the private for-profit hospitals that seek these certifications. “If you are a county hospital on a really tight budget, you’re not going to have the extra cash on hand to be applying for stroke certification,” she commented.
This can result in an increase in hospitals with stroke certification – but not in the areas that need it the most.
Dr. Hsia points out that this has happened in cardiac care. One study showed a 44% increase in hospitals providing percutaneous coronary intervention over a 10-year period, but the percentage of the population that had better access increased by less than 1%.
“In general, in the United States we have a mentality that ‘more is better,’ and because there is no government regulation in health care, any time a hospital applies for these specialized services we just generally think that’s a good thing. But this might not always be the case,” Dr. Hsia noted. “We have a very market-based approach, and this doesn’t lead to equity. It leads to profit maximization, and that is not synonymous with what’s good for patients or populations.”
She suggested that in future the process of certification should include some consideration of how it will affect population-based equity.
“Rather than rubber stamping an application just because hospitals have certain resources, we need to ask what the benefit is of providing this service,” Dr. Hsia said. “Does this community really need it? If not, maybe we should invest these resources into helping a hospital in a community that needs it more.”
Dr. Hsia explained that she and her colleagues conducted their study to investigate whether there were structural issues that might be contributing to disparities in stroke care.
“We like to think emergency stroke care is equitable. Anyone can call 911 or go the emergency room. But, actually, there is a big disparity on who receives what type of care,” she said. “We know Black patients are less likely to receive thrombolytics and mechanical thrombectomy compared to White patents. And wealthy patients are more likely to receive thrombectomy compared to patients from the poorest zip codes.”
She said there is a tendency to think this is a result of some sort of bias on the part of health care professionals. “We wanted to look deep down in the system and whether the built environment of health care supply and geographic distribution of services contributed to access and treatment inequities.”
The study combined a dataset of hospital stroke certification from all general acute nonfederal hospitals in the continental United States from January 2009 to December 2019. National, hospital, and census data were used to identify historically underserved communities by racial and ethnic composition, income distribution, and rurality.
A total of 4,984 hospitals were assessed. Results showed that over the 11-year study period, the number of hospitals with stroke certification grew from 961 (19%) to 1,763 (36%).
Without controlling for population and hospital size, hospitals in predominantly Black, racially segregated areas were 1.67-fold more likely to adopt stroke care of any level than those in predominantly non-Black, racially segregated areas (hazard ratio, 1.67; 95% confidence interval, 1.41-1.97).
However, after adjustment for population and hospital size, the likelihood of adopting stroke care among hospitals serving Black, racially segregated communities was significantly lower than among those serving non-Black, racially segregated communities (HR, 0.74; 95% CI, 0.62-0.89).
“In other words, on a per-capita basis, a hospital serving a predominantly Black, racially segregated community was 26% less likely to adopt stroke certification of any level than a hospital in a predominantly non-Black, racially segregated community,” the authors state.
In terms of socioeconomic factors, hospitals serving low-income, economically integrated (HR, 0.23) and low-income, economically segregated (HR, 0.29) areas were far less likely to adopt any level of stroke care certification than hospitals serving high-income areas, regardless of income segregation.
Rural hospitals were also much less likely to adopt any level of stroke care than urban hospitals (HR, 0.10).
“Our results suggest that it might be necessary to incentivize hospitals operating in underserved communities to seek stroke certification or to entice hospitals with higher propensity to adopt stroke care to operate in such communities so access at the per-patient level becomes more equitable,” the authors say.
This project was supported by the Pilot Project Award from the National Bureau of Economic Research Center for Aging and Health Research, funded by the National Institute on Aging and by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Shen and Dr. Hsia have received grants from the National Institute of Aging and the National Heart, Lung, and Blood Institute.
A version of this article first appeared on Medscape.com.
Hospitals in low-income and rural areas of the United States are much less likely to adopt stroke certification than hospitals in high-income and urban communities, a new study shows.
Further, other results showed that, after adjustment for population and hospital size, access to stroke-certified hospitals is significantly lower in Black, racially segregated communities.
The study was published online in JAMA Neurology.
Noting that stroke-certified hospitals provide higher-quality stroke care, the authors, led by Yu-Chu Shen, PhD, Naval Postgraduate School, Monterey, Calif., conclude that: “Our findings suggest that structural inequities in stroke care may be an important consideration in eliminating stroke disparities for vulnerable populations.”
In an audio interview on the JAMA Neurology website, senior author Renee Y. Hsia, MD, University of California, San Francisco, said: “Our findings show there are clear disparities in which communities are getting access to stroke certified hospitals.”
She called for more help for hospitals in underserved areas to obtain stroke certification.
Dr. Hsia explained that hospitals can seek certification at their own expense and that although stroke care is expensive, it is also lucrative in terms of reimbursement. So it tends to be the private for-profit hospitals that seek these certifications. “If you are a county hospital on a really tight budget, you’re not going to have the extra cash on hand to be applying for stroke certification,” she commented.
This can result in an increase in hospitals with stroke certification – but not in the areas that need it the most.
Dr. Hsia points out that this has happened in cardiac care. One study showed a 44% increase in hospitals providing percutaneous coronary intervention over a 10-year period, but the percentage of the population that had better access increased by less than 1%.
“In general, in the United States we have a mentality that ‘more is better,’ and because there is no government regulation in health care, any time a hospital applies for these specialized services we just generally think that’s a good thing. But this might not always be the case,” Dr. Hsia noted. “We have a very market-based approach, and this doesn’t lead to equity. It leads to profit maximization, and that is not synonymous with what’s good for patients or populations.”
She suggested that in future the process of certification should include some consideration of how it will affect population-based equity.
“Rather than rubber stamping an application just because hospitals have certain resources, we need to ask what the benefit is of providing this service,” Dr. Hsia said. “Does this community really need it? If not, maybe we should invest these resources into helping a hospital in a community that needs it more.”
Dr. Hsia explained that she and her colleagues conducted their study to investigate whether there were structural issues that might be contributing to disparities in stroke care.
“We like to think emergency stroke care is equitable. Anyone can call 911 or go the emergency room. But, actually, there is a big disparity on who receives what type of care,” she said. “We know Black patients are less likely to receive thrombolytics and mechanical thrombectomy compared to White patents. And wealthy patients are more likely to receive thrombectomy compared to patients from the poorest zip codes.”
She said there is a tendency to think this is a result of some sort of bias on the part of health care professionals. “We wanted to look deep down in the system and whether the built environment of health care supply and geographic distribution of services contributed to access and treatment inequities.”
The study combined a dataset of hospital stroke certification from all general acute nonfederal hospitals in the continental United States from January 2009 to December 2019. National, hospital, and census data were used to identify historically underserved communities by racial and ethnic composition, income distribution, and rurality.
A total of 4,984 hospitals were assessed. Results showed that over the 11-year study period, the number of hospitals with stroke certification grew from 961 (19%) to 1,763 (36%).
Without controlling for population and hospital size, hospitals in predominantly Black, racially segregated areas were 1.67-fold more likely to adopt stroke care of any level than those in predominantly non-Black, racially segregated areas (hazard ratio, 1.67; 95% confidence interval, 1.41-1.97).
However, after adjustment for population and hospital size, the likelihood of adopting stroke care among hospitals serving Black, racially segregated communities was significantly lower than among those serving non-Black, racially segregated communities (HR, 0.74; 95% CI, 0.62-0.89).
“In other words, on a per-capita basis, a hospital serving a predominantly Black, racially segregated community was 26% less likely to adopt stroke certification of any level than a hospital in a predominantly non-Black, racially segregated community,” the authors state.
In terms of socioeconomic factors, hospitals serving low-income, economically integrated (HR, 0.23) and low-income, economically segregated (HR, 0.29) areas were far less likely to adopt any level of stroke care certification than hospitals serving high-income areas, regardless of income segregation.
Rural hospitals were also much less likely to adopt any level of stroke care than urban hospitals (HR, 0.10).
“Our results suggest that it might be necessary to incentivize hospitals operating in underserved communities to seek stroke certification or to entice hospitals with higher propensity to adopt stroke care to operate in such communities so access at the per-patient level becomes more equitable,” the authors say.
This project was supported by the Pilot Project Award from the National Bureau of Economic Research Center for Aging and Health Research, funded by the National Institute on Aging and by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Shen and Dr. Hsia have received grants from the National Institute of Aging and the National Heart, Lung, and Blood Institute.
A version of this article first appeared on Medscape.com.
New biomarker data add to concerns over REDUCE-IT trial
A new analysis of the REDUCE-IT study has reignited concerns that the benefit shown by the high-dose fish oil product in the study, icosapent ethyl (Vascepa, Amarin), may have been related to harms caused by the placebo mineral oil.
Results show that allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels of these biomarkers increased among those allocated to mineral oil.
At 12 months, the median percent increases from baseline in the mineral oil group were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density-lipoprotein (LDL) cholesterol, 16.2% for interleukin (IL)-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein (hsCRP), and 28.9% for IL-1β. The changes were similar at 24 months. However, in the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months.
The study was published online in Circulation.
The authors, led by Paul Ridker, MD, Brigham & Women’s Hospital, Boston, do not voice much opinion on what the results mean, concluding that “the effect of these findings on the interpretation of the REDUCE-IT trial results remains unclear and will require further investigation.”
They also say that a second icosapent ethyl trial using a nonmineral oil comparator “would help resolve ongoing controversy.”
However, the authors are a mixed group; Dr. Ridker and some of his coauthors were not part of the original REDUCE-IT trial, whereas other coauthors were members of the REDUCE-IT steering committee, and one was an employee of Amarin.
Lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, also from Brigham & Women’s Hospital, who is the senior author of the current study, played down the new findings, saying they did not offer much new incremental information on mechanistic insight.
“These are small degrees of biomarker increases on an absolute level we are seeing with the placebo that would not be expected to produce harm,” Dr. Bhatt told this news organization. He also said the Circulation peer-review process had removed some of the discussion, which could lead to some “misinterpretation” of the authors’ views.
Dr. Ridker was unavailable for further comment.
The publication of this study has inevitably poured fuel on the fire regarding the controversy that has long dogged the REDUCE-IT trial, with questions about the large reduction in event rates seen with icosapent ethyl without an obvious mechanistic explanation.
‘Smoking gun’
One of the loudest critics of the study, Steve Nissen, MD, Cleveland Clinic, described the new findings as “the closest thing I’ve seen to a smoking gun in medicine for a long, long time.”
“The result of this new analysis shows that mineral oil increases virtually every inflammatory and lipid marker that they measured,” he commented.
“There are a lot of theories, but the bottom line is that something really bad happened in the mineral-oil group, which makes icosapent ethyl look efficacious. In my view, this needs to be reviewed by the FDA for consideration of removing the label claim for cardiovascular benefit.”
Other experts in the field not directly involved in the study voiced concern about these new findings, adding to calls for another trial.
In a Twitter thread on the issue, Harlan Krumholz, MD, describes the Circulation publication as “an exceptionally important article,” adding that it is “time to rethink this drug.”
“My point is ... once you know you have non-neutral comparator and the effect on risk biomarkers is far from trivial ... then you have introduced substantial uncertainty about the trial result, as conveyed by the authors ... and no one can say what would happen with a neutral comparator,” Dr. Krumholz writes.
In an accompanying editorial in Circulation, Robert Harrington, MD, professor of medicine at Stanford (Calif.) University, concludes that “the hard reality is that we are left with uncertainties and the questions raised by use of the mineral oil as placebo can only be answered by another randomized controlled trial.”
“My main points are that the chosen placebo was not inert (an essential characteristic for an active control–placebo comparison), that the biomarker data show elevations in multiple markers involved with inflammatory pathways associated with atherosclerosis, and that these data create enough uncertainty in the trial interpretation that the best recourse to answer the criticisms is to do another trial with a truly inert placebo,” Dr. Harrington said in an interview.
He added that Dr. Bhatt’s point that the changes in biomarkers are too small to really matter clinically may be right. “But for me, the uncertainties mean that I have less confidence in the true magnitude of the treatment effect than I would have if there were no changes in the inflammatory markers.”
In Circulation, the authors say it is unclear why multiple biomarkers increased over time among REDUCE-IT participants allocated to mineral oil. They note that no substantive changes in these biomarkers were observed in the placebo groups over periods of 3-5 years in other trials, including JUPITER, CIRT, CANTOS, SPIRE, and the STRENGTH trials, which evaluated a different high-dose omega-3 oil product but used corn oil as the placebo.
“The core design of REDUCE-IT does not make it possible to resolve convincingly whether any adverse effects associated with mineral oil use as a comparator may have affected clinical outcomes,” they write.
They point out that regulatory agencies evaluating REDUCE-IT estimated that approximately 3% of the net clinical benefit observed with icosapent ethyl might have been a consequence of adverse biomarker effects on LDL cholesterol and hsCRP attributable to mineral oil. But in the context of an overall 25% relative risk reduction in first events and a 30% reduction in total ischemic events observed, a potential bias of this magnitude, even if doubled in size, would be unlikely to fully attenuate the overall benefit of icosapent ethyl observed.
They add that they are not aware of a method to assess what the potential magnitude might be of a combination of the multiple effects.
New data do not change the debate
“We did a large, well-powered randomized trial, and this paper shouldn’t change anything in how that trial should be interpreted,” Dr. Bhatt said in an interview.
He claims the new biomarkers evaluated in the study are correlated with LDL and CRP, data which have already been reported and analyzed so have limited relevance.
“It’s not really independent biomarker information; this is what we would expect to see when we see small increases in LDL and CRP. So, I don’t think this new information fundamentally changes the debate,” he said.
Dr. Bhatt also pointed out that the study highlights relative increases rather than absolute increases in the biomarkers, making it seem more alarming than is actually the case.
“The paper makes it seem like that there are large increases in these other biomarkers, but the values reported are relative increases and the absolute increases were actually rather small. In many cases, the changes reported are less than the lower limit of quantification of the assay used,” he noted.
He added: “Even if one is unable to get around the placebo issue in the REDUCE-IT trial, there will always be the JELIS trial – a randomized trial with no placebo showing a 19% relative risk reduction. While the biomarker data may be interesting, what really matters in the end is clinical events. And significant reductions in two independent trials should be enough.”
Dr. Bhatt says the REDUCE-IT steering committee does not believe another trial is needed. “Maybe a different population would be good – such as primary prevention, patients without elevated triglycerides – but just repeating REDUCE- IT with a different placebo would be a waste of resources,” he commented.
But Dr. Nissen refuted Dr. Bhatt’s claims.
“These biomarkers are not in the same pathways as LDL and CRP, and these are not small increases. In the CANTOS trial, a monoclonal antibody against interleukin-1β beta showed a significant benefit. The increase in interleukin-1β now reported in REDUCE-IT is exactly the opposite of CANTOS,” he pointed out.
“The FDA did not know about these additional biomarkers when it reviewed the data on LDL and CRP. Now we have new information. It needs to be looked at again,” Dr. Nissen added.
Funding for the study was provided by Amarin Pharma. Dr. Bhatt was the lead investigator of the REDUCE-IT trial. Dr. Nissen was the lead investigator the STRENGTH trial. Further disclosures of the authors can be found in Circulation.
A version of this article first appeared on Medscape.com.
A new analysis of the REDUCE-IT study has reignited concerns that the benefit shown by the high-dose fish oil product in the study, icosapent ethyl (Vascepa, Amarin), may have been related to harms caused by the placebo mineral oil.
Results show that allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels of these biomarkers increased among those allocated to mineral oil.
At 12 months, the median percent increases from baseline in the mineral oil group were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density-lipoprotein (LDL) cholesterol, 16.2% for interleukin (IL)-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein (hsCRP), and 28.9% for IL-1β. The changes were similar at 24 months. However, in the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months.
The study was published online in Circulation.
The authors, led by Paul Ridker, MD, Brigham & Women’s Hospital, Boston, do not voice much opinion on what the results mean, concluding that “the effect of these findings on the interpretation of the REDUCE-IT trial results remains unclear and will require further investigation.”
They also say that a second icosapent ethyl trial using a nonmineral oil comparator “would help resolve ongoing controversy.”
However, the authors are a mixed group; Dr. Ridker and some of his coauthors were not part of the original REDUCE-IT trial, whereas other coauthors were members of the REDUCE-IT steering committee, and one was an employee of Amarin.
Lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, also from Brigham & Women’s Hospital, who is the senior author of the current study, played down the new findings, saying they did not offer much new incremental information on mechanistic insight.
“These are small degrees of biomarker increases on an absolute level we are seeing with the placebo that would not be expected to produce harm,” Dr. Bhatt told this news organization. He also said the Circulation peer-review process had removed some of the discussion, which could lead to some “misinterpretation” of the authors’ views.
Dr. Ridker was unavailable for further comment.
The publication of this study has inevitably poured fuel on the fire regarding the controversy that has long dogged the REDUCE-IT trial, with questions about the large reduction in event rates seen with icosapent ethyl without an obvious mechanistic explanation.
‘Smoking gun’
One of the loudest critics of the study, Steve Nissen, MD, Cleveland Clinic, described the new findings as “the closest thing I’ve seen to a smoking gun in medicine for a long, long time.”
“The result of this new analysis shows that mineral oil increases virtually every inflammatory and lipid marker that they measured,” he commented.
“There are a lot of theories, but the bottom line is that something really bad happened in the mineral-oil group, which makes icosapent ethyl look efficacious. In my view, this needs to be reviewed by the FDA for consideration of removing the label claim for cardiovascular benefit.”
Other experts in the field not directly involved in the study voiced concern about these new findings, adding to calls for another trial.
In a Twitter thread on the issue, Harlan Krumholz, MD, describes the Circulation publication as “an exceptionally important article,” adding that it is “time to rethink this drug.”
“My point is ... once you know you have non-neutral comparator and the effect on risk biomarkers is far from trivial ... then you have introduced substantial uncertainty about the trial result, as conveyed by the authors ... and no one can say what would happen with a neutral comparator,” Dr. Krumholz writes.
In an accompanying editorial in Circulation, Robert Harrington, MD, professor of medicine at Stanford (Calif.) University, concludes that “the hard reality is that we are left with uncertainties and the questions raised by use of the mineral oil as placebo can only be answered by another randomized controlled trial.”
“My main points are that the chosen placebo was not inert (an essential characteristic for an active control–placebo comparison), that the biomarker data show elevations in multiple markers involved with inflammatory pathways associated with atherosclerosis, and that these data create enough uncertainty in the trial interpretation that the best recourse to answer the criticisms is to do another trial with a truly inert placebo,” Dr. Harrington said in an interview.
He added that Dr. Bhatt’s point that the changes in biomarkers are too small to really matter clinically may be right. “But for me, the uncertainties mean that I have less confidence in the true magnitude of the treatment effect than I would have if there were no changes in the inflammatory markers.”
In Circulation, the authors say it is unclear why multiple biomarkers increased over time among REDUCE-IT participants allocated to mineral oil. They note that no substantive changes in these biomarkers were observed in the placebo groups over periods of 3-5 years in other trials, including JUPITER, CIRT, CANTOS, SPIRE, and the STRENGTH trials, which evaluated a different high-dose omega-3 oil product but used corn oil as the placebo.
“The core design of REDUCE-IT does not make it possible to resolve convincingly whether any adverse effects associated with mineral oil use as a comparator may have affected clinical outcomes,” they write.
They point out that regulatory agencies evaluating REDUCE-IT estimated that approximately 3% of the net clinical benefit observed with icosapent ethyl might have been a consequence of adverse biomarker effects on LDL cholesterol and hsCRP attributable to mineral oil. But in the context of an overall 25% relative risk reduction in first events and a 30% reduction in total ischemic events observed, a potential bias of this magnitude, even if doubled in size, would be unlikely to fully attenuate the overall benefit of icosapent ethyl observed.
They add that they are not aware of a method to assess what the potential magnitude might be of a combination of the multiple effects.
New data do not change the debate
“We did a large, well-powered randomized trial, and this paper shouldn’t change anything in how that trial should be interpreted,” Dr. Bhatt said in an interview.
He claims the new biomarkers evaluated in the study are correlated with LDL and CRP, data which have already been reported and analyzed so have limited relevance.
“It’s not really independent biomarker information; this is what we would expect to see when we see small increases in LDL and CRP. So, I don’t think this new information fundamentally changes the debate,” he said.
Dr. Bhatt also pointed out that the study highlights relative increases rather than absolute increases in the biomarkers, making it seem more alarming than is actually the case.
“The paper makes it seem like that there are large increases in these other biomarkers, but the values reported are relative increases and the absolute increases were actually rather small. In many cases, the changes reported are less than the lower limit of quantification of the assay used,” he noted.
He added: “Even if one is unable to get around the placebo issue in the REDUCE-IT trial, there will always be the JELIS trial – a randomized trial with no placebo showing a 19% relative risk reduction. While the biomarker data may be interesting, what really matters in the end is clinical events. And significant reductions in two independent trials should be enough.”
Dr. Bhatt says the REDUCE-IT steering committee does not believe another trial is needed. “Maybe a different population would be good – such as primary prevention, patients without elevated triglycerides – but just repeating REDUCE- IT with a different placebo would be a waste of resources,” he commented.
But Dr. Nissen refuted Dr. Bhatt’s claims.
“These biomarkers are not in the same pathways as LDL and CRP, and these are not small increases. In the CANTOS trial, a monoclonal antibody against interleukin-1β beta showed a significant benefit. The increase in interleukin-1β now reported in REDUCE-IT is exactly the opposite of CANTOS,” he pointed out.
“The FDA did not know about these additional biomarkers when it reviewed the data on LDL and CRP. Now we have new information. It needs to be looked at again,” Dr. Nissen added.
Funding for the study was provided by Amarin Pharma. Dr. Bhatt was the lead investigator of the REDUCE-IT trial. Dr. Nissen was the lead investigator the STRENGTH trial. Further disclosures of the authors can be found in Circulation.
A version of this article first appeared on Medscape.com.
A new analysis of the REDUCE-IT study has reignited concerns that the benefit shown by the high-dose fish oil product in the study, icosapent ethyl (Vascepa, Amarin), may have been related to harms caused by the placebo mineral oil.
Results show that allocation to icosapent ethyl had minimal effects on a series of biomarkers associated with atherosclerotic disease, whereas levels of these biomarkers increased among those allocated to mineral oil.
At 12 months, the median percent increases from baseline in the mineral oil group were 1.5% for homocysteine, 2.2% for lipoprotein(a), 10.9% for oxidized low-density-lipoprotein (LDL) cholesterol, 16.2% for interleukin (IL)-6, 18.5% for lipoprotein-associated phospholipase A2, 21.9% for high-sensitivity C-reactive protein (hsCRP), and 28.9% for IL-1β. The changes were similar at 24 months. However, in the icosapent ethyl group, there were minimal changes in these biomarkers at 12 and 24 months.
The study was published online in Circulation.
The authors, led by Paul Ridker, MD, Brigham & Women’s Hospital, Boston, do not voice much opinion on what the results mean, concluding that “the effect of these findings on the interpretation of the REDUCE-IT trial results remains unclear and will require further investigation.”
They also say that a second icosapent ethyl trial using a nonmineral oil comparator “would help resolve ongoing controversy.”
However, the authors are a mixed group; Dr. Ridker and some of his coauthors were not part of the original REDUCE-IT trial, whereas other coauthors were members of the REDUCE-IT steering committee, and one was an employee of Amarin.
Lead investigator of the REDUCE-IT trial, Deepak Bhatt, MD, also from Brigham & Women’s Hospital, who is the senior author of the current study, played down the new findings, saying they did not offer much new incremental information on mechanistic insight.
“These are small degrees of biomarker increases on an absolute level we are seeing with the placebo that would not be expected to produce harm,” Dr. Bhatt told this news organization. He also said the Circulation peer-review process had removed some of the discussion, which could lead to some “misinterpretation” of the authors’ views.
Dr. Ridker was unavailable for further comment.
The publication of this study has inevitably poured fuel on the fire regarding the controversy that has long dogged the REDUCE-IT trial, with questions about the large reduction in event rates seen with icosapent ethyl without an obvious mechanistic explanation.
‘Smoking gun’
One of the loudest critics of the study, Steve Nissen, MD, Cleveland Clinic, described the new findings as “the closest thing I’ve seen to a smoking gun in medicine for a long, long time.”
“The result of this new analysis shows that mineral oil increases virtually every inflammatory and lipid marker that they measured,” he commented.
“There are a lot of theories, but the bottom line is that something really bad happened in the mineral-oil group, which makes icosapent ethyl look efficacious. In my view, this needs to be reviewed by the FDA for consideration of removing the label claim for cardiovascular benefit.”
Other experts in the field not directly involved in the study voiced concern about these new findings, adding to calls for another trial.
In a Twitter thread on the issue, Harlan Krumholz, MD, describes the Circulation publication as “an exceptionally important article,” adding that it is “time to rethink this drug.”
“My point is ... once you know you have non-neutral comparator and the effect on risk biomarkers is far from trivial ... then you have introduced substantial uncertainty about the trial result, as conveyed by the authors ... and no one can say what would happen with a neutral comparator,” Dr. Krumholz writes.
In an accompanying editorial in Circulation, Robert Harrington, MD, professor of medicine at Stanford (Calif.) University, concludes that “the hard reality is that we are left with uncertainties and the questions raised by use of the mineral oil as placebo can only be answered by another randomized controlled trial.”
“My main points are that the chosen placebo was not inert (an essential characteristic for an active control–placebo comparison), that the biomarker data show elevations in multiple markers involved with inflammatory pathways associated with atherosclerosis, and that these data create enough uncertainty in the trial interpretation that the best recourse to answer the criticisms is to do another trial with a truly inert placebo,” Dr. Harrington said in an interview.
He added that Dr. Bhatt’s point that the changes in biomarkers are too small to really matter clinically may be right. “But for me, the uncertainties mean that I have less confidence in the true magnitude of the treatment effect than I would have if there were no changes in the inflammatory markers.”
In Circulation, the authors say it is unclear why multiple biomarkers increased over time among REDUCE-IT participants allocated to mineral oil. They note that no substantive changes in these biomarkers were observed in the placebo groups over periods of 3-5 years in other trials, including JUPITER, CIRT, CANTOS, SPIRE, and the STRENGTH trials, which evaluated a different high-dose omega-3 oil product but used corn oil as the placebo.
“The core design of REDUCE-IT does not make it possible to resolve convincingly whether any adverse effects associated with mineral oil use as a comparator may have affected clinical outcomes,” they write.
They point out that regulatory agencies evaluating REDUCE-IT estimated that approximately 3% of the net clinical benefit observed with icosapent ethyl might have been a consequence of adverse biomarker effects on LDL cholesterol and hsCRP attributable to mineral oil. But in the context of an overall 25% relative risk reduction in first events and a 30% reduction in total ischemic events observed, a potential bias of this magnitude, even if doubled in size, would be unlikely to fully attenuate the overall benefit of icosapent ethyl observed.
They add that they are not aware of a method to assess what the potential magnitude might be of a combination of the multiple effects.
New data do not change the debate
“We did a large, well-powered randomized trial, and this paper shouldn’t change anything in how that trial should be interpreted,” Dr. Bhatt said in an interview.
He claims the new biomarkers evaluated in the study are correlated with LDL and CRP, data which have already been reported and analyzed so have limited relevance.
“It’s not really independent biomarker information; this is what we would expect to see when we see small increases in LDL and CRP. So, I don’t think this new information fundamentally changes the debate,” he said.
Dr. Bhatt also pointed out that the study highlights relative increases rather than absolute increases in the biomarkers, making it seem more alarming than is actually the case.
“The paper makes it seem like that there are large increases in these other biomarkers, but the values reported are relative increases and the absolute increases were actually rather small. In many cases, the changes reported are less than the lower limit of quantification of the assay used,” he noted.
He added: “Even if one is unable to get around the placebo issue in the REDUCE-IT trial, there will always be the JELIS trial – a randomized trial with no placebo showing a 19% relative risk reduction. While the biomarker data may be interesting, what really matters in the end is clinical events. And significant reductions in two independent trials should be enough.”
Dr. Bhatt says the REDUCE-IT steering committee does not believe another trial is needed. “Maybe a different population would be good – such as primary prevention, patients without elevated triglycerides – but just repeating REDUCE- IT with a different placebo would be a waste of resources,” he commented.
But Dr. Nissen refuted Dr. Bhatt’s claims.
“These biomarkers are not in the same pathways as LDL and CRP, and these are not small increases. In the CANTOS trial, a monoclonal antibody against interleukin-1β beta showed a significant benefit. The increase in interleukin-1β now reported in REDUCE-IT is exactly the opposite of CANTOS,” he pointed out.
“The FDA did not know about these additional biomarkers when it reviewed the data on LDL and CRP. Now we have new information. It needs to be looked at again,” Dr. Nissen added.
Funding for the study was provided by Amarin Pharma. Dr. Bhatt was the lead investigator of the REDUCE-IT trial. Dr. Nissen was the lead investigator the STRENGTH trial. Further disclosures of the authors can be found in Circulation.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
Study confirms increased CVT with AstraZeneca COVID vaccine
A new Scandinavian study has confirmed previous data showing increased rates of cerebral venous thrombosis and thrombocytopenia after the AstraZeneca COVID-19 vaccine.
The study also showed higher rates of several thromboembolic and thrombocytopenic outcomes after the Pfizer and Moderna mRNA vaccines, although these increases were less than the rates observed after the AstraZeneca vaccine, and sensitivity analyses were not consistent.
The researchers conclude that confirmatory analysis on the two mRNA vaccines by other methods are warranted.
The study was published in the June issue of JAMA Network Open.
“This study confirms what we know from other studies: that the AstraZeneca vaccine is associated with the rare but serious side effect of vaccine-induced immune thrombotic thrombocytopenia,” lead author Jacob Dag Berild, MD, Norwegian Institute of Public Health, Oslo, told this news organization.
he added.
Dr. Dag Berild noted that in the current study there was an excess of 1.6 events of cerebral venous thrombosis per 100,000 AstraZeneca vaccine doses, which is similar to what has been previously reported.
Asked how he saw these results affecting continued use of these vaccines, Dr. Dag Berild pointed out that the risk-benefit ratio of the vaccine depends on the risk of contracting COVID-19 and the risk for a severe outcome from COVID-19 weighed against the risk for an adverse event after vaccination.
“The European Medicines Agency has concluded that the overall risk-benefit ratio remains positive for the AstraZeneca vaccine, but Norway, Finland, and Denmark no longer use the AstraZeneca vaccine in their vaccination programs because of adequate availability of alternative vaccines. I think this is a reasonable decision,” he said.
For the current study, the researchers linked individual-level data separately from national population, patient, and vaccination registers in Norway, Finland, and Denmark. Patient registers were used to identify hospital visits and admissions related to thromboembolic and thrombocytopenic disease in all three countries.
The main outcomes were relative rates of coronary artery disease, coagulation disorders, and cerebrovascular disease in the 28-day period after vaccination, compared with the control period prior to vaccination.
The authors note that a strength of this study is the use of registers with full population coverage in three countries with universal health care, ensuring equal access to care for all permanent residents. At the end of the study period, from Jan. 1, 2020 to May 16, 2021, more than 5.3 million people in the three countries were vaccinated with one or two doses.
Another strength is the inherent adjustment for time-invariant confounders in the self-controlled case series design and the resulting control of confounders that can affect the more traditional observational studies when complete data for confounders are not available, they add.
Of the 265,339 hospital contacts, 43% were made by female patients and 93% by patients born in or before 1971, and 44% were for coronary artery disease, 21% for coagulation disorders, and 35% for cerebrovascular disease.
In the 28-day period after vaccination, there was an elevated rate of coronary artery disease after the Moderna vaccine (relative rate, 1.13) but not after the AstraZeneca (RR, 0.92) or Pfizer (RR, 0.96) vaccines.
There was an observed increase in the rate of coagulation disorders after all three vaccines (AstraZeneca RR, 2.01; Pfizer RR, 1.12; and Moderna RR, 1.26).
There was also an increase in the rate of cerebrovascular disease after all three vaccines (AstraZeneca RR, 1.32; Pfizer RR, 1.09; and Moderna RR, 1.21).
For individual diseases in the main outcomes, two notably high rates were observed after the AstraZeneca vaccine, with relative rates of 12.04 for cerebral venous thrombosis and 4.29 for thrombocytopenia, corresponding to 1.6 and 4.9 excess events per 100,000 doses, respectively.
The elevated risk after the AstraZeneca vaccine was consistent across all three countries and robust in sensitivity analyses.
The researchers report that they also observed statistically significant increases in hospital contacts for thrombocytopenic and thromboembolic events after the Pfizer and Moderna vaccines. However, the risk was smaller than after the AstraZeneca vaccine.
“Additionally, the national estimates varied, increased risk [was] observed only in the oldest cohorts, and sensitivity analysis checking underlying assumptions of the analyses were not consistent. Therefore, the overall and combined increased relative risks following the Pfizer and Moderna vaccinations should be interpreted with caution,” they say.
They note that their results with the AstraZeneca vaccine are in line with a comparison of observed and historic rates performed on partly the same population in Norway and Denmark and also with a Scottish national case-control study.
A version of this article first appeared on Medscape.com.
A new Scandinavian study has confirmed previous data showing increased rates of cerebral venous thrombosis and thrombocytopenia after the AstraZeneca COVID-19 vaccine.
The study also showed higher rates of several thromboembolic and thrombocytopenic outcomes after the Pfizer and Moderna mRNA vaccines, although these increases were less than the rates observed after the AstraZeneca vaccine, and sensitivity analyses were not consistent.
The researchers conclude that confirmatory analysis on the two mRNA vaccines by other methods are warranted.
The study was published in the June issue of JAMA Network Open.
“This study confirms what we know from other studies: that the AstraZeneca vaccine is associated with the rare but serious side effect of vaccine-induced immune thrombotic thrombocytopenia,” lead author Jacob Dag Berild, MD, Norwegian Institute of Public Health, Oslo, told this news organization.
he added.
Dr. Dag Berild noted that in the current study there was an excess of 1.6 events of cerebral venous thrombosis per 100,000 AstraZeneca vaccine doses, which is similar to what has been previously reported.
Asked how he saw these results affecting continued use of these vaccines, Dr. Dag Berild pointed out that the risk-benefit ratio of the vaccine depends on the risk of contracting COVID-19 and the risk for a severe outcome from COVID-19 weighed against the risk for an adverse event after vaccination.
“The European Medicines Agency has concluded that the overall risk-benefit ratio remains positive for the AstraZeneca vaccine, but Norway, Finland, and Denmark no longer use the AstraZeneca vaccine in their vaccination programs because of adequate availability of alternative vaccines. I think this is a reasonable decision,” he said.
For the current study, the researchers linked individual-level data separately from national population, patient, and vaccination registers in Norway, Finland, and Denmark. Patient registers were used to identify hospital visits and admissions related to thromboembolic and thrombocytopenic disease in all three countries.
The main outcomes were relative rates of coronary artery disease, coagulation disorders, and cerebrovascular disease in the 28-day period after vaccination, compared with the control period prior to vaccination.
The authors note that a strength of this study is the use of registers with full population coverage in three countries with universal health care, ensuring equal access to care for all permanent residents. At the end of the study period, from Jan. 1, 2020 to May 16, 2021, more than 5.3 million people in the three countries were vaccinated with one or two doses.
Another strength is the inherent adjustment for time-invariant confounders in the self-controlled case series design and the resulting control of confounders that can affect the more traditional observational studies when complete data for confounders are not available, they add.
Of the 265,339 hospital contacts, 43% were made by female patients and 93% by patients born in or before 1971, and 44% were for coronary artery disease, 21% for coagulation disorders, and 35% for cerebrovascular disease.
In the 28-day period after vaccination, there was an elevated rate of coronary artery disease after the Moderna vaccine (relative rate, 1.13) but not after the AstraZeneca (RR, 0.92) or Pfizer (RR, 0.96) vaccines.
There was an observed increase in the rate of coagulation disorders after all three vaccines (AstraZeneca RR, 2.01; Pfizer RR, 1.12; and Moderna RR, 1.26).
There was also an increase in the rate of cerebrovascular disease after all three vaccines (AstraZeneca RR, 1.32; Pfizer RR, 1.09; and Moderna RR, 1.21).
For individual diseases in the main outcomes, two notably high rates were observed after the AstraZeneca vaccine, with relative rates of 12.04 for cerebral venous thrombosis and 4.29 for thrombocytopenia, corresponding to 1.6 and 4.9 excess events per 100,000 doses, respectively.
The elevated risk after the AstraZeneca vaccine was consistent across all three countries and robust in sensitivity analyses.
The researchers report that they also observed statistically significant increases in hospital contacts for thrombocytopenic and thromboembolic events after the Pfizer and Moderna vaccines. However, the risk was smaller than after the AstraZeneca vaccine.
“Additionally, the national estimates varied, increased risk [was] observed only in the oldest cohorts, and sensitivity analysis checking underlying assumptions of the analyses were not consistent. Therefore, the overall and combined increased relative risks following the Pfizer and Moderna vaccinations should be interpreted with caution,” they say.
They note that their results with the AstraZeneca vaccine are in line with a comparison of observed and historic rates performed on partly the same population in Norway and Denmark and also with a Scottish national case-control study.
A version of this article first appeared on Medscape.com.
A new Scandinavian study has confirmed previous data showing increased rates of cerebral venous thrombosis and thrombocytopenia after the AstraZeneca COVID-19 vaccine.
The study also showed higher rates of several thromboembolic and thrombocytopenic outcomes after the Pfizer and Moderna mRNA vaccines, although these increases were less than the rates observed after the AstraZeneca vaccine, and sensitivity analyses were not consistent.
The researchers conclude that confirmatory analysis on the two mRNA vaccines by other methods are warranted.
The study was published in the June issue of JAMA Network Open.
“This study confirms what we know from other studies: that the AstraZeneca vaccine is associated with the rare but serious side effect of vaccine-induced immune thrombotic thrombocytopenia,” lead author Jacob Dag Berild, MD, Norwegian Institute of Public Health, Oslo, told this news organization.
he added.
Dr. Dag Berild noted that in the current study there was an excess of 1.6 events of cerebral venous thrombosis per 100,000 AstraZeneca vaccine doses, which is similar to what has been previously reported.
Asked how he saw these results affecting continued use of these vaccines, Dr. Dag Berild pointed out that the risk-benefit ratio of the vaccine depends on the risk of contracting COVID-19 and the risk for a severe outcome from COVID-19 weighed against the risk for an adverse event after vaccination.
“The European Medicines Agency has concluded that the overall risk-benefit ratio remains positive for the AstraZeneca vaccine, but Norway, Finland, and Denmark no longer use the AstraZeneca vaccine in their vaccination programs because of adequate availability of alternative vaccines. I think this is a reasonable decision,” he said.
For the current study, the researchers linked individual-level data separately from national population, patient, and vaccination registers in Norway, Finland, and Denmark. Patient registers were used to identify hospital visits and admissions related to thromboembolic and thrombocytopenic disease in all three countries.
The main outcomes were relative rates of coronary artery disease, coagulation disorders, and cerebrovascular disease in the 28-day period after vaccination, compared with the control period prior to vaccination.
The authors note that a strength of this study is the use of registers with full population coverage in three countries with universal health care, ensuring equal access to care for all permanent residents. At the end of the study period, from Jan. 1, 2020 to May 16, 2021, more than 5.3 million people in the three countries were vaccinated with one or two doses.
Another strength is the inherent adjustment for time-invariant confounders in the self-controlled case series design and the resulting control of confounders that can affect the more traditional observational studies when complete data for confounders are not available, they add.
Of the 265,339 hospital contacts, 43% were made by female patients and 93% by patients born in or before 1971, and 44% were for coronary artery disease, 21% for coagulation disorders, and 35% for cerebrovascular disease.
In the 28-day period after vaccination, there was an elevated rate of coronary artery disease after the Moderna vaccine (relative rate, 1.13) but not after the AstraZeneca (RR, 0.92) or Pfizer (RR, 0.96) vaccines.
There was an observed increase in the rate of coagulation disorders after all three vaccines (AstraZeneca RR, 2.01; Pfizer RR, 1.12; and Moderna RR, 1.26).
There was also an increase in the rate of cerebrovascular disease after all three vaccines (AstraZeneca RR, 1.32; Pfizer RR, 1.09; and Moderna RR, 1.21).
For individual diseases in the main outcomes, two notably high rates were observed after the AstraZeneca vaccine, with relative rates of 12.04 for cerebral venous thrombosis and 4.29 for thrombocytopenia, corresponding to 1.6 and 4.9 excess events per 100,000 doses, respectively.
The elevated risk after the AstraZeneca vaccine was consistent across all three countries and robust in sensitivity analyses.
The researchers report that they also observed statistically significant increases in hospital contacts for thrombocytopenic and thromboembolic events after the Pfizer and Moderna vaccines. However, the risk was smaller than after the AstraZeneca vaccine.
“Additionally, the national estimates varied, increased risk [was] observed only in the oldest cohorts, and sensitivity analysis checking underlying assumptions of the analyses were not consistent. Therefore, the overall and combined increased relative risks following the Pfizer and Moderna vaccinations should be interpreted with caution,” they say.
They note that their results with the AstraZeneca vaccine are in line with a comparison of observed and historic rates performed on partly the same population in Norway and Denmark and also with a Scottish national case-control study.
A version of this article first appeared on Medscape.com.
Thigh muscle fat predicts risk of developing heart failure
in a new study. The association was independent of other cardiometabolic risk factors and measures of adiposity such as body mass index.
The observation raises the possibility of new avenues of research aimed at modifying intramuscular fat levels as a strategy to reduce the risk of developing heart failure.
The study was published online in JACC: Heart Failure.
The authors, led by Kevin Huynh, MD, University of Texas Southwestern Medical Center, Dallas, explained that obesity is a known risk for heart failure, and has been incorporated into risk calculators for heart failure.
However, obesity is a complex and heterogeneous disease with substantial regional variability of adipose deposition in body tissues, they noted. For example, variability in visceral adipose tissue and subcutaneous adipose tissue has been shown to have a differential impact on both cardiovascular risk factors and clinical cardiovascular disease outcomes.
The fat deposition around and within nonadipose tissues (termed “ectopic fat”), such as skeletal muscle, is also a known risk factor for cardiovascular disease, independent of adiposity. However, the impact of peripheral skeletal muscle fat deposition on heart failure risk is not as well studied.
The researchers noted that ectopic fat in skeletal muscle can be measured through imaging and categorized as either intermuscular or intramuscular fat according to the location of muscle fat around or within skeletal muscle, respectively.
The researchers conducted the current study to characterize the association of both intermuscular and intramuscular fat deposition with heart failure risk in a large cohort of older adults.
They used data from 2,399 individuals aged 70-79 years without heart failure at baseline who participated in the Health ABC (Health, Aging and Body Composition) study. Measures of intramuscular and intermuscular fat in the thigh were determined by CT, and the participants were followed for an average of 12 years.
During the follow-up period, there were 485 incident heart failure events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with heart failure risk.
After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was significantly associated with higher risk for heart failure.
Individuals in the highest tertile of intramuscular fat had a 34% increased risk of developing heart failure, compared with those in the lowest tertile. This finding was independent of other cardiometabolic risk factors, measures of adiposity including body mass index and percent fat, muscle strength, and muscle mass.
The association was slightly attenuated when adjusted for inflammatory markers, suggesting that inflammation may be a contributor.
The association between higher intramuscular fat and heart failure appeared specific to higher risk of incident heart failure with reduced ejection fraction, but not with heart failure with preserved ejection fraction.
The researchers noted that skeletal muscle is a pivotal endocrine organ in addition to the role it plays in the production of mechanical power.
They pointed out that there are differences in the biology of intermuscular and intramuscular fat deposition, and that excess intramuscular fat deposition is a result of dysregulated lipid metabolism and is associated with insulin resistance (a known risk factor for the development of heart failure), inflammation, and muscle wasting conditions.
They concluded that, in patients with heart failure, alterations in skeletal muscle function are most likely affected by multiple contributors, including inflammation, oxidative stress, and neurohormonal factors. “As these factors are also implicated in the pathogenesis of heart failure, intramuscular fat deposition may indicate a biological milieu that increases the risk of heart failure.”
New approaches to reduce heart failure risk?
In an accompanying editorial, Salvatore Carbone, PhD, Virginia Commonwealth University, Richmond, said the findings of the study are “exceptionally novel,” providing novel evidence that noncardiac body composition compartments, particularly intramuscular adipose tissue, can predict the risk for heart failure in a diverse population of older adults.
He called for further research to understand the mechanisms involved and to assess if this risk factor can be effectively modified to reduce the risk of developing heart failure.
Dr. Carbone reported that intramuscular adipose tissue can be influenced by dietary fat intake and can be worsened by accumulation of saturated fatty acids, which also contribute to insulin resistance.
He noted that saturated fatty acid–induced insulin resistance in the skeletal muscle appears to be mediated by proinflammatory pathways within the skeletal muscle itself, which can be reversed by monounsaturated fatty acids, like oleic acid, that can be found in the largest amount in food like olive oil, canola oil, and avocados, among others.
He added that sodium-glucose transporter 2 inhibitors, drugs used in the treatment of diabetes that have also been shown to prevent heart failure in individuals at risk, can also improve the composition of intramuscular adipose tissue by reducing its content of saturated fatty acids and increase the content of monosaturated fatty acids.
The study results suggest that the quality of intramuscular adipose tissue might also play an important role and could be targeted by therapeutic strategies, he commented.
Dr. Carbone concluded that “studies testing novel modalities of exercise training, intentional weight loss, diet quality improvements with and without weight loss (i.e., increase of dietary monounsaturated fatty acids, such as oleic acid), as well as pharmacological anti-inflammatory strategies should be encouraged in this population to test whether the reduction in intramuscular adipose tissue or improvements of its quality can ultimately reduce the risk for heart failure in this population.”
This research was supported by the National Institute on Aging and the National Institute of Nursing Research. Dr. Huynh and Dr. Carbone disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in a new study. The association was independent of other cardiometabolic risk factors and measures of adiposity such as body mass index.
The observation raises the possibility of new avenues of research aimed at modifying intramuscular fat levels as a strategy to reduce the risk of developing heart failure.
The study was published online in JACC: Heart Failure.
The authors, led by Kevin Huynh, MD, University of Texas Southwestern Medical Center, Dallas, explained that obesity is a known risk for heart failure, and has been incorporated into risk calculators for heart failure.
However, obesity is a complex and heterogeneous disease with substantial regional variability of adipose deposition in body tissues, they noted. For example, variability in visceral adipose tissue and subcutaneous adipose tissue has been shown to have a differential impact on both cardiovascular risk factors and clinical cardiovascular disease outcomes.
The fat deposition around and within nonadipose tissues (termed “ectopic fat”), such as skeletal muscle, is also a known risk factor for cardiovascular disease, independent of adiposity. However, the impact of peripheral skeletal muscle fat deposition on heart failure risk is not as well studied.
The researchers noted that ectopic fat in skeletal muscle can be measured through imaging and categorized as either intermuscular or intramuscular fat according to the location of muscle fat around or within skeletal muscle, respectively.
The researchers conducted the current study to characterize the association of both intermuscular and intramuscular fat deposition with heart failure risk in a large cohort of older adults.
They used data from 2,399 individuals aged 70-79 years without heart failure at baseline who participated in the Health ABC (Health, Aging and Body Composition) study. Measures of intramuscular and intermuscular fat in the thigh were determined by CT, and the participants were followed for an average of 12 years.
During the follow-up period, there were 485 incident heart failure events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with heart failure risk.
After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was significantly associated with higher risk for heart failure.
Individuals in the highest tertile of intramuscular fat had a 34% increased risk of developing heart failure, compared with those in the lowest tertile. This finding was independent of other cardiometabolic risk factors, measures of adiposity including body mass index and percent fat, muscle strength, and muscle mass.
The association was slightly attenuated when adjusted for inflammatory markers, suggesting that inflammation may be a contributor.
The association between higher intramuscular fat and heart failure appeared specific to higher risk of incident heart failure with reduced ejection fraction, but not with heart failure with preserved ejection fraction.
The researchers noted that skeletal muscle is a pivotal endocrine organ in addition to the role it plays in the production of mechanical power.
They pointed out that there are differences in the biology of intermuscular and intramuscular fat deposition, and that excess intramuscular fat deposition is a result of dysregulated lipid metabolism and is associated with insulin resistance (a known risk factor for the development of heart failure), inflammation, and muscle wasting conditions.
They concluded that, in patients with heart failure, alterations in skeletal muscle function are most likely affected by multiple contributors, including inflammation, oxidative stress, and neurohormonal factors. “As these factors are also implicated in the pathogenesis of heart failure, intramuscular fat deposition may indicate a biological milieu that increases the risk of heart failure.”
New approaches to reduce heart failure risk?
In an accompanying editorial, Salvatore Carbone, PhD, Virginia Commonwealth University, Richmond, said the findings of the study are “exceptionally novel,” providing novel evidence that noncardiac body composition compartments, particularly intramuscular adipose tissue, can predict the risk for heart failure in a diverse population of older adults.
He called for further research to understand the mechanisms involved and to assess if this risk factor can be effectively modified to reduce the risk of developing heart failure.
Dr. Carbone reported that intramuscular adipose tissue can be influenced by dietary fat intake and can be worsened by accumulation of saturated fatty acids, which also contribute to insulin resistance.
He noted that saturated fatty acid–induced insulin resistance in the skeletal muscle appears to be mediated by proinflammatory pathways within the skeletal muscle itself, which can be reversed by monounsaturated fatty acids, like oleic acid, that can be found in the largest amount in food like olive oil, canola oil, and avocados, among others.
He added that sodium-glucose transporter 2 inhibitors, drugs used in the treatment of diabetes that have also been shown to prevent heart failure in individuals at risk, can also improve the composition of intramuscular adipose tissue by reducing its content of saturated fatty acids and increase the content of monosaturated fatty acids.
The study results suggest that the quality of intramuscular adipose tissue might also play an important role and could be targeted by therapeutic strategies, he commented.
Dr. Carbone concluded that “studies testing novel modalities of exercise training, intentional weight loss, diet quality improvements with and without weight loss (i.e., increase of dietary monounsaturated fatty acids, such as oleic acid), as well as pharmacological anti-inflammatory strategies should be encouraged in this population to test whether the reduction in intramuscular adipose tissue or improvements of its quality can ultimately reduce the risk for heart failure in this population.”
This research was supported by the National Institute on Aging and the National Institute of Nursing Research. Dr. Huynh and Dr. Carbone disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
in a new study. The association was independent of other cardiometabolic risk factors and measures of adiposity such as body mass index.
The observation raises the possibility of new avenues of research aimed at modifying intramuscular fat levels as a strategy to reduce the risk of developing heart failure.
The study was published online in JACC: Heart Failure.
The authors, led by Kevin Huynh, MD, University of Texas Southwestern Medical Center, Dallas, explained that obesity is a known risk for heart failure, and has been incorporated into risk calculators for heart failure.
However, obesity is a complex and heterogeneous disease with substantial regional variability of adipose deposition in body tissues, they noted. For example, variability in visceral adipose tissue and subcutaneous adipose tissue has been shown to have a differential impact on both cardiovascular risk factors and clinical cardiovascular disease outcomes.
The fat deposition around and within nonadipose tissues (termed “ectopic fat”), such as skeletal muscle, is also a known risk factor for cardiovascular disease, independent of adiposity. However, the impact of peripheral skeletal muscle fat deposition on heart failure risk is not as well studied.
The researchers noted that ectopic fat in skeletal muscle can be measured through imaging and categorized as either intermuscular or intramuscular fat according to the location of muscle fat around or within skeletal muscle, respectively.
The researchers conducted the current study to characterize the association of both intermuscular and intramuscular fat deposition with heart failure risk in a large cohort of older adults.
They used data from 2,399 individuals aged 70-79 years without heart failure at baseline who participated in the Health ABC (Health, Aging and Body Composition) study. Measures of intramuscular and intermuscular fat in the thigh were determined by CT, and the participants were followed for an average of 12 years.
During the follow-up period, there were 485 incident heart failure events. Higher sex-specific tertiles of intramuscular and intermuscular fat were each associated with heart failure risk.
After multivariable adjustment for age, sex, race, education, blood pressure, fasting blood sugar, current smoking, prevalent coronary disease, and creatinine, higher intramuscular fat, but not intermuscular fat, was significantly associated with higher risk for heart failure.
Individuals in the highest tertile of intramuscular fat had a 34% increased risk of developing heart failure, compared with those in the lowest tertile. This finding was independent of other cardiometabolic risk factors, measures of adiposity including body mass index and percent fat, muscle strength, and muscle mass.
The association was slightly attenuated when adjusted for inflammatory markers, suggesting that inflammation may be a contributor.
The association between higher intramuscular fat and heart failure appeared specific to higher risk of incident heart failure with reduced ejection fraction, but not with heart failure with preserved ejection fraction.
The researchers noted that skeletal muscle is a pivotal endocrine organ in addition to the role it plays in the production of mechanical power.
They pointed out that there are differences in the biology of intermuscular and intramuscular fat deposition, and that excess intramuscular fat deposition is a result of dysregulated lipid metabolism and is associated with insulin resistance (a known risk factor for the development of heart failure), inflammation, and muscle wasting conditions.
They concluded that, in patients with heart failure, alterations in skeletal muscle function are most likely affected by multiple contributors, including inflammation, oxidative stress, and neurohormonal factors. “As these factors are also implicated in the pathogenesis of heart failure, intramuscular fat deposition may indicate a biological milieu that increases the risk of heart failure.”
New approaches to reduce heart failure risk?
In an accompanying editorial, Salvatore Carbone, PhD, Virginia Commonwealth University, Richmond, said the findings of the study are “exceptionally novel,” providing novel evidence that noncardiac body composition compartments, particularly intramuscular adipose tissue, can predict the risk for heart failure in a diverse population of older adults.
He called for further research to understand the mechanisms involved and to assess if this risk factor can be effectively modified to reduce the risk of developing heart failure.
Dr. Carbone reported that intramuscular adipose tissue can be influenced by dietary fat intake and can be worsened by accumulation of saturated fatty acids, which also contribute to insulin resistance.
He noted that saturated fatty acid–induced insulin resistance in the skeletal muscle appears to be mediated by proinflammatory pathways within the skeletal muscle itself, which can be reversed by monounsaturated fatty acids, like oleic acid, that can be found in the largest amount in food like olive oil, canola oil, and avocados, among others.
He added that sodium-glucose transporter 2 inhibitors, drugs used in the treatment of diabetes that have also been shown to prevent heart failure in individuals at risk, can also improve the composition of intramuscular adipose tissue by reducing its content of saturated fatty acids and increase the content of monosaturated fatty acids.
The study results suggest that the quality of intramuscular adipose tissue might also play an important role and could be targeted by therapeutic strategies, he commented.
Dr. Carbone concluded that “studies testing novel modalities of exercise training, intentional weight loss, diet quality improvements with and without weight loss (i.e., increase of dietary monounsaturated fatty acids, such as oleic acid), as well as pharmacological anti-inflammatory strategies should be encouraged in this population to test whether the reduction in intramuscular adipose tissue or improvements of its quality can ultimately reduce the risk for heart failure in this population.”
This research was supported by the National Institute on Aging and the National Institute of Nursing Research. Dr. Huynh and Dr. Carbone disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JACC: HEART FAILURE
Evidence still lacking that vitamins prevent CVD, cancer: USPSTF
There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.
However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.
These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.
“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.
“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.
“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.
Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.
“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.
The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.
“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.
On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.
However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.
“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.
But he noted that the task force did not find any significant harms from taking multivitamins.
“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.
Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.
“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
‘Any benefit likely to be small’
In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.
The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.
They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).
“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.
The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.
However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.
The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
Possible benefit for older adults?
Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.
“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”
However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.
She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.
“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.
“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”
A version of this article first appeared on Medscape.com.
There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.
However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.
These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.
“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.
“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.
“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.
Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.
“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.
The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.
“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.
On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.
However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.
“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.
But he noted that the task force did not find any significant harms from taking multivitamins.
“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.
Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.
“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
‘Any benefit likely to be small’
In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.
The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.
They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).
“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.
The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.
However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.
The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
Possible benefit for older adults?
Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.
“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”
However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.
She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.
“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.
“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”
A version of this article first appeared on Medscape.com.
There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the U.S. Preventive Services Task Force concludes.
However, there are two vitamins – vitamin E and beta-carotene – that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos.
These are the main findings of the USPSTF’s final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer. The statement was published in JAMA.
“This is essentially the same recommendation that the task force made in 2014,” USPSTF member John Wong, MD, professor of medicine at Tufts University, Boston, said in an interview.
“We recognize that over half of people in the U.S. take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer,” Dr. Wong explained.
“We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking,” he noted.
Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Dr. Wong explained.
“While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E,” he said.
The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized, controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force noted.
“Apart from beta-carotene and vitamin E, after reviewing 84 studies – including 78 randomized controlled trials – in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don’t know whether people should take vitamins or not, and we need more research,” Dr. Wong added.
On the use of a multivitamin supplement, Dr. Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.
However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.
“The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn’t really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in U.S. male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins,” Dr. Wong explained.
But he noted that the task force did not find any significant harms from taking multivitamins.
“There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn’t find sufficient evidence to be able to make a recommendation,” he said.
Asked what he would say to all the people currently taking multivitamins, Dr. Wong responded that he would advise them to have a conversation with a trusted health care professional about their particular circumstances.
“Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency,” he commented.
‘Any benefit likely to be small’
In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD; Natalie Cameron, MD; and Jeffrey Linder, MD – all from Northwestern University, Chicago – noted that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.
The editorialists pointed out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.
They gave an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5-10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).
“In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed,” they said.
The editorialists recommended that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.
However, they added that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.
The editorialists suggested that, rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.
Possible benefit for older adults?
Commenting on the USPSTF statement, JoAnn Manson, MD, chief, division of preventive medicine, Brigham and Women’s Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.
“The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing,” she said. “Although it’s easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can’t be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods.”
However, Dr. Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.
She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.
“The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality,” she noted. “Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults,” Dr. Manson said.
“Many people view multivitamins as a form of insurance, as a way to hedge their bets,” she added. “Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it’s important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day.”
A version of this article first appeared on Medscape.com.
FROM JAMA
Remnant cholesterol improves CV risk prediction
, a new study suggests.
The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.
“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.
They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.
They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.
However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.
“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.
The study was published online in the Journal of the American College of Cardiology.
The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.
“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.
They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.
They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.
The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.
For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.
During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).
Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.
Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.
Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.
When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.
In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.
The editorialists note that both fasting and nonfasting lipid values provide useful information for atherosclerotic cardiovascular disease (ASCVD) risk estimation, and elevated nonfasting remnant cholesterol appears to help identify persons at greater risk for an initial cardiovascular ischemic event.
They add that very elevated levels (above the 75th percentile) of nonfasting remnant cholesterol deserve further evaluation as a potentially valuable “modifier of ASCVD risk,” and replication of the results could move these findings forward to potentially improve prognostication and care for patients at risk for ischemic heart disease events.
An indirect measure of triglycerides
Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.
“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”
He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.
“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.
While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.
“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.
This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.
“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.
They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.
They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.
However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.
“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.
The study was published online in the Journal of the American College of Cardiology.
The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.
“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.
They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.
They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.
The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.
For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.
During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).
Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.
Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.
Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.
When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.
In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.
The editorialists note that both fasting and nonfasting lipid values provide useful information for atherosclerotic cardiovascular disease (ASCVD) risk estimation, and elevated nonfasting remnant cholesterol appears to help identify persons at greater risk for an initial cardiovascular ischemic event.
They add that very elevated levels (above the 75th percentile) of nonfasting remnant cholesterol deserve further evaluation as a potentially valuable “modifier of ASCVD risk,” and replication of the results could move these findings forward to potentially improve prognostication and care for patients at risk for ischemic heart disease events.
An indirect measure of triglycerides
Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.
“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”
He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.
“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.
While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.
“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.
This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.
A version of this article first appeared on Medscape.com.
, a new study suggests.
The study, which followed almost 42,000 Danish individuals without a history of ischemic cardiovascular disease, diabetes, or statin use for more than 10 years, found that elevated remnant cholesterol appropriately reclassified up to 40% of those who later experienced myocardial infarction and ischemic heart disease.
“The clinical implications of our study include that doctors and patients should be aware of remnant cholesterol levels to prevent future risk of MI and ischemic heart disease,” the authors conclude.
They suggest that the development of a cardiovascular risk algorithm, including remnant cholesterol together with LDL cholesterol, would help to better identify high-risk individuals who could be candidates for statins in a primary prevention setting.
They note that physicians are encouraged to evaluate non-HDL cholesterol and/or apolipoprotein B rather than LDL cholesterol and certainly not yet remnant cholesterol, possibly because of the limited availability of remnant cholesterol values in some parts of the world.
However, they point out that remnant cholesterol can be calculated with a standard lipid profile without additional cost, which is currently already the standard procedure in the greater Copenhagen area.
“This means that the use of remnant cholesterol is easy to introduce into daily clinical practice,” they say.
The study was published online in the Journal of the American College of Cardiology.
The authors, Takahito Doi, MD, Anne Langsted, MD, and Børge Nordestgaard, from Copenhagen University Hospital, Denmark, explain that remnant cholesterol is total cholesterol minus LDL-cholesterol minus HDL-cholesterol and includes the cholesterol content of the triglyceride-rich very-low-density lipoproteins, intermediate-density lipoproteins, and chylomicron remnants in the nonfasting state.
“When these particles enter the arterial wall, they are taken up by macrophages to produce foam cells, and therefore elevated remnant cholesterol likely enhance accumulation of cholesterol in the arterial wall, leading to progression of atherosclerosis and in consequence ischemic heart disease,” they note.
They point out that most guidelines for assessment of the 10-year risk of ischemic heart and atherosclerotic cardiovascular disease include levels of total and HDL cholesterol, but remnant cholesterol levels are not included.
They conducted the current study to investigate whether elevated remnant cholesterol would lead to appropriate reclassification of individuals who later experienced MI or ischemic heart disease.
The researchers analyzed data from the Copenhagen General Population Study, which recruited individuals from the White Danish general population from 2003-2015 and followed them until 2018. Information on lifestyle, health, and medication, including statin therapy, was obtained through a questionnaire, and participants underwent physical examinations and had nonfasting blood samples drawn for biochemical measurements.
For the current study, they included 41,928 individuals aged 40-100 years enrolled before 2009 without a history of ischemic cardiovascular disease, diabetes, and statin use at baseline. The median follow-up time was 12 years. Information on diagnoses of MI and ischemic heart disease was collected from the national Danish Causes of Death Registry and all hospital admissions and diagnoses entered in the national Danish Patient Registry.
During the first 10 years of follow-up there were 1,063 MIs and 1,460 ischemic heart disease events (death of ischemic heart disease, nonfatal MI, and coronary revascularization).
Results showed that in models based on conventional risk factors estimating risk of heart disease of above or below 5% in 10 years, adding remnant cholesterol at levels above the 95th percentile, appropriately reclassified 23% of individuals who had an MI and 21% of individuals who had an ischemic heart disease event.
Using remnant cholesterol levels above the 75th percentile appropriately reclassified 10% of those who had an MI and 8% of those who had an ischemic heart disease event. No events were reclassified incorrectly.
Using measurements of remnant cholesterol also improved reclassification of individuals with heart disease risk above or below 7.5% or 10% in 10 years.
When reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% of individuals with MI and 41% with ischemic heart disease events were reclassified appropriately.
In an editorial accompanying publication of the study in JACC, Peter Wilson, MD, Emory University School of Medicine, Atlanta, and Alan Remaley, MD, National Heart, Lung, and Blood Institute, say these findings rekindle interest in atherogenic nonfasting lipid measurements and emphasize an important role for elevated nonfasting remnant cholesterol as a value-added predictor of ischemic events.
The editorialists note that both fasting and nonfasting lipid values provide useful information for atherosclerotic cardiovascular disease (ASCVD) risk estimation, and elevated nonfasting remnant cholesterol appears to help identify persons at greater risk for an initial cardiovascular ischemic event.
They add that very elevated levels (above the 75th percentile) of nonfasting remnant cholesterol deserve further evaluation as a potentially valuable “modifier of ASCVD risk,” and replication of the results could move these findings forward to potentially improve prognostication and care for patients at risk for ischemic heart disease events.
An indirect measure of triglycerides
Dr. Wilson explained that remnant cholesterol is an indirect measure of triglycerides beyond LDL levels, and it is thus including a new lipid measurement in risk prediction.
“We are completely focused on LDL cholesterol,” he said. “This opens it up a bit by adding in another measure that takes into account triglycerides as well as LDL.”
He also pointed out that use of a nonfasting sample is another advantage of measuring remnant cholesterol.
“An accurate measure of LDL needs a fasting sample, which is a nuisance, whereas remnant cholesterol can be measured in a nonfasting blood sample, so it is more convenient,” Dr. Wilson said.
While this study shows this measure is helpful for risk prediction in the primary prevention population, Dr. Wilson believes remnant cholesterol could be most useful in helping to guide further medication choice in patients who are already taking statins.
“Statins mainly target LDL, but if we can also measure nonfasting triglycerides this will be helpful. It may help us select some patients who may need a different type of drug to use in addition to statins that lowers triglycerides,” he said.
This work was supported by the Global Excellence Programme, the Research Fund for the Capital Region of Denmark, the Japanese College of Cardiology Overseas Research Fellowship, and the Scandinavia Japan Sasakawa Foundation. Mr. Nordestgaard has reported consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, and Silence Therapeutics. Dr. Doi has reported talks sponsored by MSD.
A version of this article first appeared on Medscape.com.
New National Lipid Association statement on statin intolerance
The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.
The statement was published online in the Journal of Clinical Lipidology.
It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.
The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.
To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.
The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.
In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.
“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.
“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.
Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”
He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.
“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.
One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.
But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.
“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”
Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.
“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”
He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.
“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”
Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.
“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.
“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”
Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.
Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming.
Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”
“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.
He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).
A version of this article first appeared on Medscape.com.
The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.
The statement was published online in the Journal of Clinical Lipidology.
It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.
The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.
To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.
The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.
In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.
“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.
“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.
Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”
He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.
“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.
One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.
But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.
“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”
Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.
“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”
He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.
“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”
Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.
“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.
“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”
Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.
Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming.
Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”
“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.
He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).
A version of this article first appeared on Medscape.com.
The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.
The statement was published online in the Journal of Clinical Lipidology.
It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.
The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.
To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.
The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.
In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.
“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.
“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.
Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”
He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.
“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.
One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.
But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.
“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”
Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.
“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”
He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.
“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”
Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.
“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.
“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”
Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.
Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming.
Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”
“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.
He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL LIPIDOLOGY
Emergency angiography for cardiac arrest without ST elevation?
Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.
In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.
The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.
But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.
“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”
The EMERGE study was published online in JAMA Cardiology.
In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.
In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.
But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).
The EMERGE trial was conducted in this latter group without ST elevation.
For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.
The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).
There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.
Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.
However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.
Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.
“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.
In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.
“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.
Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.
“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.
In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.
The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.
But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.
“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”
The EMERGE study was published online in JAMA Cardiology.
In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.
In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.
But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).
The EMERGE trial was conducted in this latter group without ST elevation.
For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.
The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).
There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.
Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.
However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.
Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.
“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.
In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.
“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.
Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.
“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients successfully resuscitated after an out-of-hospital cardiac arrest who did not have ST-segment elevation on their electrocardiogram did not benefit from emergency coronary angiography in a new randomized clinical trial.
In the EMERGE trial, a strategy of emergency coronary angiography was not found to be better than a strategy of delayed coronary angiography with respect to the 180-day survival rate with no or minimal neurologic sequelae.
The authors note that, although the study was underpowered, the results are consistent with previously published studies and do not support routine emergency coronary angiography in survivors of out-of-hospital cardiac arrest without ST elevation.
But senior author, Christian Spaulding, MD, PhD, European Hospital Georges Pompidou, Paris, believes some such patients may still benefit from emergency angiography.
“Most patients who have been resuscitated after out of hospital cardiac arrest will have neurological damage, which will be the primary cause of death,” Dr. Spaulding told this news organization. “It will not make any difference to these patients if they have a coronary lesion treated. So, going forward, I think we need to look for patients who are likely not to have a high degree of neurological damage and who could still benefit from early angiography.”
The EMERGE study was published online in JAMA Cardiology.
In patients who have suffered an out-of-hospital cardiac arrest with no obvious noncardiac cause such as trauma, it is believed that the cardiac arrest is caused by coronary occlusions, and emergency angiography may be able to improve survival in these patients, Dr. Spaulding explained.
In about one-third of such patients, the ECG before hospitalization shows ST elevation, and in this group, there is a high probability (around 70%-80%) that there is going to be a coronary occlusion, so these patients are usually taken directly to emergency angiography.
But, in the other two-thirds of patients, there is no ST elevation on the ECG, and in these patients the chances of finding a coronary occlusion are lower (around 25%-35%).
The EMERGE trial was conducted in this latter group without ST elevation.
For the study, which was conducted in 22 French centers, 279 such patients (mean age, 64 years) were randomized to either emergency or delayed (48-96 hours) coronary angiography. The mean time delay between randomization and coronary angiography was 0.6 hours in the emergency group and 55.1 hours in the delayed group.
The primary outcome was the 180-day survival rate with minimal neurological damage, defined as Cerebral Performance Category of 2 or less. This occurred in 34.1% of the emergency angiography group and 30.7% of the delayed angiography group (hazard ratio, 0.87; 95% confidence interval, 0.65-1.15; P = .32).
There was also no difference in the overall survival rate at 180 days (36.2% vs. 33.3%; HR, 0.86; P = .31) and in secondary outcomes between the two groups.
Dr. Spaulding noted that three other randomized trials in a similar patient population have all shown similar results, with no difference in survival found between patients who have emergency coronary angiography as soon as they are admitted to hospital and those in whom angiography was not performed until a couple of days later.
However, several registry studies in a total of more than 6,000 patients have suggested a benefit of immediate angiography in these patients. “So, there is some disconnect here,” he said.
Dr. Spaulding believes the reason for this disconnect may be that the registry studies may have included patients with less neurological damage so more likely to survive and to benefit from having coronary lesions treated promptly.
“Paramedics sometimes make a judgment on which patients may have minimal neurological damage, and this may affect the choice of hospital a patient is taken to, and then the emergency department doctor may again assess whether a patient should go for immediate angiography or not. So, patients in these registry studies who received emergency angiography were likely already preselected to some extent,” he suggested.
In contrast, the randomized trials have accepted all patients, so there were probably more with neurological damage. “In our trial, almost 70% of patients were in asystole. These are the ones who [are] the most likely to have neurological damage,” he pointed out.
“Because there was such a striking difference in the registry studies, I think there is a group of patients [who] will benefit from immediate emergency coronary angiography, but we have to work out how to select these patients,” he commented.
Dr. Spaulding noted that a recent registry study published in JACC: Cardiovascular Interventions used a score known as MIRACLE2, (which takes into account various factors including age of patient and type of rhythm on ECG) and the degree of cardiogenic shock on arrival at hospital as measured by the SCAI shock score to define a potential cohort of patients at low risk for neurologic injury who benefit most from immediate coronary angiography.
“In my practice at present, I would advise the emergency team that a young patient who had had resuscitation started quickly, had been defibrillated early, and got to hospital quickly should go for an immediate coronary angiogram. It can’t do any harm, and there may be a benefit in such patients,” Dr. Spaulding added.The EMERGE study was supported in part by Assistance Publique–Hôpitaux de Paris and the French Ministry of Health, through the national Programme Hospitalier de Recherche Clinique. Dr. Spaulding reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘Sit less, move more’ to reduce stroke risk
in a population-based study of middle aged and older adults.
The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.
“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”
Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.
“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.
“Our message is basically to sit less and move more,” he added.
The study was published online in JAMA Network Open.
The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.
The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.
Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.
Results showed that increased levels of physical activity were associated with reduced risk of stroke.
For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.
In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).
Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.
In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.
Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”
But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
Long bouts of sedentary time are harmful
The study also showed that sedentary time was associated with a higher risk for stroke.
The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.
They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.
“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.
They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).
“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.
“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.
This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.
A version of this article first appeared on Medscape.com.
in a population-based study of middle aged and older adults.
The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.
“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”
Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.
“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.
“Our message is basically to sit less and move more,” he added.
The study was published online in JAMA Network Open.
The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.
The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.
Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.
Results showed that increased levels of physical activity were associated with reduced risk of stroke.
For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.
In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).
Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.
In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.
Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”
But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
Long bouts of sedentary time are harmful
The study also showed that sedentary time was associated with a higher risk for stroke.
The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.
They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.
“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.
They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).
“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.
“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.
This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.
A version of this article first appeared on Medscape.com.
in a population-based study of middle aged and older adults.
The study also found relatively short periods of moderate to vigorous exercise were associated with reduced stroke risk.
“Our results suggest there are a number of ways to reduce stroke risk simply by moving about,” said lead author Steven P. Hooker, PhD, San Diego State University. “This could be with short periods of moderate to vigorous activity each day, longer periods of light activity, or just sedentary for shorter periods of time. All these things can make a difference.”
Dr. Hooker explained that, while it has been found previously that moderate to vigorous exercise reduces stroke risk, this study gives more information on light-intensity activities and sedentary behavior and the risk of stroke.
“Our results suggest that you don’t have to be a chronic exerciser to reduce stroke risk. Replacing sedentary time with light-intensity activity will be beneficial. Just go for a short walk, get up from your desk and move around the house at regular intervals. That can help to reduce stroke risk,” Dr. Hooker said.
“Our message is basically to sit less and move more,” he added.
The study was published online in JAMA Network Open.
The study involved 7,607 U.S. individuals without a history of stroke, with oversampling from the southeastern “Stroke Belt,” who were participating in the REGARDS cohort study.
The participants wore an accelerometer to measure physical activity and sedentary behavior for 7 consecutive days. The mean age of the individuals was 63 years; 54% were female, 32% were Black.
Over a mean follow-up of 7.4 years, 286 incident stroke cases occurred.
Results showed that increased levels of physical activity were associated with reduced risk of stroke.
For moderate to vigorous activity, compared with participants in the lowest tertile, those in the highest tertile of total daily time in moderate to vigorous activity had a 43% lower risk of stroke.
In the current study, the amount of moderate to vigorous activity associated with a significant reduction in stroke risk was approximately 25 minutes per day (3 hours per week).
Dr. Hooker noted that moderate to vigorous activity included things such as brisk walking, jogging, bike riding, swimming, or playing tennis or soccer. “Doing such activities for just 25 minutes per day reduced risk of stroke by 43%. This is very doable. Just commuting to work by bicycle would cover you here,” he said.
In terms of light-intensity activity, individuals who did 4-5 hours of light activities each day had a 26% reduced risk for first stroke, compared with those doing less than 3 hours of such light activities.
Dr. Hooker explained that examples of light activity included household chores, such as vacuuming, washing dishes, or going for a gentle stroll. “These activities do not require heaving breathing, increased heart rate or breaking into a sweat. They are activities of daily living and relatively easy to engage in.”
But he pointed out that the 4-5 hours of light activity every day linked to a reduction in stroke risk may be more difficult to achieve than the 25 minutes of moderate to vigorous activity, saying: “You have to have some intentionality here.”
Long bouts of sedentary time are harmful
The study also showed that sedentary time was associated with a higher risk for stroke.
The authors noted that time spent in sedentary behavior is of interest because most adults spend most of their awake time being physically inactive.
They report that participants in the highest tertile of sedentary time (more than 13 hours/day) exhibited a 44% increase in risk of stroke, compared with those in the lowest tertile (less than 11 hours/day), and the association remained significant when adjusted for several covariates, including moderate to vigorous activity.
“Even when controlling for the amount of other physical activity, sedentary behavior is still highly associated with risk of stroke. So even if you are active, long bouts of sedentary behavior are harmful,” Dr. Hooker commented.
They also found that longer bouts of sedentary time (more than 17 minutes at a time) were associated with a 54% higher risk of stroke than shorter bouts (less than 8 minutes).
“This suggests that breaking up periods of sedentary behavior into shorter bouts would be beneficial,” Dr. Hooker said.
“If you are going to spend the evening on the couch watching television, try to stand up and walk around every few minutes. Same for if you are sitting at a computer all day – try having a standing workstation, or at least take regular breaks to walk around,” he added.
This research was supported by grants from the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. Additional funding was provided by an unrestricted grant from the Coca-Cola Company. The authors report no disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN