Lipid Disorders

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

The scientific statement was published online in the Journal of the American Heart Association.
 

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

The scientific statement was published online in the Journal of the American Heart Association.
 

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

People who are socially isolated or lonely have an increased risk for myocardial infarction, stroke, and death, independent of other factors, the American Heart Association concludes in a new scientific statement.

More than 4 decades of research have “clearly demonstrated that social isolation and loneliness are both associated with adverse health outcomes,” writing group chair Crystal Wiley Cené, MD, University of California San Diego Health, said in a news release.

“Given the prevalence of social disconnectedness across the United States, the public health impact is quite significant,” Dr. Cené added.

The writing group says more research is needed to develop, implement, and test interventions to improve cardiovascular (CV) and brain health in people who are socially isolated or lonely.

The scientific statement was published online in the Journal of the American Heart Association.
 

Common and potentially deadly

Social isolation is defined as having infrequent in-person contact with people and loneliness is when a person feels he or she is alone or has less connection with others than desired.

It’s estimated that one-quarter of community-dwelling Americans 65 years and older are socially isolated, with even more experiencing loneliness.

The problem is not limited to older adults, however. Research suggests that younger adults also experience social isolation and loneliness, which might be attributed to more social media use and less frequent in-person activities.

Dr. Cené and colleagues reviewed observational and intervention research on social isolation published through July 2021 to examine the impact of social isolation and loneliness on CV and brain health.

The evidence is most consistent for a direct association between social isolation, loneliness, and death from coronary heart disease (CHD) and stroke, they reported.

For example, one meta-analysis of 19 studies showed that social isolation and loneliness increase the risk for CHD by 29%; most of these studies focused on acute MI and/or CHD death as the measure of CHD.

A meta-analysis of eight longitudinal observational studies showed social isolation and loneliness were associated with a 32% increased risk for stroke, after adjustment for age, sex, and socioeconomic status.

The literature also suggests social isolation and loneliness are associated with worse prognoses in adults with existing CHD or history of stroke.

One systematic review showed that socially isolated people with CHD had a two- to threefold increase in illness and death over 6 years, independent of cardiac risk factors.

Other research suggests that socially isolated adults with three or fewer social contacts per month have a 40% increased risk for recurrent stroke or MI.

There are fewer and less robust data on the association between social isolation and loneliness with heart failure (HF), dementia, and cognitive impairment, the writing group noted.

It’s also unclear whether actually being isolated (social isolation) or feeling isolated (loneliness) matters most for cardiovascular and brain health, because only a few studies have examined both in the same sample, they pointed out.

However, a study published in Neurology in June showed that older adults who reported feeling socially isolated had worse cognitive function at baseline than did those who did not report social isolation, and were 26% more likely to have dementia at follow-up, as reported by this news organization.
 

Urgent need for interventions

“There is an urgent need to develop, implement, and evaluate programs and strategies to reduce the negative effects of social isolation and loneliness on cardiovascular and brain health, particularly for at-risk populations,” Dr. Cené said in the news release. 

She encourages clinicians to ask patients about their social life and whether they are satisfied with their level of interactions with friends and family, and to be prepared to refer patients who are socially isolated or lonely, especially those with a history of CHD or stroke, to community resources to help them connect with others.

Fitness programs and recreational activities at senior centers, as well as interventions that address negative thoughts of self-worth and other negative thinking, have shown promise in reducing isolation and loneliness, the writing group said.

This scientific statement was prepared by the volunteer writing group on behalf of the AHA Social Determinants of Health Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Quality of Care and Outcomes Research; the Prevention Science Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing; the Council on Arteriosclerosis, Thrombosis, and Vascular Biology; and the Stroke Council.

This research had no commercial funding. Members of the writing group have disclosed no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Lipoprotein(a) has long been thought to be a potential marker of aortic valve disease, and the population-based Rotterdam Study in the Netherlands has reported that Lp(a) has a strong association with new-onset aortic valve calcium (AVC), but not necessarily with progression of aortic valve disease.

Reporting in the European Heart Journal, the study authors analyzed data on 922 participants in the Rotterdam Study whose Lp(a) was measured along with a computed tomography scan upon enrollment, followed by CT scan 14 years later. At baseline, 702 participants didn’t have AVC, but the follow-up scan identified new-onset AVC in 415 (59.1%).

The investigators found an association between Lp(a) concentration and baseline AVC, with an odds ratio of 1.43 for each 50 mg/dL higher Lp(a) (95% confidence interval, 1.15-1.79), as well as new-onset AVC, with an OR of 1.30 for each 50 mg/dL increase in Lp(a) (95% CI, 1.02-1.65). However, the study found no association between rising Lp(a) levels and AVC progression; it found only an association between baseline AVC score and progression (P < .001).
 

‘Trigger’ for calcification but not progression

“This suggests that Lp(a) is an important trigger in the initiation of aortic valve calcification, but once the valve is calcified, disease progression may be primarily driven by other factors such as the baseline calcium burden of the valve and likely other unknown factors,” senior study author Daniel Bos, MD, PhD, said in e-mailed comments.

Dr. Bos and coauthors claim this is the first study to show that even minor AVC progresses independently of Lp(a).

“There are previous studies that showed a possible relationship between Lp(a) [and] progression of aortic valve calcium,” he said. “Our study suggests that the most meaningful benefit of Lp(a) lowering may actually be prior to the onset of aortic valve calcification.”

While no treatments have been approved for lowering Lp(a), the study findings could be meaningful if trials, including the ongoing phase 3 Lp(a) HORIZON trial of the investigational antisense agent pelacarsen (NCT04023552), show promising results, Dr. Bos said. Citing Lp(a) HORIZON, he said, “If the study shows Lp(a) lowering leads to a reduction in incident cardiovascular disease, similar strategies may be applied to prevent, rather than slow down, progression of aortic valve calcification.”

Dr. Bos called the Rotterdam Study results “an important first pointer into that direction.” He added, “We will need randomized trials to provide a definitive answer to the question whether Lp(a) lowering may prevent aortic valve calcium.”

Focus on AVC is study ‘weakness’

The study findings raise a key question for clinical trials of investigative Lp(a)-lowering therapies as well as how to use those therapies to treat aortic valve disease, said Christie Ballantyne, MD, chief of cardiology at Baylor College of Medicine in Houston.

The findings could be “problematic” for these clinical trials, he said. “This study is just looking at calcium progression,” Dr. Ballantyne noted. “What we want to know about clinically is the progression to aortic stenosis, and then in particular to progression from mild disease to moderate or severe disease, because once you get into more severe disease, one has to do an intervention with either surgery or TAVR [transcatheter aortic valve replacement].”

He considered the study’s focus on AVC rather than aortic valve function a weakness and noted that only 14 study participants had TAVR. “We’re going to need much bigger numbers to look into this question of progression, including progression to severe diseases,” he said.

However, the Rotterdam Study showed the importance of CT in evaluating AVC, which can easily be done in other trials to further explore the association between Lp(a) and AVC, Dr. Ballantyne said.

Dr. Bos has no relevant disclosures. Study coauthors disclosed relationships with Amgen, Sanofi, Reservlogix, Athera, Experio, Novartis and Ionis Pharmaceuticals. Dr. Ballantyne disclosed relationships with Amgen and Novartis.

Lipoprotein(a) has long been thought to be a potential marker of aortic valve disease, and the population-based Rotterdam Study in the Netherlands has reported that Lp(a) has a strong association with new-onset aortic valve calcium (AVC), but not necessarily with progression of aortic valve disease.

Reporting in the European Heart Journal, the study authors analyzed data on 922 participants in the Rotterdam Study whose Lp(a) was measured along with a computed tomography scan upon enrollment, followed by CT scan 14 years later. At baseline, 702 participants didn’t have AVC, but the follow-up scan identified new-onset AVC in 415 (59.1%).

The investigators found an association between Lp(a) concentration and baseline AVC, with an odds ratio of 1.43 for each 50 mg/dL higher Lp(a) (95% confidence interval, 1.15-1.79), as well as new-onset AVC, with an OR of 1.30 for each 50 mg/dL increase in Lp(a) (95% CI, 1.02-1.65). However, the study found no association between rising Lp(a) levels and AVC progression; it found only an association between baseline AVC score and progression (P < .001).
 

‘Trigger’ for calcification but not progression

“This suggests that Lp(a) is an important trigger in the initiation of aortic valve calcification, but once the valve is calcified, disease progression may be primarily driven by other factors such as the baseline calcium burden of the valve and likely other unknown factors,” senior study author Daniel Bos, MD, PhD, said in e-mailed comments.

Dr. Bos and coauthors claim this is the first study to show that even minor AVC progresses independently of Lp(a).

“There are previous studies that showed a possible relationship between Lp(a) [and] progression of aortic valve calcium,” he said. “Our study suggests that the most meaningful benefit of Lp(a) lowering may actually be prior to the onset of aortic valve calcification.”

While no treatments have been approved for lowering Lp(a), the study findings could be meaningful if trials, including the ongoing phase 3 Lp(a) HORIZON trial of the investigational antisense agent pelacarsen (NCT04023552), show promising results, Dr. Bos said. Citing Lp(a) HORIZON, he said, “If the study shows Lp(a) lowering leads to a reduction in incident cardiovascular disease, similar strategies may be applied to prevent, rather than slow down, progression of aortic valve calcification.”

Dr. Bos called the Rotterdam Study results “an important first pointer into that direction.” He added, “We will need randomized trials to provide a definitive answer to the question whether Lp(a) lowering may prevent aortic valve calcium.”

Focus on AVC is study ‘weakness’

The study findings raise a key question for clinical trials of investigative Lp(a)-lowering therapies as well as how to use those therapies to treat aortic valve disease, said Christie Ballantyne, MD, chief of cardiology at Baylor College of Medicine in Houston.

The findings could be “problematic” for these clinical trials, he said. “This study is just looking at calcium progression,” Dr. Ballantyne noted. “What we want to know about clinically is the progression to aortic stenosis, and then in particular to progression from mild disease to moderate or severe disease, because once you get into more severe disease, one has to do an intervention with either surgery or TAVR [transcatheter aortic valve replacement].”

He considered the study’s focus on AVC rather than aortic valve function a weakness and noted that only 14 study participants had TAVR. “We’re going to need much bigger numbers to look into this question of progression, including progression to severe diseases,” he said.

However, the Rotterdam Study showed the importance of CT in evaluating AVC, which can easily be done in other trials to further explore the association between Lp(a) and AVC, Dr. Ballantyne said.

Dr. Bos has no relevant disclosures. Study coauthors disclosed relationships with Amgen, Sanofi, Reservlogix, Athera, Experio, Novartis and Ionis Pharmaceuticals. Dr. Ballantyne disclosed relationships with Amgen and Novartis.

Lipoprotein(a) has long been thought to be a potential marker of aortic valve disease, and the population-based Rotterdam Study in the Netherlands has reported that Lp(a) has a strong association with new-onset aortic valve calcium (AVC), but not necessarily with progression of aortic valve disease.

Reporting in the European Heart Journal, the study authors analyzed data on 922 participants in the Rotterdam Study whose Lp(a) was measured along with a computed tomography scan upon enrollment, followed by CT scan 14 years later. At baseline, 702 participants didn’t have AVC, but the follow-up scan identified new-onset AVC in 415 (59.1%).

The investigators found an association between Lp(a) concentration and baseline AVC, with an odds ratio of 1.43 for each 50 mg/dL higher Lp(a) (95% confidence interval, 1.15-1.79), as well as new-onset AVC, with an OR of 1.30 for each 50 mg/dL increase in Lp(a) (95% CI, 1.02-1.65). However, the study found no association between rising Lp(a) levels and AVC progression; it found only an association between baseline AVC score and progression (P < .001).
 

‘Trigger’ for calcification but not progression

“This suggests that Lp(a) is an important trigger in the initiation of aortic valve calcification, but once the valve is calcified, disease progression may be primarily driven by other factors such as the baseline calcium burden of the valve and likely other unknown factors,” senior study author Daniel Bos, MD, PhD, said in e-mailed comments.

Dr. Bos and coauthors claim this is the first study to show that even minor AVC progresses independently of Lp(a).

“There are previous studies that showed a possible relationship between Lp(a) [and] progression of aortic valve calcium,” he said. “Our study suggests that the most meaningful benefit of Lp(a) lowering may actually be prior to the onset of aortic valve calcification.”

While no treatments have been approved for lowering Lp(a), the study findings could be meaningful if trials, including the ongoing phase 3 Lp(a) HORIZON trial of the investigational antisense agent pelacarsen (NCT04023552), show promising results, Dr. Bos said. Citing Lp(a) HORIZON, he said, “If the study shows Lp(a) lowering leads to a reduction in incident cardiovascular disease, similar strategies may be applied to prevent, rather than slow down, progression of aortic valve calcification.”

Dr. Bos called the Rotterdam Study results “an important first pointer into that direction.” He added, “We will need randomized trials to provide a definitive answer to the question whether Lp(a) lowering may prevent aortic valve calcium.”

Focus on AVC is study ‘weakness’

The study findings raise a key question for clinical trials of investigative Lp(a)-lowering therapies as well as how to use those therapies to treat aortic valve disease, said Christie Ballantyne, MD, chief of cardiology at Baylor College of Medicine in Houston.

The findings could be “problematic” for these clinical trials, he said. “This study is just looking at calcium progression,” Dr. Ballantyne noted. “What we want to know about clinically is the progression to aortic stenosis, and then in particular to progression from mild disease to moderate or severe disease, because once you get into more severe disease, one has to do an intervention with either surgery or TAVR [transcatheter aortic valve replacement].”

He considered the study’s focus on AVC rather than aortic valve function a weakness and noted that only 14 study participants had TAVR. “We’re going to need much bigger numbers to look into this question of progression, including progression to severe diseases,” he said.

However, the Rotterdam Study showed the importance of CT in evaluating AVC, which can easily be done in other trials to further explore the association between Lp(a) and AVC, Dr. Ballantyne said.

Dr. Bos has no relevant disclosures. Study coauthors disclosed relationships with Amgen, Sanofi, Reservlogix, Athera, Experio, Novartis and Ionis Pharmaceuticals. Dr. Ballantyne disclosed relationships with Amgen and Novartis.

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

A version of this article first appeared on Medscape.com.

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

A version of this article first appeared on Medscape.com.

More patients with established atherosclerotic cardiovascular disease (ASCVD) achieved a low-density lipoprotein (LDL) cholesterol of less than 70 mg/dL, and fewer discontinued treatment with ezetimibe plus a moderate-dose statin, than did those on high-intensity statin monotherapy, a noninferiority trial shows.

While it’s now established that drug combinations can achieve better efficacy with lower risks than high-dose monotherapy, the study is the first to show the benefits of the strategy for ASCVD in a randomized trial with long-term follow-up.

The primary endpoint – 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke – occurred in about 9% of patients in each group, showing non-inferiority.

Furthermore, the authors suggest that ezetimibe combination therapy be considered earlier in the treatment of those at high risk of adverse events, rather than doubling the statin dose.

The study was published online  in The Lancet.
 

Less intolerance, less discontinuations

The open-label study, dubbed RACING, randomized 3,780 patients with ASCVD to receive moderate-intensity rosuvastatin 10 mg plus ezetimibe 10 mg or high-intensity 20 mg rosuvastatin monotherapy. Participants’ average age was 64 and 75% were men.

The primary endpoint occurred in 9.1% of patients in the combination therapy group and 9.9% in the high-intensity monotherapy group. The absolute between-group difference was −0.78% (90% confidence interval [CI], −2.39 to 0.83), well below the 2% noninferiority margin.

In the combination therapy group, LDL cholesterol concentrations of less than 70 mg/dL were achieved in 73% of patients at 1 year, 75% at 2 years, and 72% at 3 years. By contrast, in the monotherapy group, the lower concentrations were seen in 55% at 1 year, 60% at 2 years, and 58% at 3 years.

Further, a post hoc analysis showed LDL concentrations of less than 55 mg/dL at 1, 2, and 3 years in 42%, 45%, and 42% of patients in the combination therapy group versus 25%, 29%, and 25% of those in the high-intensity statin monotherapy group.

Eighty-eight patients (4.8%) on combination therapy discontinued medication or received a dose reduction, versus 150 patients (8.2%) on monotherapy.

Rates of myonecrosis were similar in the combination therapy and high-intensity statin groups (11 vs. 13), whereas myalgia was more common with high-intensity statins (29 vs. 17). The open-label design could have led to bias in reporting of patient symptoms, the authors noted. All clinical events, however, were adjudicated by an independent committee masked to treatment assignment.

There might be “some level of difference” when extending the findings to other populations because the trial involved only Koreans, coauthor Myeong-Ki Hong, MD, Yonsei University, Seoul, South Korea, acknowledged in response to a query from this news organization. He thinks the findings can be applied broadly nonetheless, and his team is currently investigating whether certain patients might benefit more than others from the combination.
 

Various options for patients

“The field of hypertension changed [its] guidelines almost 20 years ago to consider the initial use of combination therapy in hard-to-treat patients,” Christie Mitchell Ballantyne, MD, Baylor College of Medicine, Houston, said in an interview. He coauthored an accompanying editorial with Baylor colleague Layla A. Abushamat, MD.

“We now have enough evidence of the efficacy and safety of combination therapy to consider early initiation of this approach in patients with challenging lipid disorders who are at increased risk of ASCVD events,” affirmed Dr. Ballantyne.

“This study reinforces important principles in the management and secondary prevention of cardiovascular disease, namely that LDL reduction and associated risk reduction can be achieved in various ways,” said Daniel Muñoz, MD, MPA, executive medical director of the Vanderbilt Heart & Vascular Institute, Vanderbilt University Medical Center, Nashville, Tenn.

However, he noted, “The high-intensity statin dose used as a comparator in this study was rosuvastatin 20 mg. In clinical practice, we often target maximally aggressive reduction of LDL via higher doses – that is, rosuvastatin 40 mg or atorvastatin 80 mg.”

The bottom line, said Dr. Muñoz, who was not involved in the study: “There are different ways to achieve LDL-lowering and associated risk reduction in patients with CVD. For patients who warrant but might not tolerate high-intensity statin therapy, this study supports the use of a moderate-intensity statin in combination with ezetimibe.”

The study was funded by Hanmi Pharmaceutical, Seoul, South Korea. One study coauthor received an institutional research grant from the company. No other authors reported relevant financial relationships, nor did Dr. Ballantyne, Dr. Abushamat, or Dr. Muñoz.

A version of this article first appeared on Medscape.com.

For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.

But a new study published  in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.

“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.

M. Alexander Otto/MDedge News

Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.

The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.

Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.

Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.

At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.

“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.

At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.

The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,

Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.

Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.

“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.

“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”

Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.

But a new study published  in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.

“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.

M. Alexander Otto/MDedge News

Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.

The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.

Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.

Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.

At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.

“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.

At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.

The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,

Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.

Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.

“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.

“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”

Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.

But a new study published  in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.

“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.

M. Alexander Otto/MDedge News

Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.

The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.

Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.

Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.

At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.

“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.

At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.

The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,

Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.

Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.

“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.

“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”

Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.

A version of this article first appeared on Medscape.com.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

Adding to a growing body of evidence that elevated remnant cholesterol (remnant-C) provides additional and independent risk prediction for major cardiovascular events (MACE), a new analysis has this shown this biomarker has prognostic value specifically in patients with type 2 diabetes (T2D).

In a post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, each standard-deviation increase in remnant-C was associated with a 7% increased risk in MACE (P = .004) after adjustment for several risk factors including other cholesterol values.

“In type 2 diabetes, remnant-C levels are associated with MACE regardless of LDL-C,” reported a team of investigators led by Liyao Fu, MD, Second Xiangya Hospital of Central South University, Changsha, China .

Remnant-C is one component of triglyceride-rich lipoproteins. Within triglyceride-rich lipoproteins, remnant-C has become a major focus of efforts to explain cardiovascular (CV) residual risk, according to the investigators.

Residual risk is a term used to explain why cardiovascular events occur after all known modifiable factors, such as LDL cholesterol (LDL-C), are controlled.

“Our primary findings indicate that baseline estimated remnant-C levels were associated with MACE regardless of clinical phenotypes, lifestyle confounders relative to CV risk, and lipid-lowering treatment,” said the authors of the analysis.

In the post hoc analysis of the ACCORD trial, which evaluated the effects of intensive glucose lowering in T2D more than 10 years ago, there were data on remnant-C over a median of 8.8 years of follow-up in 9,650 T2D patients. Over this period, 1,815 (17.8%) developed MACE.

Multiple analyses support prognostic value of remnant-C

In addition to the 7% rise in MACE for each standard-deviation increase in remnant-C when calculated as a continuous variable, other analyses told the same story.

This included an assessment by remnant-C tertiles. Not only was there a significant trend (P < .001) for greater risk with each higher baseline tertile of remnant-C, those in the highest tertile had a 38% greater risk of MACE relative to those in the lowest tertile (hazard ratio, 1.38; P < .001) after adjustment for confounders.

The same pattern was seen for several components of MACE, such as CV death and nonfatal myocardial infarction, when remnant-C tertiles were compared.

Visit-to-visit variability in remnant-C over the course of follow-up was also associated with greater risk of MACE. In logarithmic calculations, the risk of MACE climbed about 40% across all three models of risk adjustment. These models included adjustments for different sets of confounders, such as sex, age, blood pressure, CV disease history, and glucose levels. On an unadjusted basis, the risk was increased about 50% (HR, 1.52; P < .001).

For visit-to-visit variability in remnant-C, the greatest effect was on risk of nonfatal MI across models. In model 3, for example, which adjusted for the most confounders, the risk was nearly doubled (HR, 1.92; P < .001). In contrast, there did not appear to be a link between visit-to-visit variability and nonfatal stroke.

In a discordant analysis that was conducted to examine the relative risk of remnant-C independent of LDL-C, those who had a remnant-C level of at least 31 mg/dL were found to have a higher risk of MACE regardless of LDL-C level. Yet, the risk was higher if both remnant-C and LDL-C were elevated. For example, the risk was increased 22% for those with LDL-C at or below 100 mg/dL and remnant-C levels of at least 31 mg/dL (HR, 1.22; P = .015) but climbed to 37% for those with LDL-C above 100 mg/dL if remnant-C was at least 31 mg/dL (HR, 1.38; P = .007).
 

Remnant-C shows prognostic value in other risk groups

Although this study suggests an important prognostic value for remnant-C in T2D, there are numerous studies suggesting that it has prognostic value in other risk groups, such as those with a history of CV disease. This includes a study published earlier this year with 10 years of follow-up in 41,928 patients in Denmark. When combined with other risk factors, remnant-C substantially improved the accuracy of risk of events over time.

The investigators from this previous study, like the new study in patients with T2D, predict that remnant-C will be eventually included in guidelines.

According to Shi Tai, MD, a coauthor of the T2D study, remnant-C “may allow for the development of specific preventive and therapeutic approaches” to CV risk in patients with T2D.

T2D patients “with elevated plasma remnant-C levels represent a special population that deserves more attention regarding residual risk,” said Dr. Tai of the department of cardiovascular medicine at the Hospital of South Central China.
 

Great interest, but ready for guidelines?

This is an important direction of ongoing research, according to Christie M. Ballantyne, MD, professor of medicine, Baylor College of Medicine, Houston.

“There is a great deal of interest from both clinicians and trialists to find a simple way to identify patients with high residual risk who are on statin therapy,” he said. He thinks remnant-C has promise in this regard.

“Remnant-C is not in current guidelines,” he said in an interview, but he suggested that there is now a substantial body of evidence to suggest that it might be added if validated in further studies.

“Remnant-C is easy to calculate and may be helpful in practice now to identify patients who need more aggressive therapy to reduce risk and may be useful to identify patients for clinical trials who will benefit from new therapies that are in development,” he said.

However, the clinical relevance of therapies addressed at triglyceride-rich lipoproteins in general or their components, including triglycerides or remnant-C, has never been demonstrated, pointed out Peter W.F. Wilson, MD, PhD.

“Higher fasting or nonfasting triglyceride levels or their surrogates have been shown to be associated with increased risk for cardiovascular disease events in observational studies, but the importance of such measurements in persons already treated with very aggressive LDL-C lowering therapy is not known,” commented Dr. Wilson, director of epidemiology and genomic medicine, Emory School of Medicine, Atlanta.

Dr. Wilson was the coauthor of an editorial that accompanied the previously published Danish study of remnant-C. In his editorial, he suggested that remnant-C has promise for better understanding residual risk, but when contacted about these latest data he emphasized a lack of support so far for clinical relevance.

“Unfortunately, clinical trials have generally not shown that triglyceride lowering [to favorably alter remnant-C] in this situation favorably affects the risk of CV disease events,” he said in an interview. This does not preclude remnant-C as a targetable risk factor, but these data are needed.

Dr. Fu, Dr. Tai, and Dr. Wilson report no potential conflicts of interest. Dr. Ballantyne has financial relationships with more than 25 pharmaceutical companies, including several that produce products employed for the treatment of lipid abnormalities.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

The more components of metabolic syndrome a person has in midlife seems to raise their risk of dementia, although that relationship seems to go away after age 70, a post hoc analysis of data from a major European cohort study has found.

A team of European researchers reported online in the journal Diabetes Care that the follow-up of the Whitehall II cohort study, a study of more than 10,000 civil servants in London that was established in the late 1980s, also found that cardiovascular disease (CVD) may only partially contribute to the risk of dementia in study participants.

They found that each additional metabolic syndrome component before age 60 years was linked to a 13% rise in the risk of dementia (hazard ratio, 1.13; 95% confidence interval [CI], 1.05-1.23) and, from age 60 to 70, the risk rose 8% (HR, 1.08; 95% CI, 1.00-1.16). However, in people aged 70 years and older, the relationship wasn’t statistically significant (HR, 1.04; 95% CI, 0.96-1.13]).

The study used “the latest harmonized definition” of metabolic syndrome; that is, participants were classified as having metabolic syndrome if they had three or more of the five components. As lead author Marcos D. Machado-Fragua, PhD, noted in an email interview, those components are abdominal obesity, high triglycerides, low HDL cholesterol levels, high blood pressure, and high fasting glucose.

“Our research question was on the association between metabolic syndrome and late-life dementia. We found that the presence of one metabolic syndrome component and the presence of metabolic risk before age 60, but not after, is associated with higher risk of dementia,” said Dr. Machado-Fragua, a post-doctoral researcher at the French Institute for Health and Medical Research in Paris.

The study cohort consisted of 10,308 London-based civil servants aged 35-55 years. Every 4-5 years after enrollment, from 1991 through 2016, they completed a questionnaire and had a clinical examination. The U.K. National Health Service electronic health record system tracked outcomes for all but 10 participants through March 2019.

The study identified the individual metabolic syndrome components that posed the highest risk for dementia in these three age groups:

• Age < 60 years: elevated waist circumference (HR 1.39 [95% CI 1.07, 1.81]), low HDL-C, (HR 1.30 [95% CI 1.02, 1.66]), and elevated blood pressure (HR 1.34 [95% CI 1.09, 1.63]).
• Age 60-70 years: low HDL-C (HR 1.26 [95% CI 1.02, 1.57]) and elevated fasting glucose (HR 1.40 [95% CI 1.12, 1.74]).
• Age >70 years: elevated fasting glucose (HR 1.38 [95% CI 1.07, 1.79]).

The study found that the dementia risk was significantly high in study participants under age 60 who had at least one (HR 1.99 [95% CI 1.08, 3.66]) or two (HR 1.69 [95% CI 1.12, 2.56]) metabolic syndrome components even when they didn’t have CVD.

“The present study adds to the understanding of the association between metabolic syndrome and dementia due to three novel features,” Dr. Machado-Fragua said. “First, we tested alternative thresholds to define ‘high metabolic risk,’ and findings show increased risk of dementia to start with the presence of one metabolic syndrome component. Second, assessment of metabolic syndrome components in midlife and later life allowed the examination of the role of age at prevalence of metabolic risk for incident dementia at older ages. Third, our findings showed high dementia risk in those free of cardiovascular disease during follow-up, suggesting that the association between high metabolic risk and incident dementia is not fully explained by cardiovascular disease.”

Dr. Machado-Fragua added, “For now, a cure for dementia remains elusive, making it important to think of prevention strategies. Our findings support targeting the components of the metabolic syndrome in midlife, even in those who have fewer than three of the metabolic syndrome components.”

Applicability ‘confusing’

In an interview, Yehuda Handelsman, MD, questioned the applicability of the study findings in the clinic. “Metabolic syndrome is a clinical manifestation of insulin resistance,” he said. “The more metabolic syndrome criteria a person has, the more insulin resistant that person will be. There is literature that is [suggesting] that insulin resistance is an important cause of dementia.”

The finding of a higher dementia risk before age 70, compared to afterward, makes the applicability “even more confusing,” he said. The results are even more muddled for U.S. physicians, who have moved away from the term metabolic syndrome in favor of cardiometabolic syndrome, said Dr. Handelsman, medical director and principal investigator at the Metabolic Institute of America and president of the Diabetes CardioRenal & Metabolism Institute, both in Tarzana, Calif.

Confusion also surrounds one of the components of metabolic syndrome: Waist circumference, per the harmonized definition the study used, and body mass index, which the more traditional definition uses.

Nonetheless, metabolic syndrome can be used as “kind of a risk calculator” for CVD, diabetes, and dementia, he said. One strength of the study, Dr. Handelsman said, is its size and scope, following 28 years of data. But a weakness was its observational design. “It doesn’t evaluate any true intervention to modify risk,” he said.

Dr. Machado-Fragua and coauthors have no disclosures.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

A version of this article first appeared on Medscape.com.

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

A version of this article first appeared on Medscape.com.

*This article was updated on July 27, 2022.

Ongoing follow-up and lifestyle interventions are needed in lean patients with nonalcoholic fatty liver disease (NAFLD), suggests a panel of experts in a recent review.

They also urge screening for NAFLD in individuals who are older than 40 years with type 2 diabetes, even if they are not overweight.

NAFLD is a leading cause of chronic liver disease that affects more than 25% of the United States and worldwide populations, note lead author Michelle T. Long, MD, Boston Medical Center, Boston University, and colleagues.

Evidence-based approaches

The 15 best practice advice statements covered a wide range of clinical areas, first defining lean as a body mass index (BMI) less than 25 in non-Asian persons and less than 23 in Asian persons.

The authors go on to stipulate, for example, that lean individuals in the general population should not be screened for NAFLD but that screening should be considered for individuals older than 40 years with type 2 diabetes.

More broadly, they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.

After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.

They also write that the NAFLD fibrosis score and Fibrosis-4 score, along with imaging techniques, may be used as alternatives to biopsy for staging and during follow-up.

The authors, who provide a diagnosis and management algorithm to aid clinicians, suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.

Vitamin E may be considered, they continue, in patients with biopsy-confirmed nonalcoholic steatohepatitis but without type 2 diabetes or cirrhosis. Additionally, oral pioglitazone may be considered in lean persons with biopsy-confirmed nonalcoholic steatohepatitis without cirrhosis.

In contrast, they write that the role of glucagonlike peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors requires further investigation.

The advice also says that lean patients with NAFLD should be routinely evaluated for comorbid conditions, such as type 2 diabetes, dyslipidemia, and hypertension, and risk-stratified for hepatic fibrosis to identify those with advanced fibrosis or cirrhosis.

For lean patients with NAFLD and clinical markers compatible with liver cirrhosis, twice-yearly surveillance for hepatocellular carcinoma is also advised.

Fatty liver disease in lean people with metabolic conditions

Approached for comment, Liyun Yuan, MD, PhD, assistant professor of clinical medicine, University of Southern California, Los Angeles, said it is very important to have uniform guidelines for general practitioners and other specialties on NAFLD in lean individuals.

Dr. Yuan, who was not involved in the review, told this news organization that it is crucial to raise awareness of NAFLD, just like awareness of breast cancer screening among women of a certain age was increased, so that individuals are screened for metabolic conditions regardless of whether they have obesity or overweight.

Zobair Younossi, MD, MPH, professor of medicine, Virginia Commonwealth University, Inova Campus, Falls Church, Va., added that there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.

He said in an interview that although it is accurate to define individuals as being lean in terms of their BMI, the best way is to look not only at BMI but also at waist circumference.

Dr. Younossi said that he and his colleagues have shown that when BMI is combined with waist circumference, the prediction of mortality risk in NAFLD is affected, such that lean individuals with an obese waist circumference have a higher risk for all-cause mortality.

Dr. Long is supported in part by the National Institute of Diabetes and Digestive and Kidney Diseases, Doris Duke Charitable Foundation, Gilead Sciences Research Scholars Award, Boston University School of Medicine Department of Medicine Career Investment Award, and Boston University Clinical Translational Science Institute. Dr. Long declares relationships with Novo Nordisk, Echosens Corporation, and Gilead Sciences. Dr. Yuan declares relationships with Genfit, Intercept, and Gilead Sciences. Dr. Younossi declares no relevant relationships.

A version of this article first appeared on Medscape.com.

*This article was updated on July 27, 2022.

The global prevalence of fatty liver disease not caused by alcohol is considerably higher than previously estimated and is continuing to increase at an alarming rate, report researchers from Canada.

Their analysis suggests nearly one-third of the global general adult population has nonalcoholic fatty liver disease (NAFLD), with men much more likely to have the disease than women.

“Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are needed to address the growing burden NAFLD,” wrote Abdel-Aziz Shaheen, MBBCh, MSc, and colleagues with the University of Calgary (Alta.).

The study was published online in Lancet Gastroenterology and Hepatology.

NAFLD is the most common liver disease worldwide and a leading cause of liver-related illness and death. Yet, high-quality reports on the epidemiology of NAFLD at a global level are scarce and temporal trends of the NAFLD burden, including by gender, have not been described, until now.

Using MEDLINE, EMBASE, Scopus, and Web of Science, the Calgary team identified reports on NAFLD incidence and prevalence in study populations representative of the general adult population published between the date of database inception to May 25, 2021.

In total, 72 publications, with a sample population of more than 1 million adults from 17 countries, were included in the prevalence analysis, and 16 publications, with a sample population of nearly 382,000 individuals from five countries, were included in the incidence analysis.

By their estimates, the overall global prevalence of NAFLD is 32.4%, with prevalence increasing steadily and significantly over time, from 25.5% in or before 2005 to 37.8% in 2016 or later. The overall prevalence is significantly higher in men than in women (39.7% vs. 25.6%).

These figures contrast with recent meta-analyses and systematic reviews that put the global prevalence of NAFLD at between 25.2% and 29.8%. However, these studies had “considerable” limitations with “potentially biased inferences,” Dr. Shaheen and colleagues noted.

By region, their data put the prevalence of NAFLD at 31.6% in Asia, 32.6% in Europe, 47.8% in North America, and 56.8% in Africa.

Dr. Shaheen and colleagues estimate the overall incidence of NAFLD to be 46.9 cases per 1,000 person-years, with a higher incidence in men than women (70.8 vs. 29.6 cases per 1000 person-years), in line with the gender differences in prevalence.

They caution that there was “considerable” heterogeneity between studies in both NAFLD prevalence and incidence (I₂ = 99.9%) and few “high-quality” studies.

Despite these limitations, Dr. Shaheen and colleagues said the rise in NAFLD prevalence “should drive enhanced awareness of NAFLD at the level of primary care physicians, public health specialists, and health policy makers to encourage the development of more effective preventive policies.”

Funding for the study was provided by the Canadian Institutes of Health. Dr. Shaheen has received research grants from Gilead and Intercept, and honoraria from SCOPE Canada.

A version of this article first appeared on Medscape.com.

The global prevalence of fatty liver disease not caused by alcohol is considerably higher than previously estimated and is continuing to increase at an alarming rate, report researchers from Canada.

Their analysis suggests nearly one-third of the global general adult population has nonalcoholic fatty liver disease (NAFLD), with men much more likely to have the disease than women.

“Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are needed to address the growing burden NAFLD,” wrote Abdel-Aziz Shaheen, MBBCh, MSc, and colleagues with the University of Calgary (Alta.).

The study was published online in Lancet Gastroenterology and Hepatology.

NAFLD is the most common liver disease worldwide and a leading cause of liver-related illness and death. Yet, high-quality reports on the epidemiology of NAFLD at a global level are scarce and temporal trends of the NAFLD burden, including by gender, have not been described, until now.

Using MEDLINE, EMBASE, Scopus, and Web of Science, the Calgary team identified reports on NAFLD incidence and prevalence in study populations representative of the general adult population published between the date of database inception to May 25, 2021.

In total, 72 publications, with a sample population of more than 1 million adults from 17 countries, were included in the prevalence analysis, and 16 publications, with a sample population of nearly 382,000 individuals from five countries, were included in the incidence analysis.

By their estimates, the overall global prevalence of NAFLD is 32.4%, with prevalence increasing steadily and significantly over time, from 25.5% in or before 2005 to 37.8% in 2016 or later. The overall prevalence is significantly higher in men than in women (39.7% vs. 25.6%).

These figures contrast with recent meta-analyses and systematic reviews that put the global prevalence of NAFLD at between 25.2% and 29.8%. However, these studies had “considerable” limitations with “potentially biased inferences,” Dr. Shaheen and colleagues noted.

By region, their data put the prevalence of NAFLD at 31.6% in Asia, 32.6% in Europe, 47.8% in North America, and 56.8% in Africa.

Dr. Shaheen and colleagues estimate the overall incidence of NAFLD to be 46.9 cases per 1,000 person-years, with a higher incidence in men than women (70.8 vs. 29.6 cases per 1000 person-years), in line with the gender differences in prevalence.

They caution that there was “considerable” heterogeneity between studies in both NAFLD prevalence and incidence (I₂ = 99.9%) and few “high-quality” studies.

Despite these limitations, Dr. Shaheen and colleagues said the rise in NAFLD prevalence “should drive enhanced awareness of NAFLD at the level of primary care physicians, public health specialists, and health policy makers to encourage the development of more effective preventive policies.”

Funding for the study was provided by the Canadian Institutes of Health. Dr. Shaheen has received research grants from Gilead and Intercept, and honoraria from SCOPE Canada.

A version of this article first appeared on Medscape.com.

The global prevalence of fatty liver disease not caused by alcohol is considerably higher than previously estimated and is continuing to increase at an alarming rate, report researchers from Canada.

Their analysis suggests nearly one-third of the global general adult population has nonalcoholic fatty liver disease (NAFLD), with men much more likely to have the disease than women.

“Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are needed to address the growing burden NAFLD,” wrote Abdel-Aziz Shaheen, MBBCh, MSc, and colleagues with the University of Calgary (Alta.).

The study was published online in Lancet Gastroenterology and Hepatology.

NAFLD is the most common liver disease worldwide and a leading cause of liver-related illness and death. Yet, high-quality reports on the epidemiology of NAFLD at a global level are scarce and temporal trends of the NAFLD burden, including by gender, have not been described, until now.

Using MEDLINE, EMBASE, Scopus, and Web of Science, the Calgary team identified reports on NAFLD incidence and prevalence in study populations representative of the general adult population published between the date of database inception to May 25, 2021.

In total, 72 publications, with a sample population of more than 1 million adults from 17 countries, were included in the prevalence analysis, and 16 publications, with a sample population of nearly 382,000 individuals from five countries, were included in the incidence analysis.

By their estimates, the overall global prevalence of NAFLD is 32.4%, with prevalence increasing steadily and significantly over time, from 25.5% in or before 2005 to 37.8% in 2016 or later. The overall prevalence is significantly higher in men than in women (39.7% vs. 25.6%).

These figures contrast with recent meta-analyses and systematic reviews that put the global prevalence of NAFLD at between 25.2% and 29.8%. However, these studies had “considerable” limitations with “potentially biased inferences,” Dr. Shaheen and colleagues noted.

By region, their data put the prevalence of NAFLD at 31.6% in Asia, 32.6% in Europe, 47.8% in North America, and 56.8% in Africa.

Dr. Shaheen and colleagues estimate the overall incidence of NAFLD to be 46.9 cases per 1,000 person-years, with a higher incidence in men than women (70.8 vs. 29.6 cases per 1000 person-years), in line with the gender differences in prevalence.

They caution that there was “considerable” heterogeneity between studies in both NAFLD prevalence and incidence (I₂ = 99.9%) and few “high-quality” studies.

Despite these limitations, Dr. Shaheen and colleagues said the rise in NAFLD prevalence “should drive enhanced awareness of NAFLD at the level of primary care physicians, public health specialists, and health policy makers to encourage the development of more effective preventive policies.”

Funding for the study was provided by the Canadian Institutes of Health. Dr. Shaheen has received research grants from Gilead and Intercept, and honoraria from SCOPE Canada.

A version of this article first appeared on Medscape.com.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

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COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.