CAD & Atherosclerosis

TOPLINE:

Higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk for cardiovascular diseases (CVDs) such as ischemic heart disease, stroke, and congestive heart failure in patients with ankylosing spondylitis (AS) compared with lower doses.

METHODOLOGY:

• NSAIDs can suppress inflammation and relieve pain in patients with AS, but long-term treatment with NSAIDs poses concerns regarding gastrointestinal and renal toxicities and increased CVD risk.
• This nationwide cohort study used data from the Korean National Health Insurance database to investigate the risk for CVD associated with an increasing NSAID dosage in a real-world AS cohort.
• Investigators recruited 19,775 patients (mean age, 36.1 years; 75% men) with newly diagnosed AS and without any prior CVD between January 2010 and December 2018, among whom 99.7% received NSAID treatment and 30.2% received tumor necrosis factor inhibitor treatment.
• A time-varying approach was used to assess the NSAID exposure, wherein periods of NSAID use were defined as “NSAID-exposed” and periods longer than 1 month without NSAID use were defined as “NSAID-unexposed.”
• The primary outcome was the composite outcome of ischemic heart disease, stroke, or congestive heart failure.

TAKEAWAY:

• During the follow-up period of 98,290 person-years, 1663 cases of CVD were identified, which included 1157 cases of ischemic heart disease, 301 cases of stroke, and 613 cases of congestive heart failure.
• After adjusting for confounders, each defined daily dose increase in NSAIDs raised the risk for incident CVD by 10% (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.08-1.13).
• Similarly, increasing the dose of NSAIDs was associated with an increased risk for ischemic heart disease (aHR, 1.08; 95% CI, 1.05-1.11), stroke (aHR, 1.09; 95% CI, 1.04-1.15), and congestive heart failure (aHR, 1.12; 95% CI, 1.08-1.16).
• The association between increasing NSAID dose and increased CVD risk was consistent across various subgroups, with NSAIDs posing a greater threat to cardiovascular health in women than in men.

IN PRACTICE:

The authors wrote, “Taken together, these results suggest that increasing the dose of NSAIDs is associated with a higher cardiovascular risk in AS, but that the increased risk might be lower than that in the general population.”

SOURCE:

First author Ji-Won Kim, MD, PhD, of the Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, the Republic of Korea, and colleagues had their work published online on April 9 in Annals of the Rheumatic Diseases.

LIMITATIONS:

The study was of retrospective nature. The levels of acute phase reactants and AS disease activity could not be determined owing to a lack of data in the National Health Insurance database. The accuracy of the diagnosis of cardiovascular outcomes on the basis of the International Classification of Disease codes was also questionable.

DISCLOSURES:

The study was supported by the National Research Foundation of Korea. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk for cardiovascular diseases (CVDs) such as ischemic heart disease, stroke, and congestive heart failure in patients with ankylosing spondylitis (AS) compared with lower doses.

METHODOLOGY:

• NSAIDs can suppress inflammation and relieve pain in patients with AS, but long-term treatment with NSAIDs poses concerns regarding gastrointestinal and renal toxicities and increased CVD risk.
• This nationwide cohort study used data from the Korean National Health Insurance database to investigate the risk for CVD associated with an increasing NSAID dosage in a real-world AS cohort.
• Investigators recruited 19,775 patients (mean age, 36.1 years; 75% men) with newly diagnosed AS and without any prior CVD between January 2010 and December 2018, among whom 99.7% received NSAID treatment and 30.2% received tumor necrosis factor inhibitor treatment.
• A time-varying approach was used to assess the NSAID exposure, wherein periods of NSAID use were defined as “NSAID-exposed” and periods longer than 1 month without NSAID use were defined as “NSAID-unexposed.”
• The primary outcome was the composite outcome of ischemic heart disease, stroke, or congestive heart failure.

TAKEAWAY:

• During the follow-up period of 98,290 person-years, 1663 cases of CVD were identified, which included 1157 cases of ischemic heart disease, 301 cases of stroke, and 613 cases of congestive heart failure.
• After adjusting for confounders, each defined daily dose increase in NSAIDs raised the risk for incident CVD by 10% (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.08-1.13).
• Similarly, increasing the dose of NSAIDs was associated with an increased risk for ischemic heart disease (aHR, 1.08; 95% CI, 1.05-1.11), stroke (aHR, 1.09; 95% CI, 1.04-1.15), and congestive heart failure (aHR, 1.12; 95% CI, 1.08-1.16).
• The association between increasing NSAID dose and increased CVD risk was consistent across various subgroups, with NSAIDs posing a greater threat to cardiovascular health in women than in men.

IN PRACTICE:

The authors wrote, “Taken together, these results suggest that increasing the dose of NSAIDs is associated with a higher cardiovascular risk in AS, but that the increased risk might be lower than that in the general population.”

SOURCE:

First author Ji-Won Kim, MD, PhD, of the Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, the Republic of Korea, and colleagues had their work published online on April 9 in Annals of the Rheumatic Diseases.

LIMITATIONS:

The study was of retrospective nature. The levels of acute phase reactants and AS disease activity could not be determined owing to a lack of data in the National Health Insurance database. The accuracy of the diagnosis of cardiovascular outcomes on the basis of the International Classification of Disease codes was also questionable.

DISCLOSURES:

The study was supported by the National Research Foundation of Korea. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk for cardiovascular diseases (CVDs) such as ischemic heart disease, stroke, and congestive heart failure in patients with ankylosing spondylitis (AS) compared with lower doses.

METHODOLOGY:

• NSAIDs can suppress inflammation and relieve pain in patients with AS, but long-term treatment with NSAIDs poses concerns regarding gastrointestinal and renal toxicities and increased CVD risk.
• This nationwide cohort study used data from the Korean National Health Insurance database to investigate the risk for CVD associated with an increasing NSAID dosage in a real-world AS cohort.
• Investigators recruited 19,775 patients (mean age, 36.1 years; 75% men) with newly diagnosed AS and without any prior CVD between January 2010 and December 2018, among whom 99.7% received NSAID treatment and 30.2% received tumor necrosis factor inhibitor treatment.
• A time-varying approach was used to assess the NSAID exposure, wherein periods of NSAID use were defined as “NSAID-exposed” and periods longer than 1 month without NSAID use were defined as “NSAID-unexposed.”
• The primary outcome was the composite outcome of ischemic heart disease, stroke, or congestive heart failure.

TAKEAWAY:

• During the follow-up period of 98,290 person-years, 1663 cases of CVD were identified, which included 1157 cases of ischemic heart disease, 301 cases of stroke, and 613 cases of congestive heart failure.
• After adjusting for confounders, each defined daily dose increase in NSAIDs raised the risk for incident CVD by 10% (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.08-1.13).
• Similarly, increasing the dose of NSAIDs was associated with an increased risk for ischemic heart disease (aHR, 1.08; 95% CI, 1.05-1.11), stroke (aHR, 1.09; 95% CI, 1.04-1.15), and congestive heart failure (aHR, 1.12; 95% CI, 1.08-1.16).
• The association between increasing NSAID dose and increased CVD risk was consistent across various subgroups, with NSAIDs posing a greater threat to cardiovascular health in women than in men.

IN PRACTICE:

The authors wrote, “Taken together, these results suggest that increasing the dose of NSAIDs is associated with a higher cardiovascular risk in AS, but that the increased risk might be lower than that in the general population.”

SOURCE:

First author Ji-Won Kim, MD, PhD, of the Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, the Republic of Korea, and colleagues had their work published online on April 9 in Annals of the Rheumatic Diseases.

LIMITATIONS:

The study was of retrospective nature. The levels of acute phase reactants and AS disease activity could not be determined owing to a lack of data in the National Health Insurance database. The accuracy of the diagnosis of cardiovascular outcomes on the basis of the International Classification of Disease codes was also questionable.

DISCLOSURES:

The study was supported by the National Research Foundation of Korea. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

A new systematic literature review adds complexity to the controversy over testosterone’s relationship to risk for myocardial infarction, stroke, cardiovascular death, and all-cause mortality.

Last year, the TRAVERSE (Testosterone Replacement Therapy for Assessment of Long-term Vascular Events and Efficacy ResponSE in Hypogonadal Men) trial was the first randomized, placebo-controlled study designed and powered to determine whether testosterone therapy increased risk for major cardiovascular events in men (ages 45-80 years). Its conclusions provided reassurance that modest use of testosterone therapy short term does not increase CVD risk.

But other studies have had different conclusions and TRAVERSE left unanswered questions, so Bu B. Yeap, MBBS, PhD, an endocrinologist at the University of Western Australia in Crawley, and colleagues completed a literature review with 11 prospective cohort studies of community-dwelling men with sex steroid levels measured with mass spectrometry. Nine of the studies provided individual participation data (IPD); two used aggregate data, and all had at least 5 years of follow-up.

The findings were published in Annals of Internal Medicine .

Dr. Yeap’s team concluded that certain groups of men have higher risk for CVD events. In this study, men with very low testosterone, high luteinizing hormone (LH), or very low estradiol concentrations had higher all-cause mortality. Sex hormone–binding globulin (SHBG) concentration was positively associated and dihydrotestosterone (DHT) levels were nonlinearly associated with all-cause mortality and CVD mortality.

The testosterone level below which men had higher risk of death from any cause was 7.4 nmol/L (213 ng/dL), regardless of LH concentration, the researchers concluded, writing, “This adds to information on reference ranges based on distributions of testosterone in selected samples of healthy men.”

The link between higher SHBG concentrations and higher all-cause mortality “may be related to its role as the major binding protein for sex steroids in the circulation,” the authors wrote. “We found a U-shaped association of DHT with all-cause and CVD-related mortality risks, which were higher at lower and very high DHT concentrations. Men with very low DHT concentrations also had increased risk for incident CVD events. Further investigation into potential underlying mechanisms for these associations is warranted.”
 

Rigorous Methodology Adds Value

Bradley D. Anawalt, MD, with the University of Washington School of Medicine in Seattle, pointed out in an accompanying editorial that the study’s findings are particularly valuable because of the team’s rigorous methodology. The team measured testosterone with the gold standard, mass spectrometry, which can also measure DHT and estradiol more accurately than widely available commercial immunoassays, which “are inaccurate for measurement of these sex steroids in men, who typically have low serum concentrations of these two metabolites of testosterone,” Dr. Anawalt said.

Also, the researchers obtained raw data from the nine IPD studies and reanalyzed the combined data, which allows for more sophisticated analysis when combining data from multiple studies, Dr. Anawalt explained.

The main finding from the Yeap et al. study, he wrote, is that high testosterone concentrations at baseline were not linked with increased deaths from CVD or from all causes “but very low serum total testosterone concentrations at baseline were.

“It is tempting to hypothesize that testosterone therapy might have cardiovascular benefits solely in patients with very low concentrations of serum total testosterone,” Dr. Anawalt wrote.

He pointed out as particularly interesting the findings for DHT and estradiol.

“The finding that a low serum estradiol concentration is associated with higher all-cause mortality adds another reason (in addition to the adverse effects on body fat and bone health) to avoid aromatase inhibitors that are commonly taken by persons who use anabolic steroids,” he wrote. “The prospect of a U-shaped curve for the relationship between serum DHT and higher cardiovascular risk warrants further study.”

The work is funded by the Government of Western Australia and Lawley Pharmaceuticals. The authors’ and editorial writer’s conflicts of interest are listed in the full study.

Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise. 

Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.

My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.

But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.

A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
 

Multiple Ways to Slice the Data

Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality. 

Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies. 

You might wonder how there could be thousands of ways to analyze a dataset. I surely did. 

The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.

Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.

For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association. 
 

Is Red Meat Good or Bad?

Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality. 

Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review. 

They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals. 

Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology. 
 

Specification Curve Analyses Results 

Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.

• The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
• The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
• Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
• As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
• Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
• Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.

Paradigm Changing 

As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have. 

Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method. 

Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result. 

Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null. 

What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible. 

The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data. 

I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices? 

Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.

 

Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise. 

Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.

My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.

But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.

A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
 

Multiple Ways to Slice the Data

Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality. 

Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies. 

You might wonder how there could be thousands of ways to analyze a dataset. I surely did. 

The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.

Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.

For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association. 
 

Is Red Meat Good or Bad?

Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality. 

Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review. 

They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals. 

Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology. 
 

Specification Curve Analyses Results 

Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.

• The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
• The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
• Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
• As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
• Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
• Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.

Paradigm Changing 

As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have. 

Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method. 

Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result. 

Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null. 

What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible. 

The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data. 

I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices? 

Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.

 

Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Observational studies on red meat consumption and lifespan are prime examples of attempts to find signal in a sea of noise. 

Randomized controlled trials are the best way to sort cause from mere correlation. But these are not possible in most matters of food consumption. So, we look back and observe groups with different exposures.

My most frequent complaint about these nonrandom comparison studies has been the chance that the two groups differ in important ways, and it’s these differences — not the food in question — that account for the disparate outcomes.

But selection biases are only one issue. There is also the matter of analytic flexibility. Observational studies are born from large databases. Researchers have many choices in how to analyze all these data.

A few years ago, Brian Nosek, PhD, and colleagues elegantly showed that analytic choices can affect results. His Many Analysts, One Data Set study had little uptake in the medical community, perhaps because he studied a social science question.
 

Multiple Ways to Slice the Data

Recently, a group from McMaster University, led by Dena Zeraatkar, PhD, has confirmed the analytic choices problem, using the question of red meat consumption and mortality. 

Their idea was simple: Because there are many plausible and defensible ways to analyze a dataset, we should not choose one method; rather, we should choose thousands, combine the results, and see where the truth lies. 

You might wonder how there could be thousands of ways to analyze a dataset. I surely did. 

The answer stems from the choices that researchers face. For instance, there is the selection of eligible participants, the choice of analytic model (logistic, Poisson, etc.), and covariates for which to adjust. Think exponents when combining possible choices.

Dr. Zeraatkar and colleagues are research methodologists, so, sadly, they are comfortable with the clunky name of this approach: specification curve analysis. Don’t be deterred. It means that they analyze the data in thousands of ways using computers. Each way is a specification. In the end, the specifications give rise to a curve of hazard ratios for red meat and mortality. Another name for this approach is multiverse analysis.

For their paper in the Journal of Clinical Epidemiology, aptly named “Grilling the Data,” they didn’t just conjure up the many analytic ways to study the red meat–mortality question. Instead, they used a published systematic review of 15 studies on unprocessed red meat and early mortality. The studies included in this review reported 70 unique ways to analyze the association. 
 

Is Red Meat Good or Bad?

Their first finding was that this analysis yielded widely disparate effect estimates, from 0.63 (reduced risk for early death) to 2.31 (a higher risk). The median hazard ratio was 1.14 with an interquartile range (IQR) of 1.02-1.23. One might conclude from this that eating red meat is associated with a slightly higher risk for early mortality. 

Their second step was to calculate how many ways (specifications) there were to analyze the data by totaling all possible combinations of choices in the 70 ways found in the systematic review. 

They calculated a total of 10 quadrillion possible unique analyses. A quadrillion is 1 with 15 zeros. Computing power cannot handle that amount of analyses yet. So, they generated 20 random unique combinations of covariates, which narrowed the number of analyses to about 1400. About 200 of these were excluded due to implausibly wide confidence intervals. 

Voilà. They now had about 1200 different ways to analyze a dataset; they chose an NHANES longitudinal cohort study from 2007-2014. They deemed each of the more than 1200 approaches plausible because they were derived from peer-reviewed papers written by experts in epidemiology. 
 

Specification Curve Analyses Results 

Each analysis (or specification) yielded a hazard ratio for red meat exposure and death.

• The median HR was 0.94 (IQR, 0.83-1.05) for the effect of red meat on all-cause mortality — ie, not significant.
• The range of hazard ratios was large. They went from 0.51 — a 49% reduced risk for early mortality — to 1.75: a 75% increase in early mortality.
• Among all analyses, 36% yielded hazard ratios above 1.0 and 64% less than 1.0.
• As for statistical significance, defined as P ≤.05, only 4% (or 48 specifications) met this threshold. Zeraatkar reminded me that this is what you’d expect if unprocessed red meat has no effect on longevity.
• Of the 48 analyses deemed statistically significant, 40 indicated that red meat consumption reduced early death and eight indicated that eating red meat led to higher mortality.
• Nearly half the analyses yielded unexciting point estimates, with hazard ratios between 0.90 and 1.10.

Paradigm Changing 

As a user of evidence, I find this a potentially paradigm-changing study. Observational studies far outnumber randomized trials. For many medical questions, observational data are all we have. 

Now think about every observational study published. The authors tell you — post hoc — which method they used to analyze the data. The key point is that it is one method. 

Dr. Zeraatkar and colleagues have shown that there are thousands of plausible ways to analyze the data, and this can lead to very different findings. In the specific question of red meat and mortality, their many analyses yielded a null result. 

Now imagine other cases where the researchers did many analyses of a dataset and chose to publish only the significant ones. Observational studies are rarely preregistered, so a reader cannot know how a result would vary depending on analytic choices. A specification curve analysis of a dataset provides a much broader picture. In the case of red meat, you see some significant results, but the vast majority hover around null. 

What about the difficulty in analyzing a dataset 1000 different ways? Dr. Zeraatkar told me that it is harder than just choosing one method, but it’s not impossible. 

The main barrier to adopting this multiverse approach to data, she noted, was not the extra work but the entrenched belief among researchers that there is a best way to analyze data. 

I hope you read this paper and think about it every time you read an observational study that finds a positive or negative association between two things. Ask: What if the researchers were as careful as Dr. Zeraatkar and colleagues and did multiple different analyses? Would the finding hold up to a series of plausible analytic choices? 

Nutritional epidemiology would benefit greatly from this approach. But so would any observational study of an exposure and outcome. I suspect that the number of “positive” associations would diminish. And that would not be a bad thing.

 

Dr. Mandrola, a clinical electrophysiologist at Baptist Medical Associates, Louisville, Kentucky, disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.

Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.

In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.

“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.

The Inflammatory Pathway

Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.

“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation. 

Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.

“This is where colchicine can potentially play a role,” she said. 

Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.

The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted. 

Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.

Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.

What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.

“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.

“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
 

Slow to Embrace Colchicine

Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.

NYU Langone

“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.

Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.

Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.

Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.

A version of this article appeared on Medscape.com .

NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.

Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.

In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.

“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.

The Inflammatory Pathway

Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.

“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation. 

Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.

“This is where colchicine can potentially play a role,” she said. 

Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.

The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted. 

Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.

Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.

What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.

“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.

“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
 

Slow to Embrace Colchicine

Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.

NYU Langone

“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.

Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.

Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.

Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.

A version of this article appeared on Medscape.com .

NEW YORK — New insights into colchicine’s disruption of the pathway that contributes to arterial inflammation and new clinical studies of the drug could pave the way toward greater use of the anti-inflammatory drug in patients with or at risk for atherosclerotic cardiovascular disease (ASCVD), researchers said at the 4th Annual Cardiometabolic Risk in Inflammatory Conditions conference.

Colchicine was approved by the US Food and Drug Administration (FDA) in June 2023 in a once-daily 0.5-mg formulation under the brand name Lodoco to reduce the risk for major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or with multiple risk factors for CVD. The Lodoco formulation is slightly smaller than the 0.6-mg formulation that’s taken twice daily for the prophylaxis and treatment of acute gout flares.

In a presentation at the conference, Binita Shah, MD, one of the principal investigators in trials of Lodoco, explained how the inflammatory pathway contributes to atherosclerosis and provided an update on how colchicine disrupts the pathway. Dr. Shah is an associate professor of medicine at New York University in New York City and director of research at NYU Langone Health Interventional Cardiology.

“Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack,” Shah told this news organization after her presentation.

The Inflammatory Pathway

Dr. Shah explained that normal coronary endothelium resists adhesion by circulating leukocytes, but inflamed or injured coronary endothelium attracts those neutrophils via two types of selectins: L-selectins on neutrophils and E-selectins on endothelial cells. Those neutrophils then release inflammatory cytokines including interleukin-1 beta (IL-1ß), which then triggers production of IL-6 and, subsequently, high-sensitivity C-reactive protein (hsCRP), which contributes to plaque formation, she said.

“Colchicine affects these pathways with a balance for safety and effect on clinical outcomes, particularly to reduce recurrent myocardial infarction [MI],” Dr. Shah said during her presentation. 

Results from the CIRT trial demonstrated that methotrexate is ineffective in blocking the adenosine-mediated anti-inflammatory pathway, Dr. Shah said, so focusing on the IL-1ß–IL-6–hsCRP pathway, which is known to work based on the results of the CANTOS trial, could pay dividends.

“This is where colchicine can potentially play a role,” she said. 

Dr. Shah cited a secondary analysis of the CANTOS trial in which the magnitude of hsCRP reduction correlated with a reduction in MI, stroke, or cardiovascular death. The secondary analysis showed that patients who received canakinumab and achieved hsCRP ≥ 2 mg/L had a nonsignificant 5% lower risk and those who reached < 2 mg/L had a statistically significant 25% lower risk than those who received placebo.

The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, she noted. 

Further clarification of the role of colchicine in managing patients with acute coronary syndrome may come from two other randomized trials now underway, Dr. Shah said: POPCORN is evaluating colchicine to reduce MACE after noncardiac surgery, and CLEAR SYNERGY is evaluating the best timing for colchicine therapy after an acute MI.

Dr. Shah presented preliminary data from her group from a neutrophil biomarker substudy of CLEAR SYNERGY that isolated neutrophils from patients who had an acute MI. “We treated them with various doses of colchicine and showed that the interaction between those treated neutrophils [and] the endothelial cells were a lot lower; they were less sticky to endothelial cells as colchicine was administered,” she said in her presentation. She added that colchicine also reduced neutrophil chemotaxis and neutrophil activation and potentially inhibited inflammasomes, decreasing IL-1ß production.

What’s more, colchicine has been shown to not affect platelets alone but rather platelets at the site of inflammation or plaque rupture, Dr. Shah added. “At currently used doses, colchicine does not inhibit platelet activity [by] itself, so we’ve never seen increased bleeding events, but it will dampen neutrophils’ ability to latch onto a platelet that could contribute to a clot,” she later told this news organization.

“There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease,” she said.

“I think that’s very helpful to know that it’s not just one study — it’s not just a fluke, potentially a play of chance — but multiple studies consistently showing the same thing: That there’s a reduced risk of acute MI.”
 

Slow to Embrace Colchicine

Despite this evidence, cardiologists and rheumatologists have been slow to embrace colchicine for patients at risk for cardiovascular events, said Michael S. Garshick, MD, who attended the conference and is head of the Cardio-Rheumatology Program at NYU Langone. “What [Shah] really highlighted was that for a number of years now, we’ve had several clinical trials showing the benefit of low-dose colchicine to prevent atherosclerotic cardiovascular events, and yet despite these and that there’s now an indication to use low-dose colchicine to reduce cardiovascular disease, we’re still struggling for this medication to be taken up by the general cardiology community to treat high-risk patients.

NYU Langone

“There’s still some work to do to prove that we need to break those barriers,” Dr. Garshick added. Some of the confusion surrounding the use of colchicine for ASCVD may be attributed to the 0.5-mg dose approved for CVD as opposed to the long-approved 0.6-mg dose for gout, he said. “People are generally confused: Is it OK to use the 0.6-mg dose?” Dr. Garshick said.

Potential gastrointestinal side effects may be another concerning factor, although, he added, “we didn’t see any major complications.” Another issue could be polypharmacy in many of these patients, he said.

Dr. Garshick concurred with Shah that the existing evidence supporting the use of colchicine to reduce risk for cardiovascular events is strong, but more will come out. “I think there’s going to be evolving data supporting it,” he said.

Dr. Shah disclosed financial relationships with Philips Volcano and Novo Nordisk. She is a principal investigator of the CLEAR SYNERGY biomarker substudy and the POPCORN trial. Dr. Garshick disclosed relationships with Kiniksa Pharmaceuticals, Agepha Pharma, Bristol Myers Squibb, and Horizon Therapeutics.

A version of this article appeared on Medscape.com .

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

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

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

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

Older men with chronic kidney disease (CKD) show higher resting muscle sympathetic nerve activity, but not vascular stiffness, compared with older women, offering clues to the underlying reasons why men with CKD have a higher cardiovascular risk than do women with the disease.

“Although it is well established that sympathetic nerve system activity is chronically elevated in patients with impaired kidney function, we show for the first time that males with CKD have higher resting muscle sympathetic nerve activity compared with females with CKD,” report the authors on research published in the American Journal of Physiology-Renal Physiology.

“For clinicians, the key takeaway is the importance of recognizing sex-specific differences in sympathetic activity and vascular function when assessing cardiovascular risk in CKD patients,” first author Matias G. Zanuzzi, MD, of the Division of Renal Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, told this news organization.

In the general population, cardiovascular risk is lower in younger women vs men, but their risks converge in older age as women develop similar levels of sympathetic overactivity, vascular stiffness, and cardiovascular risk.

However, an exception to that pattern is seen in the CKD population, where men continue to have a higher cardiovascular mortality risk vs women even in older age.

Studies evaluating the reasons for that have been conflicting, with some reporting a tendency of higher muscle sympathetic nerve activity in older women compared with men and others suggest the opposite finding — lower activity vs men.

To further investigate, Dr. Zanuzzi and colleagues enrolled 129 participants, including 96 men and 33 women with stage III or IV CKD.

The mean age of the study participants was 64 years for men and65 years for women. Most had obesity, and importantly, more than 80% of participants in each group was Black. There were no significant differences between the groups in terms of body mass index or comorbidities, including smoking, diabetes, or hypertension.

At two separate study visits, vascular stiffness was assessed with carotid-femoral pulse wave velocity measurement, and resting muscle sympathetic nerve activity was measured using microneurography. 

The results showed that men with CKD had significantly higher resting muscle sympathetic nerve activity compared with women with CKD (68 vs 55 bursts per 100 heartbeats; P = .005), whereas no differences in vascular stiffness were observed between the genders (P = .248).

“The findings suggest that the higher cardiovascular disease risk observed in older males with CKD may be influenced by elevated sympathetic activity,” Dr. Zanuzzi explained.

“However, the lack of significant differences in vascular stiffness between genders implies that additional factors beyond vascular remodeling may contribute to the observed sex-specific differences in cardiovascular risk,” he said.

Of note, resting vascular stiffness was not associated with muscular sympathetic nerve activity in either men or women, which was surprising to the authors, Dr. Zanuzzi noted.

“This underscores the multifactorial nature of vascular pathophysiology in CKD and underscores the need for further research to unravel the underlying mechanisms.”

In other findings, although prior studies have shown a positive correlation between age and resting muscle sympathetic nerve activity in White, healthy women and men without obesity,, no similar relationship was observed in men or women with CKD.

“These findings suggest that the protective effect of younger age on sympathetic function may not be present in the setting of decreased kidney function in both males and females,” the authors note.

In addition, whereas previous research has shown a clear association between sympathetic overactivity and a wide variety of measures of obesity, in the current study, that association was only observed in men with CKD.

Important limitations of the study include the cross-sectional design and that the population was predominantly Black, Dr. Zanuzzi noted.

“Generalizability to other demographic groups may be limited, and future longitudinal studies are needed to validate these findings and explore potential causal relationships,” he said.

The findings underscore “the need for novel therapeutic approaches targeting sympathetic overactivity and vascular stiffness in CKD patients, especially considering the observed sex-specific differences,” Dr. Zanuzzi added. 

“Potential interventions may include pharmacological agents that modulate sympathetic tone or vascular remodeling pathways,” he said.

“Lifestyle modifications focusing on stress reduction and cardiovascular health promotion could also play a crucial role in mitigating cardiovascular risk.”

Dr. Zanuzzi concluded that “tailoring treatment strategies to address these differences may lead to more personalized and effective management approaches, ultimately improving clinical outcomes in this high-risk population.”

The authors had no disclosures to report.

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

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Metabolic dysfunction-associated steatotic liver disease (MASLD) co-occurring with HIV infection does not appear to increase the risk for cirrhosis or hepatocellular carcinoma (HCC) compared with MASLD alone. However, the incidence of major adverse cardiovascular events (MACE) is significantly increased among patients with MASLD and HIV, a large study suggested.

METHODOLOGY:

• MASLD is highly prevalent in people living with HIV, but the impact of HIV on liver and cardiovascular disease (CVD) outcomes in people with MASLD remains unclear.
• To investigate, researchers created a propensity score-matched cohort of veterans with noncirrhotic MASLD, with and without HIV (920 patients in each group).
• They evaluated the incidence of cirrhosis, HCC, and MACE, as well as overall survival, among the two groups. They also assessed these outcomes in MASLD patients with HIV on the basis of whether they were on antiretroviral therapy (ART).

TAKEAWAY:

• During a median follow-up of 10.4 years in the MASLD with HIV group and 11.8 years in the MASLD-only group, the overall incidence of cirrhosis and HCC was similar in MASLD with vs without HIV (cirrhosis: 0.97 vs 1.06 per 100 person-years, P = .54; HCC: 0.26 vs 0.17 per 100,000 person-years, P = .23), regardless of ART use.

• In contrast, the incidence of MACE was significantly higher in MASLD with vs without HIV (5.18 vs 4.48 per 100 person-years, P = .03). The incidence also was higher in patients with MASLD and HIV who were not on ART compared with those on ART (5.83 vs 4.7 per 100 person-years, P = .07).

• Compared with MASLD without HIV, the overall 5-year survival was significantly lower in MASLD with HIV (91.3% vs 85.7%). In MASLD with HIV, receipt of ART was associated with a significantly higher 5-year survival than no ART (87.4% vs 81.6%).

IN PRACTICE:

“Ensuring timely and appropriate initiation of HIV treatment is critical in patients with MASLD who have concurrent HIV infection, as well as optimizing metabolic comorbidities that may also contribute to increased risks of CVD and increased mortality,” the authors wrote.

SOURCE:

The study, led by Robert J. Wong, MD, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, was published online in the American Journal of Gastroenterology.

LIMITATIONS:

The study cohort consisted predominantly of older men, which may limit generalizability to women and younger populations. Metabolic comorbidities are more common in veterans compared with the general population, potentially affecting the generalizability of the CVD risk findings.

DISCLOSURES:

The study was supported by an investigator-initiated research grant from Theratechnologies. Wong has received funding for his institution from Gilead Sciences, Exact Sciences, and Durect Corporation and has served as a consultant for Gilead Sciences.
 

A version of this article appeared on Medscape.com.

Among adults with type 2 diabetes (T2D) older than 65 years, a body mass index (BMI) in the moderate overweight category (26-28) appears to offer better protection from cardiovascular death than does a BMI in the “normal” range, new data suggested.

On the other hand, the study findings also suggest that the “normal” range of 23-25 is optimal for middle-aged adults with T2D.

The findings reflect a previously demonstrated phenomenon called the “obesity paradox,” in which older people with overweight may have better outcomes than leaner people due to factors such as bone loss, frailty, and nutritional deficits, study lead author Shaoyong Xu, of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China, told this news organization.

“In this era of population growth and aging, the question arises as to whether obesity or overweight can be beneficial in improving survival rates for older individuals with diabetes. This topic holds significant relevance due to the potential implications it has on weight management strategies for older adults. If overweight does not pose an increased risk of cardiovascular mortality, it may suggest that older individuals are not necessarily required to strive for weight loss to achieve so-called normal values.”

Moreover, Dr. Xu added, “inappropriate weight loss and being underweight could potentially elevate the risk of cardiovascular events, myocardial infarction, cerebral infarction, and all-cause mortality.”

Thus, he said, “while there are general guidelines recommending a BMI below 25, our findings suggest that personalized BMI targets may be more beneficial, particularly for different age groups and individuals with specific health conditions.”

Asked to comment, Ian J. Neeland, MD, director of cardiovascular prevention, University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University, Cleveland, Ohio, pointed out that older people who are underweight or in lower weight categories may be more likely to smoke or have undiagnosed cancer, or that “their BMI is not so much reflective of fat mass as of low muscle mass, or sarcopenia, and that is definitely a risk factor for adverse outcomes and risks. ... And those who have slightly higher BMIs may be maintaining muscle mass, even though they’re older, and therefore they have less risk.”

However, Dr. Neeland disagreed with the authors’ conclusions regarding “optimal” BMI. “Just because you have different risk categories based on BMI doesn’t mean that’s ‘optimal’ BMI. The way I would interpret this paper is that there’s an association of mildly overweight with better outcomes in adults who are over 65 with type 2 diabetes. We need to try to understand the mechanisms underlying that observation.”

Dr. Neeland advised that for an older person with T2D who has low muscle mass and frailty, “I wouldn’t recommend necessarily targeted weight loss in that person. But I would potentially recommend weight loss in addition to resistance training, muscle building, and endurance training, and therefore reducing fat mass. The goal would be not so much weight loss but reduction of body fat and maintaining and improving muscle health.”
 

U-Shaped Relationship Found Between Age, BMI, and Cardiovascular Disease (CVD) Risk

The data come from the UK Biobank, a population-based prospective cohort study of adults in the United Kingdom. A total of 22,874 participants with baseline T2D were included in the current study. Baseline surveys were conducted between 2006 and 2010, and follow-up was a median of 12.52 years. During that time, 891 people died of CVD.

Hazard ratios were adjusted for baseline variables including age, sex, smoking history, alcohol consumption, level of physical exercise, and history of CVDs.

Compared with people with BMI a < 25 in the group who were aged 65 years or younger, those with a BMI of 25.0-29.9 had a 13% higher risk for cardiovascular death. However, among those older than 65 years, a BMI between 25.0 and 29.9 was associated with an 18% lower risk.

A U-shaped relationship was found between BMI and the risk for cardiovascular death, with an optimal BMI cutoff of 24.0 in the under-65 group and a 27.0 cutoff in the older group. Ranges of 23.0-25.0 in the under-65 group and 26.0-28 in the older group were associated with the lowest cardiovascular risk.

In contrast, there was a linear relationship between both waist circumference and waist-to-height ratio and the risk for cardiovascular death, making those more direct measures of adiposity, Dr. Xu told this news organization.

“For clinicians, our data underscores the importance of considering age when assessing BMI targets for cardiovascular health. Personalized treatment plans that account for age-specific BMI cutoffs and other risk factors may enhance patient outcomes and reduce CVD mortality,” Dr. Xu said.

However, he added, “while these findings suggest an optimal BMI range, it is crucial to acknowledge that these cutoff points may vary based on gender, race, and other factors. Our future studies will validate these findings in different populations and attempt to explain the mechanism by which the optimal nodal values exist in people with diabetes at different ages.”

Dr. Neeland cautioned, “I think more work needs to be done in terms of not just identifying the risk differences but understanding why and how to better risk stratify individuals and do personalized medicine. I think that’s important, but you have to have good data to support the strategies you’re going to use. These data are observational, and they’re a good start, but they wouldn’t directly impact practice at this point.”

The data will be presented at the European Congress on Obesity taking place May 12-15 in Venice, Italy.

The authors declared no competing interests. Study funding came from several sources, including the Young Talents Project of Hubei Provincial Health Commission, China, Hubei Provincial Natural Science Foundation of China, the Science and Technology Research Key Project of the Education Department of Hubei Province China, and the Sanuo Diabetes Charity Foundation, China, and the Xiangyang Science and Technology Plan Project, China. Dr. Neeland is a speaker and/or consultant for Boehringer Ingelheim, Novo Nordisk, Bayer, and Eli Lilly and Company.
 

A version of this article appeared on Medscape.com.

Among adults with type 2 diabetes (T2D) older than 65 years, a body mass index (BMI) in the moderate overweight category (26-28) appears to offer better protection from cardiovascular death than does a BMI in the “normal” range, new data suggested.

On the other hand, the study findings also suggest that the “normal” range of 23-25 is optimal for middle-aged adults with T2D.

The findings reflect a previously demonstrated phenomenon called the “obesity paradox,” in which older people with overweight may have better outcomes than leaner people due to factors such as bone loss, frailty, and nutritional deficits, study lead author Shaoyong Xu, of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China, told this news organization.

“In this era of population growth and aging, the question arises as to whether obesity or overweight can be beneficial in improving survival rates for older individuals with diabetes. This topic holds significant relevance due to the potential implications it has on weight management strategies for older adults. If overweight does not pose an increased risk of cardiovascular mortality, it may suggest that older individuals are not necessarily required to strive for weight loss to achieve so-called normal values.”

Moreover, Dr. Xu added, “inappropriate weight loss and being underweight could potentially elevate the risk of cardiovascular events, myocardial infarction, cerebral infarction, and all-cause mortality.”

Thus, he said, “while there are general guidelines recommending a BMI below 25, our findings suggest that personalized BMI targets may be more beneficial, particularly for different age groups and individuals with specific health conditions.”

Asked to comment, Ian J. Neeland, MD, director of cardiovascular prevention, University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University, Cleveland, Ohio, pointed out that older people who are underweight or in lower weight categories may be more likely to smoke or have undiagnosed cancer, or that “their BMI is not so much reflective of fat mass as of low muscle mass, or sarcopenia, and that is definitely a risk factor for adverse outcomes and risks. ... And those who have slightly higher BMIs may be maintaining muscle mass, even though they’re older, and therefore they have less risk.”

However, Dr. Neeland disagreed with the authors’ conclusions regarding “optimal” BMI. “Just because you have different risk categories based on BMI doesn’t mean that’s ‘optimal’ BMI. The way I would interpret this paper is that there’s an association of mildly overweight with better outcomes in adults who are over 65 with type 2 diabetes. We need to try to understand the mechanisms underlying that observation.”

Dr. Neeland advised that for an older person with T2D who has low muscle mass and frailty, “I wouldn’t recommend necessarily targeted weight loss in that person. But I would potentially recommend weight loss in addition to resistance training, muscle building, and endurance training, and therefore reducing fat mass. The goal would be not so much weight loss but reduction of body fat and maintaining and improving muscle health.”
 

U-Shaped Relationship Found Between Age, BMI, and Cardiovascular Disease (CVD) Risk

The data come from the UK Biobank, a population-based prospective cohort study of adults in the United Kingdom. A total of 22,874 participants with baseline T2D were included in the current study. Baseline surveys were conducted between 2006 and 2010, and follow-up was a median of 12.52 years. During that time, 891 people died of CVD.

Hazard ratios were adjusted for baseline variables including age, sex, smoking history, alcohol consumption, level of physical exercise, and history of CVDs.

Compared with people with BMI a < 25 in the group who were aged 65 years or younger, those with a BMI of 25.0-29.9 had a 13% higher risk for cardiovascular death. However, among those older than 65 years, a BMI between 25.0 and 29.9 was associated with an 18% lower risk.

A U-shaped relationship was found between BMI and the risk for cardiovascular death, with an optimal BMI cutoff of 24.0 in the under-65 group and a 27.0 cutoff in the older group. Ranges of 23.0-25.0 in the under-65 group and 26.0-28 in the older group were associated with the lowest cardiovascular risk.

In contrast, there was a linear relationship between both waist circumference and waist-to-height ratio and the risk for cardiovascular death, making those more direct measures of adiposity, Dr. Xu told this news organization.

“For clinicians, our data underscores the importance of considering age when assessing BMI targets for cardiovascular health. Personalized treatment plans that account for age-specific BMI cutoffs and other risk factors may enhance patient outcomes and reduce CVD mortality,” Dr. Xu said.

However, he added, “while these findings suggest an optimal BMI range, it is crucial to acknowledge that these cutoff points may vary based on gender, race, and other factors. Our future studies will validate these findings in different populations and attempt to explain the mechanism by which the optimal nodal values exist in people with diabetes at different ages.”

Dr. Neeland cautioned, “I think more work needs to be done in terms of not just identifying the risk differences but understanding why and how to better risk stratify individuals and do personalized medicine. I think that’s important, but you have to have good data to support the strategies you’re going to use. These data are observational, and they’re a good start, but they wouldn’t directly impact practice at this point.”

The data will be presented at the European Congress on Obesity taking place May 12-15 in Venice, Italy.

The authors declared no competing interests. Study funding came from several sources, including the Young Talents Project of Hubei Provincial Health Commission, China, Hubei Provincial Natural Science Foundation of China, the Science and Technology Research Key Project of the Education Department of Hubei Province China, and the Sanuo Diabetes Charity Foundation, China, and the Xiangyang Science and Technology Plan Project, China. Dr. Neeland is a speaker and/or consultant for Boehringer Ingelheim, Novo Nordisk, Bayer, and Eli Lilly and Company.
 

A version of this article appeared on Medscape.com.

Among adults with type 2 diabetes (T2D) older than 65 years, a body mass index (BMI) in the moderate overweight category (26-28) appears to offer better protection from cardiovascular death than does a BMI in the “normal” range, new data suggested.

On the other hand, the study findings also suggest that the “normal” range of 23-25 is optimal for middle-aged adults with T2D.

The findings reflect a previously demonstrated phenomenon called the “obesity paradox,” in which older people with overweight may have better outcomes than leaner people due to factors such as bone loss, frailty, and nutritional deficits, study lead author Shaoyong Xu, of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, China, told this news organization.

“In this era of population growth and aging, the question arises as to whether obesity or overweight can be beneficial in improving survival rates for older individuals with diabetes. This topic holds significant relevance due to the potential implications it has on weight management strategies for older adults. If overweight does not pose an increased risk of cardiovascular mortality, it may suggest that older individuals are not necessarily required to strive for weight loss to achieve so-called normal values.”

Moreover, Dr. Xu added, “inappropriate weight loss and being underweight could potentially elevate the risk of cardiovascular events, myocardial infarction, cerebral infarction, and all-cause mortality.”

Thus, he said, “while there are general guidelines recommending a BMI below 25, our findings suggest that personalized BMI targets may be more beneficial, particularly for different age groups and individuals with specific health conditions.”

Asked to comment, Ian J. Neeland, MD, director of cardiovascular prevention, University Hospitals Harrington Heart & Vascular Institute, Case Western Reserve University, Cleveland, Ohio, pointed out that older people who are underweight or in lower weight categories may be more likely to smoke or have undiagnosed cancer, or that “their BMI is not so much reflective of fat mass as of low muscle mass, or sarcopenia, and that is definitely a risk factor for adverse outcomes and risks. ... And those who have slightly higher BMIs may be maintaining muscle mass, even though they’re older, and therefore they have less risk.”

However, Dr. Neeland disagreed with the authors’ conclusions regarding “optimal” BMI. “Just because you have different risk categories based on BMI doesn’t mean that’s ‘optimal’ BMI. The way I would interpret this paper is that there’s an association of mildly overweight with better outcomes in adults who are over 65 with type 2 diabetes. We need to try to understand the mechanisms underlying that observation.”

Dr. Neeland advised that for an older person with T2D who has low muscle mass and frailty, “I wouldn’t recommend necessarily targeted weight loss in that person. But I would potentially recommend weight loss in addition to resistance training, muscle building, and endurance training, and therefore reducing fat mass. The goal would be not so much weight loss but reduction of body fat and maintaining and improving muscle health.”
 

U-Shaped Relationship Found Between Age, BMI, and Cardiovascular Disease (CVD) Risk

The data come from the UK Biobank, a population-based prospective cohort study of adults in the United Kingdom. A total of 22,874 participants with baseline T2D were included in the current study. Baseline surveys were conducted between 2006 and 2010, and follow-up was a median of 12.52 years. During that time, 891 people died of CVD.

Hazard ratios were adjusted for baseline variables including age, sex, smoking history, alcohol consumption, level of physical exercise, and history of CVDs.

Compared with people with BMI a < 25 in the group who were aged 65 years or younger, those with a BMI of 25.0-29.9 had a 13% higher risk for cardiovascular death. However, among those older than 65 years, a BMI between 25.0 and 29.9 was associated with an 18% lower risk.

A U-shaped relationship was found between BMI and the risk for cardiovascular death, with an optimal BMI cutoff of 24.0 in the under-65 group and a 27.0 cutoff in the older group. Ranges of 23.0-25.0 in the under-65 group and 26.0-28 in the older group were associated with the lowest cardiovascular risk.

In contrast, there was a linear relationship between both waist circumference and waist-to-height ratio and the risk for cardiovascular death, making those more direct measures of adiposity, Dr. Xu told this news organization.

“For clinicians, our data underscores the importance of considering age when assessing BMI targets for cardiovascular health. Personalized treatment plans that account for age-specific BMI cutoffs and other risk factors may enhance patient outcomes and reduce CVD mortality,” Dr. Xu said.

However, he added, “while these findings suggest an optimal BMI range, it is crucial to acknowledge that these cutoff points may vary based on gender, race, and other factors. Our future studies will validate these findings in different populations and attempt to explain the mechanism by which the optimal nodal values exist in people with diabetes at different ages.”

Dr. Neeland cautioned, “I think more work needs to be done in terms of not just identifying the risk differences but understanding why and how to better risk stratify individuals and do personalized medicine. I think that’s important, but you have to have good data to support the strategies you’re going to use. These data are observational, and they’re a good start, but they wouldn’t directly impact practice at this point.”

The data will be presented at the European Congress on Obesity taking place May 12-15 in Venice, Italy.

The authors declared no competing interests. Study funding came from several sources, including the Young Talents Project of Hubei Provincial Health Commission, China, Hubei Provincial Natural Science Foundation of China, the Science and Technology Research Key Project of the Education Department of Hubei Province China, and the Sanuo Diabetes Charity Foundation, China, and the Xiangyang Science and Technology Plan Project, China. Dr. Neeland is a speaker and/or consultant for Boehringer Ingelheim, Novo Nordisk, Bayer, and Eli Lilly and Company.
 

A version of this article appeared on Medscape.com.

Infants born to women with obesity showed improved measures of cardiovascular health when their mothers adopted healthier lifestyles before and during pregnancy, based on data from a systematic review presented at the annual meeting of the Society for Reproductive Investigation.

Previous research has shown that children born to mothers with a high body mass index (BMI) are more likely to die from cardiovascular disease in later life, said presenting author Samuel J. Burden, PhD, in an interview.

“Surprisingly, early signs of these heart issues can start before birth and continue into childhood,” said Dr. Burden, a research associate in the Department of Women & Children’s Health, School of Life Course & Population Sciences, King’s College London, London, United Kingdom.

To examine the effect of interventions such as a healthy diet and exercise in pregnant women with obesity on the heart health of their infants, Dr. Burden and colleagues reviewed data from eight randomized, controlled trials involving diet and exercise for pregnant women with obesity. Of these, two used antenatal exercise, two used diet and physical activity, and one used preconception diet and physical activity. The studies ranged in size from 18 to 404 participants. Two studies included infants younger than 2 months of age, and four studies included children aged 3-7 years.

Overall, lifestyle interventions before conception and before birth were associated with significant changes in cardiac remodeling, specifically reduced interventricular septal wall thickness.

In addition, one of three studies of cardiac diastolic function and four of five studies of systolic function showed significant improvements. The five studies of cardiac systolic function and three studies of diastolic function also showed improvement in systolic and diastolic blood pressure in infants of mothers who took part in the interventions. The studies were limited mainly by large attrition rates, the researchers wrote in their presentation. However, more studies in larger populations that also include older children could confirm the findings and inform public health strategies to promote healthy lifestyles for pregnant women, they noted.

Encourage Healthy Lifestyle Before and During Pregnancy

The evidence supports the findings from animal studies showing that an offspring’s health is influenced by maternal lifestyle before and during pregnancy, Dr. Burden said in an interview. The data suggest that healthcare providers should encourage women with a high BMI who want to become pregnant to eat healthfully and become more active as a way to enhance the future cardiovascular health of their children, he said.

The full results of the current study are soon to be published, but more work is needed, said Dr. Burden. “While we observed a protective effect from these lifestyle programs, there is a need for more extensive studies involving a larger number of women (and their children) who were part of the initial research,” he said. “Additionally, it will be crucial to track these children into adulthood to determine whether these antenatal lifestyle interventions persist in lowering the risk of future cardiovascular disease.”

Beginning healthy lifestyle programs prior to pregnancy might yield the best results for promoting infant cardiovascular health, and more prepregnancy interventions for women with obesity are needed, Dr. Burden added.

The current study adds to the growing body of evidence that the in utero environment can have lifelong effects on offspring, Joseph R. Biggio Jr, MD, system chair of maternal fetal medicine at Ochsner Health, New Orleans, Louisiana, said in an interview.

“Several studies have previously shown that the children of mothers with diabetes, hypertension, or obesity are at increased risk for developing signs of metabolic syndrome and cardiovascular changes during childhood or adolescence,” said Dr. Biggio.

The data from this systematic review support the potential value of interventions aimed at improving maternal weight gain and cardiovascular performance before and during pregnancy that may result in reduced cardiovascular remodeling and myocardial thickening in infants, he said.   

The study was supported by a British Heart Foundation Special Project Grant. The researchers had no financial conflicts to disclose. Dr. Biggio had no financial conflicts to disclose.

Infants born to women with obesity showed improved measures of cardiovascular health when their mothers adopted healthier lifestyles before and during pregnancy, based on data from a systematic review presented at the annual meeting of the Society for Reproductive Investigation.

Previous research has shown that children born to mothers with a high body mass index (BMI) are more likely to die from cardiovascular disease in later life, said presenting author Samuel J. Burden, PhD, in an interview.

“Surprisingly, early signs of these heart issues can start before birth and continue into childhood,” said Dr. Burden, a research associate in the Department of Women & Children’s Health, School of Life Course & Population Sciences, King’s College London, London, United Kingdom.

To examine the effect of interventions such as a healthy diet and exercise in pregnant women with obesity on the heart health of their infants, Dr. Burden and colleagues reviewed data from eight randomized, controlled trials involving diet and exercise for pregnant women with obesity. Of these, two used antenatal exercise, two used diet and physical activity, and one used preconception diet and physical activity. The studies ranged in size from 18 to 404 participants. Two studies included infants younger than 2 months of age, and four studies included children aged 3-7 years.

Overall, lifestyle interventions before conception and before birth were associated with significant changes in cardiac remodeling, specifically reduced interventricular septal wall thickness.

In addition, one of three studies of cardiac diastolic function and four of five studies of systolic function showed significant improvements. The five studies of cardiac systolic function and three studies of diastolic function also showed improvement in systolic and diastolic blood pressure in infants of mothers who took part in the interventions. The studies were limited mainly by large attrition rates, the researchers wrote in their presentation. However, more studies in larger populations that also include older children could confirm the findings and inform public health strategies to promote healthy lifestyles for pregnant women, they noted.

Encourage Healthy Lifestyle Before and During Pregnancy

The evidence supports the findings from animal studies showing that an offspring’s health is influenced by maternal lifestyle before and during pregnancy, Dr. Burden said in an interview. The data suggest that healthcare providers should encourage women with a high BMI who want to become pregnant to eat healthfully and become more active as a way to enhance the future cardiovascular health of their children, he said.

The full results of the current study are soon to be published, but more work is needed, said Dr. Burden. “While we observed a protective effect from these lifestyle programs, there is a need for more extensive studies involving a larger number of women (and their children) who were part of the initial research,” he said. “Additionally, it will be crucial to track these children into adulthood to determine whether these antenatal lifestyle interventions persist in lowering the risk of future cardiovascular disease.”

Beginning healthy lifestyle programs prior to pregnancy might yield the best results for promoting infant cardiovascular health, and more prepregnancy interventions for women with obesity are needed, Dr. Burden added.

The current study adds to the growing body of evidence that the in utero environment can have lifelong effects on offspring, Joseph R. Biggio Jr, MD, system chair of maternal fetal medicine at Ochsner Health, New Orleans, Louisiana, said in an interview.

“Several studies have previously shown that the children of mothers with diabetes, hypertension, or obesity are at increased risk for developing signs of metabolic syndrome and cardiovascular changes during childhood or adolescence,” said Dr. Biggio.

The data from this systematic review support the potential value of interventions aimed at improving maternal weight gain and cardiovascular performance before and during pregnancy that may result in reduced cardiovascular remodeling and myocardial thickening in infants, he said.   

The study was supported by a British Heart Foundation Special Project Grant. The researchers had no financial conflicts to disclose. Dr. Biggio had no financial conflicts to disclose.

Infants born to women with obesity showed improved measures of cardiovascular health when their mothers adopted healthier lifestyles before and during pregnancy, based on data from a systematic review presented at the annual meeting of the Society for Reproductive Investigation.

Previous research has shown that children born to mothers with a high body mass index (BMI) are more likely to die from cardiovascular disease in later life, said presenting author Samuel J. Burden, PhD, in an interview.

“Surprisingly, early signs of these heart issues can start before birth and continue into childhood,” said Dr. Burden, a research associate in the Department of Women & Children’s Health, School of Life Course & Population Sciences, King’s College London, London, United Kingdom.

To examine the effect of interventions such as a healthy diet and exercise in pregnant women with obesity on the heart health of their infants, Dr. Burden and colleagues reviewed data from eight randomized, controlled trials involving diet and exercise for pregnant women with obesity. Of these, two used antenatal exercise, two used diet and physical activity, and one used preconception diet and physical activity. The studies ranged in size from 18 to 404 participants. Two studies included infants younger than 2 months of age, and four studies included children aged 3-7 years.

Overall, lifestyle interventions before conception and before birth were associated with significant changes in cardiac remodeling, specifically reduced interventricular septal wall thickness.

In addition, one of three studies of cardiac diastolic function and four of five studies of systolic function showed significant improvements. The five studies of cardiac systolic function and three studies of diastolic function also showed improvement in systolic and diastolic blood pressure in infants of mothers who took part in the interventions. The studies were limited mainly by large attrition rates, the researchers wrote in their presentation. However, more studies in larger populations that also include older children could confirm the findings and inform public health strategies to promote healthy lifestyles for pregnant women, they noted.

Encourage Healthy Lifestyle Before and During Pregnancy

The evidence supports the findings from animal studies showing that an offspring’s health is influenced by maternal lifestyle before and during pregnancy, Dr. Burden said in an interview. The data suggest that healthcare providers should encourage women with a high BMI who want to become pregnant to eat healthfully and become more active as a way to enhance the future cardiovascular health of their children, he said.

The full results of the current study are soon to be published, but more work is needed, said Dr. Burden. “While we observed a protective effect from these lifestyle programs, there is a need for more extensive studies involving a larger number of women (and their children) who were part of the initial research,” he said. “Additionally, it will be crucial to track these children into adulthood to determine whether these antenatal lifestyle interventions persist in lowering the risk of future cardiovascular disease.”

Beginning healthy lifestyle programs prior to pregnancy might yield the best results for promoting infant cardiovascular health, and more prepregnancy interventions for women with obesity are needed, Dr. Burden added.

The current study adds to the growing body of evidence that the in utero environment can have lifelong effects on offspring, Joseph R. Biggio Jr, MD, system chair of maternal fetal medicine at Ochsner Health, New Orleans, Louisiana, said in an interview.

“Several studies have previously shown that the children of mothers with diabetes, hypertension, or obesity are at increased risk for developing signs of metabolic syndrome and cardiovascular changes during childhood or adolescence,” said Dr. Biggio.

The data from this systematic review support the potential value of interventions aimed at improving maternal weight gain and cardiovascular performance before and during pregnancy that may result in reduced cardiovascular remodeling and myocardial thickening in infants, he said.   

The study was supported by a British Heart Foundation Special Project Grant. The researchers had no financial conflicts to disclose. Dr. Biggio had no financial conflicts to disclose.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are often not prescribed or accessible to people who could benefit from them, a trio of new studies suggested.

First approved for the treatment of type 2 diabetes, the indications for SGLT2 inhibitors and GLP-1 RA medications have now been extended to people with obesity, heart failure, and chronic kidney disease.

The papers were presented at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Scientific Sessions 2024.

The new data show there is “work to be done in terms of access and equity to these treatments,” Robert H. Eckel, MD, who was not involved in the research, said in a conference statement.

“There is no question that the cost of these medications is high, yet when issues go beyond coverage and include sociodemographic and racial differences that influence treatment, these major issues need to be evaluated and addressed,” said Dr. Eckel, professor emeritus of medicine, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Denver, and a past president of the AHA.
 

Low Prescription Rates

In one study, researchers analyzed health records for 18,164 adults with obesity (mean age, 51 years; 64% women; mean body mass index [BMI], 36 kg/m2) who had health insurance covering semaglutide and liraglutide (GLP-1 RAs) and tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide RA). The cohort was 54% White, 35% Black, and 5% Asian.

Only about 3% of eligible adults were prescribed one of these medications, reported Meron Haile, BS, a second-year medical student at Johns Hopkins University School of Medicine in Baltimore, and colleagues.

The likelihood of prescription was lower among Black patients (odds ratio [OR], 0.76) and men (OR, 0.54) and higher in people with higher BMI (OR, 1.06 per 1-unit higher BMI).

Living in a neighborhood with a higher area deprivation index or lower income was not independently associated with the likelihood of prescription.

Individuals with diabetes or hypertension were more likely to be prescribed one of these medications (OR, 3.52 and 1.36, respectively).

“While prescription rates for new obesity therapies are low among the overall population, we saw pronounced lower accessibility among Black adults, who exhibit a higher burden of severe obesity, hypertension, and type 2 diabetes,” Haile said in a conference statement.

“There is a crucial need for understanding prescription practices for obesity medications and to facilitate similar access among people in all races and ethnic groups,” Haile added.

Similar findings emerged in a separate study, in which researchers analyzed the health records of 687,165 adults with type 2 diabetes treated at six large health systems from 2014 to 2022.

The rate of annual pharmacy dispensing of SGLT2 inhibitors and GLP-1 RA medications rose during the study period, but there were clear racial and ethnic differences in prescribing.

In fully adjusted models, SGLT2 inhibitors dispensing was lower for American Indian/Alaska Native (AI/AN; OR, 0.80), Black (OR, 0.89), and Hispanic (OR, 0.87) individuals than for White patients.

Likewise, GLP-1 RA dispensing was also lower for AI/AN (OR, 0.78), Asian (OR, 0.50), Black (OR, 0.86), Hawaiian/Pacific Islander (OR, 0.52), and Hispanic (OR, 0.69) patients than for White patients.

“It’s possible that not all patients have equal access to information about these medications or that not all patients are equally comfortable asking their doctors about them,” lead author Luis A. Rodriguez, PhD, research scientist at Kaiser Permanente’s Northern California Division of Research, Oakland, told this news organization.

“We also don’t know if the cost of the new medications contributed to what we found or if some patients prefer to keep taking a pill rather than switch to some of the GLP-1 receptor agonists that are self-injectable medications. We need to learn more about why this is happening,” Dr. Rodriguez said.
 

‘Concerning’ Data Raise Key Questions

The third study explored how often prescribing recommendations for SGLT2 inhibitors are followed.

“Our study revealed a significant gap between the recommendations for prescribing SGLT2 inhibitors and the actual prescription rates among patients who could benefit from them,” Jung-Im Shin, MD, PhD, with the Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, told this news organization.

“This could have important implications for patient care and outcomes, as SGLT2 inhibitors have been shown to be effective for heart and kidney protection in people with high-risk type 2 diabetes, chronic kidney disease, or heart failure,” Dr. Shin said.

Dr. Shin and colleagues analyzed the health records for more than 700,000 adults with type 2 diabetes and 2.5 million people without type 2 diabetes, who received care in 28 US health systems from 2022 to 2023.

Among people with type 2 diabetes recommended for first-line SGLT2 inhibitors treatment, only 12% received a prescription for a SGLT2 inhibitor, and there was no significant difference in prescription between people who met the criteria for first-line SGLT2 inhibitors treatment vs people who did not meet the criteria.

Among people without type 2 diabetes, SGLT2 inhibitor prescription was substantially lower, with only about 3% of people with conditions that are guideline-recommended for SGLT2 inhibitors receiving a prescription.

SGLT2 inhibitor prescription rates varied across health systems; however, less than 30% of people who met guideline criteria received a SGLT2 inhibitors prescription across all health systems in the study.

“Barriers to SGLT2 inhibitor prescription include limited insurance coverage, prohibitive out-of-pocket costs, formulary restrictions, and lack of physicians’ awareness or familiarity regarding benefits and appropriate indications for SGLT2 inhibitors,” Dr. Shin said.

“Efforts to improve access and affordability of SGLT2 inhibitors along with strategies to educate both patients and providers on the updated guidelines for SGLT2 inhibitors use may increase adoption,” Dr. Shin added.

In a conference recording, Dr. Eckel said he found it “particularly concerning” that among patients with insurance to help pay for these medications, “there were still discrepancies” between prescriptions to Asian and Black vs White patients, “who are being prescribed these important medications.”

“Why these medications are not being offered more regularly by healthcare providers” needs to be addressed, Dr. Eckel said. “I think part of it is ignorance and inadequate education as to their new indications for treatment of diseases that go beyond type 2 diabetes,” he noted.

None of the studies had commercial funding. The authors had no relevant disclosures.

A version of this article appeared on Medscape.com.

Use of statin drugs was associated with improved mortality in older nursing home residents, regardless of dementia status, a new study showed.

The study is among the first to explore whether statin use in older nursing home residents offers a mortality benefit, especially among individuals with dementia, a group largely excluded from earlier statin trials.

Investigators’ analysis of 4 years of data on nearly 300,000 nursing home residents revealed that statin use was associated with a 40% lower risk for all-cause mortality than statin nonuse in those without dementia and a 20% lower risk in those with dementia.

“These findings may provide evidence that supports the continued use of statins in older nursing home patients with multiple medical conditions,” wrote lead author Julie Lorraine O’Sullivan, PhD, of the Charité–Universitätsmedizin Berlin, Freie Universität Berlin, German Center for Mental Health, Berlin, and colleagues.

The study was published online on February 27 in Neurology.
 

Understudied Population

Statins are the first-line treatment for preventing atherosclerotic cardiovascular disease (ASCVD), but they are also known to carry risks to patients who are frail or care-dependent. Many prior clinical trials excluded older participants with multiple comorbidities, especially those with dementia. So, evidence regarding the drugs’ efficacy in this population was lacking.

Investigators retrospectively examined 5 years of claims data from a German health and long-term care insurance provider on 282,693 nursing home residents (mean age, 83 years) who had used statins consecutively for ≥ 6 months.

Researchers used propensity score matching in 96,162 individuals to adjust for potential imbalances in the distribution of covariates (eg, age, sex, atrial fibrillation, ASCVD, and other conditions, as well as medications) and to reduce bias. Cox regression models were similarly adjusted for these factors, as well as care level. Residents were followed for an average of 2 years.

There were 54,269 recorded deaths during the study period, with most patients requiring a high level of care and 65% with dementia.

Statin use was associated with lower all-cause mortality in residents with dementia (hazard ratio [HR], 0.80, P < .001) and those without dementia (HR, 0.73; P < .001) compared with nonusers. The benefits remained consistent even after excluding participants with a history of ASCVD and across subgroups stratified by age sex, care level, and dementia type.

Limitations included the potential for unknown confounders and a lack of information about previous statin use, smoking and sedentary behavior, and the cause of mortality.

“Although our findings suggest the benefits of statins ... it is vital to acknowledge the need for further research to understand the underlying mechanism and the need for replication of our results to understand the potential risks before making recommendations to clinicians and families regarding statin therapy,” investigators wrote.
 

‘First Step’

In an accompanying editorial, Ariela R. Orkaby, MD, MPH, assistant professor of medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, called the study a “first step” to a better understanding of statin use in an understudied population.

“These findings build on a limited body of observational evidence for statin use in high-risk older adults, which has generally demonstrated protective associations for statins and mortality, including those with dementia and frailty, although nursing home status has not been specifically explored,” Dr. Orkaby wrote.

Perhaps more important than gaining information about statins’ effect on mortality risk in older people with dementia may be a better understanding of how the drugs might improve quality of life by reducing the risk for stroke or other cardiovascular events.

“It may be time to reconsider the broad recommendations to avoid or deprescribe statins in nursing home residents and rather invest in high-quality evidence to guide the care of this vulnerable population. After all, a lack of evidence does not imply benefit or harm, rather a need for more data,” Dr. Orkaby added.

The research was funded by Stiftung Charité; Dr. O’Sullivan and coauthors reported no relevant financial relationships. Dr. Orkaby received funding from a VA CSR&D CDA-2 award.
 

A version of this article appeared on Medscape.com.

Use of statin drugs was associated with improved mortality in older nursing home residents, regardless of dementia status, a new study showed.

The study is among the first to explore whether statin use in older nursing home residents offers a mortality benefit, especially among individuals with dementia, a group largely excluded from earlier statin trials.

Investigators’ analysis of 4 years of data on nearly 300,000 nursing home residents revealed that statin use was associated with a 40% lower risk for all-cause mortality than statin nonuse in those without dementia and a 20% lower risk in those with dementia.

“These findings may provide evidence that supports the continued use of statins in older nursing home patients with multiple medical conditions,” wrote lead author Julie Lorraine O’Sullivan, PhD, of the Charité–Universitätsmedizin Berlin, Freie Universität Berlin, German Center for Mental Health, Berlin, and colleagues.

The study was published online on February 27 in Neurology.
 

Understudied Population

Statins are the first-line treatment for preventing atherosclerotic cardiovascular disease (ASCVD), but they are also known to carry risks to patients who are frail or care-dependent. Many prior clinical trials excluded older participants with multiple comorbidities, especially those with dementia. So, evidence regarding the drugs’ efficacy in this population was lacking.

Investigators retrospectively examined 5 years of claims data from a German health and long-term care insurance provider on 282,693 nursing home residents (mean age, 83 years) who had used statins consecutively for ≥ 6 months.

Researchers used propensity score matching in 96,162 individuals to adjust for potential imbalances in the distribution of covariates (eg, age, sex, atrial fibrillation, ASCVD, and other conditions, as well as medications) and to reduce bias. Cox regression models were similarly adjusted for these factors, as well as care level. Residents were followed for an average of 2 years.

There were 54,269 recorded deaths during the study period, with most patients requiring a high level of care and 65% with dementia.

Statin use was associated with lower all-cause mortality in residents with dementia (hazard ratio [HR], 0.80, P < .001) and those without dementia (HR, 0.73; P < .001) compared with nonusers. The benefits remained consistent even after excluding participants with a history of ASCVD and across subgroups stratified by age sex, care level, and dementia type.

Limitations included the potential for unknown confounders and a lack of information about previous statin use, smoking and sedentary behavior, and the cause of mortality.

“Although our findings suggest the benefits of statins ... it is vital to acknowledge the need for further research to understand the underlying mechanism and the need for replication of our results to understand the potential risks before making recommendations to clinicians and families regarding statin therapy,” investigators wrote.
 

‘First Step’

In an accompanying editorial, Ariela R. Orkaby, MD, MPH, assistant professor of medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, called the study a “first step” to a better understanding of statin use in an understudied population.

“These findings build on a limited body of observational evidence for statin use in high-risk older adults, which has generally demonstrated protective associations for statins and mortality, including those with dementia and frailty, although nursing home status has not been specifically explored,” Dr. Orkaby wrote.

Perhaps more important than gaining information about statins’ effect on mortality risk in older people with dementia may be a better understanding of how the drugs might improve quality of life by reducing the risk for stroke or other cardiovascular events.

“It may be time to reconsider the broad recommendations to avoid or deprescribe statins in nursing home residents and rather invest in high-quality evidence to guide the care of this vulnerable population. After all, a lack of evidence does not imply benefit or harm, rather a need for more data,” Dr. Orkaby added.

The research was funded by Stiftung Charité; Dr. O’Sullivan and coauthors reported no relevant financial relationships. Dr. Orkaby received funding from a VA CSR&D CDA-2 award.
 

A version of this article appeared on Medscape.com.

Use of statin drugs was associated with improved mortality in older nursing home residents, regardless of dementia status, a new study showed.

The study is among the first to explore whether statin use in older nursing home residents offers a mortality benefit, especially among individuals with dementia, a group largely excluded from earlier statin trials.

Investigators’ analysis of 4 years of data on nearly 300,000 nursing home residents revealed that statin use was associated with a 40% lower risk for all-cause mortality than statin nonuse in those without dementia and a 20% lower risk in those with dementia.

“These findings may provide evidence that supports the continued use of statins in older nursing home patients with multiple medical conditions,” wrote lead author Julie Lorraine O’Sullivan, PhD, of the Charité–Universitätsmedizin Berlin, Freie Universität Berlin, German Center for Mental Health, Berlin, and colleagues.

The study was published online on February 27 in Neurology.
 

Understudied Population

Statins are the first-line treatment for preventing atherosclerotic cardiovascular disease (ASCVD), but they are also known to carry risks to patients who are frail or care-dependent. Many prior clinical trials excluded older participants with multiple comorbidities, especially those with dementia. So, evidence regarding the drugs’ efficacy in this population was lacking.

Investigators retrospectively examined 5 years of claims data from a German health and long-term care insurance provider on 282,693 nursing home residents (mean age, 83 years) who had used statins consecutively for ≥ 6 months.

Researchers used propensity score matching in 96,162 individuals to adjust for potential imbalances in the distribution of covariates (eg, age, sex, atrial fibrillation, ASCVD, and other conditions, as well as medications) and to reduce bias. Cox regression models were similarly adjusted for these factors, as well as care level. Residents were followed for an average of 2 years.

There were 54,269 recorded deaths during the study period, with most patients requiring a high level of care and 65% with dementia.

Statin use was associated with lower all-cause mortality in residents with dementia (hazard ratio [HR], 0.80, P < .001) and those without dementia (HR, 0.73; P < .001) compared with nonusers. The benefits remained consistent even after excluding participants with a history of ASCVD and across subgroups stratified by age sex, care level, and dementia type.

Limitations included the potential for unknown confounders and a lack of information about previous statin use, smoking and sedentary behavior, and the cause of mortality.

“Although our findings suggest the benefits of statins ... it is vital to acknowledge the need for further research to understand the underlying mechanism and the need for replication of our results to understand the potential risks before making recommendations to clinicians and families regarding statin therapy,” investigators wrote.
 

‘First Step’

In an accompanying editorial, Ariela R. Orkaby, MD, MPH, assistant professor of medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, called the study a “first step” to a better understanding of statin use in an understudied population.

“These findings build on a limited body of observational evidence for statin use in high-risk older adults, which has generally demonstrated protective associations for statins and mortality, including those with dementia and frailty, although nursing home status has not been specifically explored,” Dr. Orkaby wrote.

Perhaps more important than gaining information about statins’ effect on mortality risk in older people with dementia may be a better understanding of how the drugs might improve quality of life by reducing the risk for stroke or other cardiovascular events.

“It may be time to reconsider the broad recommendations to avoid or deprescribe statins in nursing home residents and rather invest in high-quality evidence to guide the care of this vulnerable population. After all, a lack of evidence does not imply benefit or harm, rather a need for more data,” Dr. Orkaby added.

The research was funded by Stiftung Charité; Dr. O’Sullivan and coauthors reported no relevant financial relationships. Dr. Orkaby received funding from a VA CSR&D CDA-2 award.
 

A version of this article appeared on Medscape.com.