Acute Coronary Syndromes

Beta-blockers are excellent drugs. They’re cheap and effective; feature prominently in hypertension guidelines; and remain a sine qua non for coronary artery disease, myocardial infarction, and heart failure treatment. They’ve been around forever, and we know they work. Good luck finding an adult medicine patient who isn’t on one.

Beta-blockers act by slowing resting heart rate (and blunting the heart rate response to exercise. The latter is a pernicious cause of activity intolerance that often goes unchecked. Even when the adverse effects of beta-blockers are appreciated, providers are loath to alter dosing, much less stop the drug. After all, beta-blockers are an integral part of guideline-directed medical therapy (GDMT), and GDMT saves lives.

Balancing Heart Rate and Stroke Volume Effects

The pulmonologist sees beta-blockers differently. To augment cardiac output and optimize oxygen uptake (VO₂) during exercise, we need the heart rate response. In fact, the heart rate response contributes more to cardiac output than augmenting stroke volume (SV) and more to VO₂ than the increase in arteriovenous (AV) oxygen difference. An inability to increase the heart rate commensurate with physiologic work is called chronotropic incompetence (CI). That’s what beta-blockers do ─ they cause CI.

Physiology dictates that CI will cause activity intolerance. That said, it’s hard to quantify the impact from beta-blockers at the individual patient level. Data suggest the heart rate effect is profound. A study in patients without heart failure found that 22% of participants on beta-blockers had CI, and the investigators used a conservative CI definition (≤ 62% of heart rate reserve used). A recent report published in JAMA Cardiology found that stopping beta-blockers in patients with heart failure allowed for an extra 30 beats/min at max exercise.

Wasserman and Whipp’s textbook, the last word on all things exercise, presents a sample subject who undergoes two separate cardiopulmonary exercise tests (CPETs). Before the first, he’s given a placebo, and before the second, he gets an intravenous beta-blocker. He’s a 23-year-old otherwise healthy male — the perfect test case for isolating beta-blocker impact without confounding by comorbid diseases, other medications, or deconditioning. His max heart rate dropped by 30 beats/min after the beta-blocker, identical to what we saw in the JAMA Cardiology study (with the heart rate increasing by 30 beats/min following withdrawal). Case closed. Stop the beta-blockers on your patients so they can meet their exercise goals and get healthy!

Such pithy enthusiasm discounts physiology’s complexities. When blunting our patient’s heart rate response with beta-blockers, we also increase diastolic filling time, which increases SV. For the 23-year-old in Wasserman and Whipp’s physiology textbook, the beta-blocker increased O₂ pulse (the product of SV and AV difference). Presumably, this is mediated by the increased SV. There was a net reduction in VO₂ peak, but it was nominal, suggesting that the drop in heart rate was largely offset by the increase in O₂ pulse. For the patients in the JAMA Cardiology study, the entire group had a small increase in VO2 peak with beta-blocker withdrawal, but the effect differed by left ventricular function. Across different studies, the beta-blocker effect on heart rate is consistent but the change in overall exercise capacity is not. 

Patient Variability in Beta-Blocker Response

In addition to left ventricular function, there are other factors likely to drive variability at the patient level. We’ve treated the response to beta-blockers as a class effect — an obvious oversimplification. The impact on exercise and the heart will vary by dose and drug (eg, atenolol vs metoprolol vs carvedilol, and so on). Beta-blockers can also affect the lungs, and we’re still debating how cautious to be in the presence of asthma or chronic obstructive pulmonary disease. 

In a world of infinite time, resources, and expertise, we’d CPET everyone before and after beta-blocker use. Our current reality requires the unthinkable: We’ll have to talk to each other and our patients. For example, heart failure guidelines recommend titrating drugs to match the dose from trials that proved efficacy. These doses are quite high. Simple discussion with the cardiologist and the patient may allow for an adjustment back down with careful monitoring and close attention to activity tolerance. With any luck, you’ll preserve the benefits from GDMT while optimizing your patient›s ability to meet their exercise goals.
 

Dr. Holley, professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center, Washington, disclosed ties with Metapharm, CHEST College, and WebMD.

A version of this article appeared on Medscape.com.

Beta-blockers are excellent drugs. They’re cheap and effective; feature prominently in hypertension guidelines; and remain a sine qua non for coronary artery disease, myocardial infarction, and heart failure treatment. They’ve been around forever, and we know they work. Good luck finding an adult medicine patient who isn’t on one.

Beta-blockers act by slowing resting heart rate (and blunting the heart rate response to exercise. The latter is a pernicious cause of activity intolerance that often goes unchecked. Even when the adverse effects of beta-blockers are appreciated, providers are loath to alter dosing, much less stop the drug. After all, beta-blockers are an integral part of guideline-directed medical therapy (GDMT), and GDMT saves lives.

Balancing Heart Rate and Stroke Volume Effects

The pulmonologist sees beta-blockers differently. To augment cardiac output and optimize oxygen uptake (VO₂) during exercise, we need the heart rate response. In fact, the heart rate response contributes more to cardiac output than augmenting stroke volume (SV) and more to VO₂ than the increase in arteriovenous (AV) oxygen difference. An inability to increase the heart rate commensurate with physiologic work is called chronotropic incompetence (CI). That’s what beta-blockers do ─ they cause CI.

Physiology dictates that CI will cause activity intolerance. That said, it’s hard to quantify the impact from beta-blockers at the individual patient level. Data suggest the heart rate effect is profound. A study in patients without heart failure found that 22% of participants on beta-blockers had CI, and the investigators used a conservative CI definition (≤ 62% of heart rate reserve used). A recent report published in JAMA Cardiology found that stopping beta-blockers in patients with heart failure allowed for an extra 30 beats/min at max exercise.

Wasserman and Whipp’s textbook, the last word on all things exercise, presents a sample subject who undergoes two separate cardiopulmonary exercise tests (CPETs). Before the first, he’s given a placebo, and before the second, he gets an intravenous beta-blocker. He’s a 23-year-old otherwise healthy male — the perfect test case for isolating beta-blocker impact without confounding by comorbid diseases, other medications, or deconditioning. His max heart rate dropped by 30 beats/min after the beta-blocker, identical to what we saw in the JAMA Cardiology study (with the heart rate increasing by 30 beats/min following withdrawal). Case closed. Stop the beta-blockers on your patients so they can meet their exercise goals and get healthy!

Such pithy enthusiasm discounts physiology’s complexities. When blunting our patient’s heart rate response with beta-blockers, we also increase diastolic filling time, which increases SV. For the 23-year-old in Wasserman and Whipp’s physiology textbook, the beta-blocker increased O₂ pulse (the product of SV and AV difference). Presumably, this is mediated by the increased SV. There was a net reduction in VO₂ peak, but it was nominal, suggesting that the drop in heart rate was largely offset by the increase in O₂ pulse. For the patients in the JAMA Cardiology study, the entire group had a small increase in VO2 peak with beta-blocker withdrawal, but the effect differed by left ventricular function. Across different studies, the beta-blocker effect on heart rate is consistent but the change in overall exercise capacity is not. 

Patient Variability in Beta-Blocker Response

In addition to left ventricular function, there are other factors likely to drive variability at the patient level. We’ve treated the response to beta-blockers as a class effect — an obvious oversimplification. The impact on exercise and the heart will vary by dose and drug (eg, atenolol vs metoprolol vs carvedilol, and so on). Beta-blockers can also affect the lungs, and we’re still debating how cautious to be in the presence of asthma or chronic obstructive pulmonary disease. 

In a world of infinite time, resources, and expertise, we’d CPET everyone before and after beta-blocker use. Our current reality requires the unthinkable: We’ll have to talk to each other and our patients. For example, heart failure guidelines recommend titrating drugs to match the dose from trials that proved efficacy. These doses are quite high. Simple discussion with the cardiologist and the patient may allow for an adjustment back down with careful monitoring and close attention to activity tolerance. With any luck, you’ll preserve the benefits from GDMT while optimizing your patient›s ability to meet their exercise goals.
 

Dr. Holley, professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center, Washington, disclosed ties with Metapharm, CHEST College, and WebMD.

A version of this article appeared on Medscape.com.

Beta-blockers are excellent drugs. They’re cheap and effective; feature prominently in hypertension guidelines; and remain a sine qua non for coronary artery disease, myocardial infarction, and heart failure treatment. They’ve been around forever, and we know they work. Good luck finding an adult medicine patient who isn’t on one.

Beta-blockers act by slowing resting heart rate (and blunting the heart rate response to exercise. The latter is a pernicious cause of activity intolerance that often goes unchecked. Even when the adverse effects of beta-blockers are appreciated, providers are loath to alter dosing, much less stop the drug. After all, beta-blockers are an integral part of guideline-directed medical therapy (GDMT), and GDMT saves lives.

Balancing Heart Rate and Stroke Volume Effects

The pulmonologist sees beta-blockers differently. To augment cardiac output and optimize oxygen uptake (VO₂) during exercise, we need the heart rate response. In fact, the heart rate response contributes more to cardiac output than augmenting stroke volume (SV) and more to VO₂ than the increase in arteriovenous (AV) oxygen difference. An inability to increase the heart rate commensurate with physiologic work is called chronotropic incompetence (CI). That’s what beta-blockers do ─ they cause CI.

Physiology dictates that CI will cause activity intolerance. That said, it’s hard to quantify the impact from beta-blockers at the individual patient level. Data suggest the heart rate effect is profound. A study in patients without heart failure found that 22% of participants on beta-blockers had CI, and the investigators used a conservative CI definition (≤ 62% of heart rate reserve used). A recent report published in JAMA Cardiology found that stopping beta-blockers in patients with heart failure allowed for an extra 30 beats/min at max exercise.

Wasserman and Whipp’s textbook, the last word on all things exercise, presents a sample subject who undergoes two separate cardiopulmonary exercise tests (CPETs). Before the first, he’s given a placebo, and before the second, he gets an intravenous beta-blocker. He’s a 23-year-old otherwise healthy male — the perfect test case for isolating beta-blocker impact without confounding by comorbid diseases, other medications, or deconditioning. His max heart rate dropped by 30 beats/min after the beta-blocker, identical to what we saw in the JAMA Cardiology study (with the heart rate increasing by 30 beats/min following withdrawal). Case closed. Stop the beta-blockers on your patients so they can meet their exercise goals and get healthy!

Such pithy enthusiasm discounts physiology’s complexities. When blunting our patient’s heart rate response with beta-blockers, we also increase diastolic filling time, which increases SV. For the 23-year-old in Wasserman and Whipp’s physiology textbook, the beta-blocker increased O₂ pulse (the product of SV and AV difference). Presumably, this is mediated by the increased SV. There was a net reduction in VO₂ peak, but it was nominal, suggesting that the drop in heart rate was largely offset by the increase in O₂ pulse. For the patients in the JAMA Cardiology study, the entire group had a small increase in VO2 peak with beta-blocker withdrawal, but the effect differed by left ventricular function. Across different studies, the beta-blocker effect on heart rate is consistent but the change in overall exercise capacity is not. 

Patient Variability in Beta-Blocker Response

In addition to left ventricular function, there are other factors likely to drive variability at the patient level. We’ve treated the response to beta-blockers as a class effect — an obvious oversimplification. The impact on exercise and the heart will vary by dose and drug (eg, atenolol vs metoprolol vs carvedilol, and so on). Beta-blockers can also affect the lungs, and we’re still debating how cautious to be in the presence of asthma or chronic obstructive pulmonary disease. 

In a world of infinite time, resources, and expertise, we’d CPET everyone before and after beta-blocker use. Our current reality requires the unthinkable: We’ll have to talk to each other and our patients. For example, heart failure guidelines recommend titrating drugs to match the dose from trials that proved efficacy. These doses are quite high. Simple discussion with the cardiologist and the patient may allow for an adjustment back down with careful monitoring and close attention to activity tolerance. With any luck, you’ll preserve the benefits from GDMT while optimizing your patient›s ability to meet their exercise goals.
 

Dr. Holley, professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center, Washington, disclosed ties with Metapharm, CHEST College, and WebMD.

A version of this article appeared on Medscape.com.

HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.

A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.

“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.

“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.

They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
 

Independent Risk Factor

The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.

This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.

Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.

Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).

They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).

The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.

In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.

“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.

They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.

“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.

“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
 

Compelling Evidence for Higher CVD

Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.

“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.

“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.

Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.

“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.

The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.

A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.

“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.

“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.

They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
 

Independent Risk Factor

The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.

This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.

Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.

Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).

They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).

The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.

In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.

“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.

They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.

“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.

“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
 

Compelling Evidence for Higher CVD

Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.

“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.

“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.

Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.

“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.

The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.

A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.

“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.

“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.

They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
 

Independent Risk Factor

The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.

This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.

Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.

Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).

They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).

The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.

In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.

“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.

They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.

“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.

“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
 

Compelling Evidence for Higher CVD

Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.

“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.

“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.

Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.

“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.

The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.

A version of this article appeared on Medscape.com.

High levels of xylitol, a low-calorie sweetener used in many reduced-sugar foods as well as gum and toothpaste, are linked to an increased risk of heart attacks, strokes, and death, says a new study published in the European Heart Journal.

The research team studied more than 3000 people in the US and Europe over 3 years and found that people with the highest amount of xylitol in their plasma were more likely to have a problem with their heart or blood vessels.

To show the early effects of xylitol, researchers studied platelet activity in volunteers who consumed a xylitol-sweetened drink and a glucose-sweetened drink. The xylitol levels went up by 1000 times in people after the xylitol drink but not after the glucose-sweetened drink.

Xylitol is naturally found in small amounts in fruit and vegetables, and it’s been used more as a sugar substitute over the past decade in processed foods, toothpaste, chewing gum, and other products.

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” Stanley Hazen, MD, chair of the Department of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute, Cleveland, Ohio, said in a news release.

“It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot-related events.”

A similar link between erythritol, another sugar substance, and problems with the heart and blood vessels was found last year by the same research team, the release said.

In a response to the study, the Calorie Control Council, a trade association representing the low- and reduced-calorie food and beverage industry, said xylitol has been approved for decades by government agencies. The study results may not apply to the general population because some people in the study already had a higher risk of having problems with their heart and blood vessels, it said.

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

High levels of xylitol, a low-calorie sweetener used in many reduced-sugar foods as well as gum and toothpaste, are linked to an increased risk of heart attacks, strokes, and death, says a new study published in the European Heart Journal.

The research team studied more than 3000 people in the US and Europe over 3 years and found that people with the highest amount of xylitol in their plasma were more likely to have a problem with their heart or blood vessels.

To show the early effects of xylitol, researchers studied platelet activity in volunteers who consumed a xylitol-sweetened drink and a glucose-sweetened drink. The xylitol levels went up by 1000 times in people after the xylitol drink but not after the glucose-sweetened drink.

Xylitol is naturally found in small amounts in fruit and vegetables, and it’s been used more as a sugar substitute over the past decade in processed foods, toothpaste, chewing gum, and other products.

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” Stanley Hazen, MD, chair of the Department of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute, Cleveland, Ohio, said in a news release.

“It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot-related events.”

A similar link between erythritol, another sugar substance, and problems with the heart and blood vessels was found last year by the same research team, the release said.

In a response to the study, the Calorie Control Council, a trade association representing the low- and reduced-calorie food and beverage industry, said xylitol has been approved for decades by government agencies. The study results may not apply to the general population because some people in the study already had a higher risk of having problems with their heart and blood vessels, it said.

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

High levels of xylitol, a low-calorie sweetener used in many reduced-sugar foods as well as gum and toothpaste, are linked to an increased risk of heart attacks, strokes, and death, says a new study published in the European Heart Journal.

The research team studied more than 3000 people in the US and Europe over 3 years and found that people with the highest amount of xylitol in their plasma were more likely to have a problem with their heart or blood vessels.

To show the early effects of xylitol, researchers studied platelet activity in volunteers who consumed a xylitol-sweetened drink and a glucose-sweetened drink. The xylitol levels went up by 1000 times in people after the xylitol drink but not after the glucose-sweetened drink.

Xylitol is naturally found in small amounts in fruit and vegetables, and it’s been used more as a sugar substitute over the past decade in processed foods, toothpaste, chewing gum, and other products.

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” Stanley Hazen, MD, chair of the Department of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute, Cleveland, Ohio, said in a news release.

“It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot-related events.”

A similar link between erythritol, another sugar substance, and problems with the heart and blood vessels was found last year by the same research team, the release said.

In a response to the study, the Calorie Control Council, a trade association representing the low- and reduced-calorie food and beverage industry, said xylitol has been approved for decades by government agencies. The study results may not apply to the general population because some people in the study already had a higher risk of having problems with their heart and blood vessels, it said.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

TOPLINE:

Arterial stiffness increases the risk for developing glaucoma, a new study found.

METHODOLOGY:

• To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
• They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
• The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.

TAKEAWAY:

• Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
• For every standard deviation increase in aortic pulse wave velocity, participants had a 32% higher risk for developing glaucoma (standardized hazard ratio [sHR], 1.32; 95% CI, 1.10-1.60), while estimated carotid-femoral pulse wave velocity was associated with a 37% higher risk (sHR, 1.37; 95% CI, 1.11-1.70).
• Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
• The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).

IN PRACTICE:

“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.

SOURCE:

This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.

LIMITATIONS:

The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Arterial stiffness increases the risk for developing glaucoma, a new study found.

METHODOLOGY:

• To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
• They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
• The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.

TAKEAWAY:

• Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
• For every standard deviation increase in aortic pulse wave velocity, participants had a 32% higher risk for developing glaucoma (standardized hazard ratio [sHR], 1.32; 95% CI, 1.10-1.60), while estimated carotid-femoral pulse wave velocity was associated with a 37% higher risk (sHR, 1.37; 95% CI, 1.11-1.70).
• Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
• The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).

IN PRACTICE:

“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.

SOURCE:

This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.

LIMITATIONS:

The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Arterial stiffness increases the risk for developing glaucoma, a new study found.

METHODOLOGY:

• To study the link between arterial stiffness and glaucoma, the researchers evaluated 4713 individuals (mean age, 66 years; 58% men) without the eye condition at baseline between April 2011 and November 2012.
• They assessed arterial stiffness by measuring aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure.
• The primary outcome was incident glaucoma, identified from prescriptions for eye drops or hospital records.

TAKEAWAY:

• Overall, 301 people in the study developed glaucoma over a mean follow-up period of 10.5 years.
• For every standard deviation increase in aortic pulse wave velocity, participants had a 32% higher risk for developing glaucoma (standardized hazard ratio [sHR], 1.32; 95% CI, 1.10-1.60), while estimated carotid-femoral pulse wave velocity was associated with a 37% higher risk (sHR, 1.37; 95% CI, 1.11-1.70).
• Incident glaucoma increased across all quartiles of arterial stiffness, with the highest risk observed in the fourth quartile for aortic pulse wave velocity (HR, 2.41; 95% CI, 1.36-4.26), estimated carotid-femoral pulse wave velocity (HR, 2.29; 95% CI, 1.27-4.13), and aortic pulse pressure (HR, 1.76; 95% CI, 1.10-2.82).
• The cumulative incidence of glaucoma rose with increases in arterial stiffness. This trend was statistically significant for both aortic and estimated pulse wave velocity (P < .0001) and aortic pulse pressure (P = .02).

IN PRACTICE:

“Arterial stiffness…which can be easily and accurately measured, could be used as a tool in clinical practice [as part of routine blood pressure measurement] to help identify people at risk of glaucoma and as a therapeutic target to prevent glaucoma progression,” the authors wrote.

SOURCE:

This study was led by Angela L. Beros, MPH, of the School of Population Health at the University of Auckland, Auckland, New Zealand, and published online in the American Journal of Ophthalmology.

LIMITATIONS:

The cohort study did not clinically assess for glaucoma, potentially leading to the inclusion of individuals with the condition. Not all participants with incident glaucoma, particularly those unaware of their diagnosis, may have been identified. Intraocular pressure and central corneal thickness, which are common risk factors for glaucoma, were not included in the multivariate analysis.

DISCLOSURES:

The study did not receive any funding. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”

The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.

“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.

Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.

“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.

The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.

The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.

Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.

Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.

Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.

During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.

Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.

This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.

“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”

*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.

*This study was updated on May 30, 2024.

SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”

The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.

“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.

Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.

“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.

The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.

The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.

Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.

Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.

Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.

During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.

Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.

This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.

“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”

*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.

*This study was updated on May 30, 2024.

SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”

The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.

“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.

Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.

“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.

The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.

The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.

Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.

Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.

Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.

During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.

Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.

This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.

“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”

*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.

*This study was updated on May 30, 2024.

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

According to a US cross-sectional study, every fifth hospital patient with a respiratory syncytial virus (RSV) infection develops an acute cardiovascular event. For patients with a preexisting cardiovascular condition, an acute cardiovascular event occurs in every third patient, as shown by data published in JAMA Internal Medicine.

RSV attacks the respiratory tract, especially the mucous membranes of the upper airways and the ciliated epithelium of the trachea and bronchi. It is not the first respiratory virus with devastating consequences for the cardiovascular system.

“In the COVID-19 pandemic, we painfully learned that patients with preexisting cardiovascular conditions have significantly higher mortality rates and that cardiovascular causes are essential in COVID-19 mortality,” said Stephan Baldus, MD, director of Clinic III for Internal Medicine at the Heart Center of the University Hospital Cologne in Cologne, Germany.

“A direct link between the virus and the development of acute coronary events has also been demonstrated for influenza. Studies have shown that in the early days of an influenza infection, the rates of heart attacks and subsequent deaths increase significantly,” Dr. Baldus added. “And now, this study shows that patients with cardiovascular diseases have a critically increased risk for an acute cardiovascular event during an RSV infection.”
 

RSV Surveillance

Rebecca C. Woodruff, PhD, of the Centers for Disease Control and Prevention in Atlanta, and her colleagues analyzed data from an RSV surveillance program involving hospitals in 12 US states. The data covered hospitalized adults aged 50 years and older from five RSV seasons (from 2014/2015 to 2017/2018 and 2022/2023).

The 6248 patients were hospitalized for various reasons. They had a mean age of 73 years, and 60% of them were women. RSV infection was detected through a physician-ordered test within 14 days of admission. Slightly more than half (56.4%) of the patients had a preexisting cardiovascular condition that did not necessitate hospital treatment.

The researchers reported that more than a fifth (22.4%) of the patients with RSV had an acute cardiovascular event. Acute heart failure was most common (15.8%), but there were also acute ischemic heart disease in 7.5%, hypertensive crisis in 1.3%, ventricular tachycardia in 1.1%, and cardiogenic shock in 0.6%.
 

Acute Cardiovascular Events

Among the study population, 8.5% had no documented cardiovascular preexisting conditions. However, the risk was particularly elevated in patients with cardiovascular preexisting conditions. Overall, 33.0% of them had an acute cardiovascular event during the RSV infection.

Patients with acute cardiovascular events were almost twice as likely to have a severe course as those without acute cardiovascular events. The researchers considered treatment in the intensive care unit, the need for invasive mechanical ventilation, or the patient’s death in the hospital as severe outcomes.

Of all hospitalized patients with RSV, 18.6% required intensive care unit treatment, and 4.9% died during hospitalization. Compared with those without acute cardiovascular events, those with acute cardiovascular events had a significantly higher risk for intensive care treatment (25.8% vs 16.5%) and death in the hospital (8.1% vs 4.0%).

Although the analysis is not a prospective controlled study, according to Dr. Baldus, the results strongly suggest that RSV has cardiovascular effects. “When one in five hospitalized patients develops a cardiovascular event, that’s very suggestive,” he said.
 

More Testing Needed?

The results add to the evidence that RSV infections in older patients are associated with considerable morbidity and mortality. Unlike for COVID-19 and influenza, however, there is hardly any surveillance for RSV infections. RSV testing in hospitals is rare. Many doctors opt against testing for RSV because they are not aware of the importance of RSV as a pathogen in adults, but also because the diagnosis of RSV has no therapeutic consequences, wrote Dr. Woodruff and her colleagues.

Because there is no targeted therapy for an RSV infection, the detection of RSV can only be used as a marker for a risk for the development of an acute cardiovascular event, according to Dr. Baldus. Even considering the new study data, he emphasized, “Not every patient with a cardiovascular preexisting condition needs to be tested for RSV.”

The crucial factor is the clinical presentation. “If there is a clinical indication of pulmonary impairment (shortness of breath, tachypnea, subfebrile temperatures, or a diminished general condition) it would be desirable to perform an RSV test. This is especially true for patients requiring intensive care who need respiratory support,” said Dr. Baldus.
 

Benefits of Vaccination

The results highlight the basic epidemiology of potential cardiovascular complications of RSV infections, but before RSV vaccination became available, wrote Dr. Woodruff and her colleagues.

In 2023, the first RSV vaccine for adults aged 60 years and older was approved. “Here, a door to additional possibilities opens,” said Dr. Baldus. Although there are currently no official vaccination recommendations from Germany’s Standing Vaccination Commission, medical societies of oncologists and pulmonologists recommend vaccination against RSV. “Given the relevance of cardiovascular diseases for the prognosis of patients, but also for the occurrence of an acute cardiovascular event upon detection of RSV, the corresponding recommendation is expected to come,” said Dr. Baldus.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.

In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval^® by Merril Life Sciences and compared them with the balloon-expandable Sapien^® from Edwards Lifesciences and the self-expanding Evolut^® valve from Medtronic.

The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.

The platform with intermediate sizes provided a nonsignificant numerical advantage in both safety and efficacy over its rivals, Patrick W. Serruys, MD, PhD, from the Department of Cardiology at the University of Galway in Galway, Ireland, reported at the Congress of the European Association of Percutaneous Coronary Interventions 2024.

The LANDMARK Trial

The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.

Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.

The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.

Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.

For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.

When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms. 

Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.

Precise Matching

The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.

The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.

Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.

However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.

Longer Follow-Up to Come

Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.

Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”

And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.

A version of this article appeared on Medscape.com.

PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.

In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval^® by Merril Life Sciences and compared them with the balloon-expandable Sapien^® from Edwards Lifesciences and the self-expanding Evolut^® valve from Medtronic.

The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.

The platform with intermediate sizes provided a nonsignificant numerical advantage in both safety and efficacy over its rivals, Patrick W. Serruys, MD, PhD, from the Department of Cardiology at the University of Galway in Galway, Ireland, reported at the Congress of the European Association of Percutaneous Coronary Interventions 2024.

The LANDMARK Trial

The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.

Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.

The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.

Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.

For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.

When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms. 

Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.

Precise Matching

The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.

The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.

Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.

However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.

Longer Follow-Up to Come

Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.

Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”

And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.

A version of this article appeared on Medscape.com.

PARIS — Intermediate valve sizes are at least as safe and effective as the standard sizes now available for transcatheter aortic valve implantation (TAVI), according to an international randomized trial.

In a head-to-head comparison, the LANDMARK trial looked at valves from the new balloon-expandable Myval^® by Merril Life Sciences and compared them with the balloon-expandable Sapien^® from Edwards Lifesciences and the self-expanding Evolut^® valve from Medtronic.

The new Myval platform offers multiple valves sized at 1.5 mm intervals, while the other two have valves that are generally sized at intervals of 3.0 mm.

The platform with intermediate sizes provided a nonsignificant numerical advantage in both safety and efficacy over its rivals, Patrick W. Serruys, MD, PhD, from the Department of Cardiology at the University of Galway in Galway, Ireland, reported at the Congress of the European Association of Percutaneous Coronary Interventions 2024.

The LANDMARK Trial

The trial enrolled 768 patients at 31 sites in 16 countries. They were randomized in a 1:1 fashion to the new platform or to one of the standards to compare the concept of intermediate valves with contemporary standards.

Seven sizes of Myval valves were used in the study, ranging from 20 mm to 29 mm at 1.5 mm increments. Two more sizes, 30.5 mm and 32.0 mm, were not included in this analysis but are being following in a registry.

The study also used Sapien valves sized 20 mm, 23 mm, 26 mm, and 29 mm and Evolut valves sized 26 mm, 29 mm, and 34 mm. There is also a 23 mm Evolut valve available, but it was not selected by any of the participating investigators.

Of the 336 patients given Myval valves, 48% were an intermediate size not available on one of the other platforms.

For the primary composite efficacy and safety endpoint of all-cause mortality, fatal or nonfatal strokes, VARC 3 or 4 bleeding, acute kidney injury, major vascular injury, moderate or greater valve regurgitation, or conduction disturbances requiring a new permanent pacemaker, the difference in absolute risk was slightly lower in the Myval arm, at 24.7% vs 27.0%, but not statistically significant. With that numerical difference favoring the Myval platform, noninferiority was demonstrated at 30 days with a high level of statistical significance, Dr. Serruys reported.

When each endpoint, with the composite primary endpoint, was evaluated separately in a secondary analysis, all-cause mortality and stroke incidence were identical in the two arms. 

Major bleeding and acute kidney injury were nonsignificantly more common in the Myval group, while the incidence of moderate or greater valve regurgitation, placement of a new permanent pacemaker, and major vascular complications were nonsignificantly less common.

Precise Matching

The effective orifice area was consistently higher in the group receiving an intermediate valve relative to a Sapien valve. This was not significant for the 20 mm valve size, but it did reach statistical significance for the rest of the sizes. In contrast, there was no significant difference with the Evolut series.

The data suggest that intermediate sizes “enable precise and appropriate matching of devices to an individual anatomy,” at least relative to Sapien, said Dr. Serruys.

Martin Leon, MD, of Columbia University in New York, called LANDMARK an important step for considering how comparative trials should be conducted in the future.

However, he challenged the idea that this study compared devices for both safety and efficacy. Despite the evidence it provides on device and procedural safety over the short-term, he said few conclusions can be drawn about comparative efficacy after just 30 days. Rather, the true comparative value of the trial will be derived from “rigorous late follow-up,” he said.

Longer Follow-Up to Come

Dr. Serruys acknowledged that the differences seen after 30 days have uncertain relevance to longer-term outcomes. He is planning to conduct a 10-year follow-up that “will unravel whether the documented effective orifice area of the Myval platform will have a beneficial impact on long-term patient prognosis and valve durability,” he said.

Leon agreed that, so far, these data do suggest superior hemodynamic performance with the intermediate sizing relative to valves in the Sapien platform, but the same cannot be said for the Evolut platform, and he pointed out that pooling data from the two platforms for the primary endpoint “makes comparisons difficult.”

And with about half of patients still fitted with the sizes already available, he said a deeper understanding was needed of how “adjustment strategies,” such as oversizing, affect long-term outcomes relative to platforms, such as Myval, with more valve sizes.

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.

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.

Shah_Binita_NY_web.jpg

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.

Garshick_Michael_NY_web.JPG

“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.

Shah_Binita_NY_web.jpg

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.

Garshick_Michael_NY_web.JPG

“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.

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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.

Garshick_Michael_NY_web.JPG

“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 .