Cardiology News

I’d like to talk with you about a recent report in the British Medical Journal on the regular use of omega-3 fish oil supplements and the course of cardiovascular disease (CVD).

This is an observational study from the large-scale UK Biobank. The authors divided the participants into those with and those without CVD. In participants without CVD at baseline, those using fish oil supplements regularly had an increased incidence of both atrial fibrillation (AF) and stroke, whereas those with prevalent CVD had a reduction in the progression to major adverse cardiovascular events, which offset any increase in the risk for AF.

Observational studies of omega-3 supplements have potential limitations and confounding, and correlation in these studies does not prove causation. What do the randomized clinical trials of omega-3 supplements show? At least seven randomized trials have looked at AF. A meta-analysis published in Circulation in 2021 showed a dose-response relationship. In trials testing > 1 g/d of marine omega-3 fatty acids, there was close to a 50% overall increase in risk for AF. In studies testing lower doses, there was a very modest 12% increase and a significant dose-response gradient.

For the relationship between omega-3 supplements and major cardiovascular events, at least 15 individual randomized trials have been conducted. There actually have been more meta-analyses of these randomized trials than individual trials. The meta-analyses tend to show a significant reduction of coronary events with omega-3 supplementation, but no reduction in stroke. This is true in both primary and secondary prevention trials.

The one exception to this finding is the REDUCE-IT trial testing high-dose eicosapentaenoic acid (EPA) (4 g/day of icosapent ethyl), and there was a 25%-30% reduction in both cardiovascular events and stroke. But there has been some criticism of the mineral oil placebo used in the REDUCE-IT trial that it may have had adverse effects on biomarkers and might have interfered with the absorption of statins in the placebo group. So, it will be important to have a replication trial of the high-dose EPA, findings in a trial using an inert placebo such as corn oil.

What should be done in the meantime? It’s important to think about prescription omega-3s vs over-the-counter fish oil. The US Food and Drug Administration (FDA) has approved prescription omega-3 medications for several indications, including severely elevated triglyceride levels (> 500 mg/dL). In the REDUCE-IT trial, those who had moderate elevations of triglycerides (≥ 150 mg/dL) or prevalent CVD or diabetes, plus two additional risk factors, were also considered to have indications based on the FDA labeling for icosapent ethyl.

What about patients who don’t meet these criteria for prescription omega-3s? In the VITAL trial (the large-scale primary prevention trial), there was a similar reduction in coronary events but no effect on stroke. Those who seemed to benefit the most in terms of at least 40% reduction in coronary events were participants who had low fish consumption at baseline, had two or more risk factors for cardiovascular disease, or were African American. 

Someone who rarely or never eats fish and has multiple risk factors for CVD, but doesn’t meet criteria for prescription omega-3 medication, may want to discuss with their clinician the use of over-the-counter fish oil supplements. But fish oil and other dietary supplements will never be a substitute for healthy diet and healthy lifestyle. There is a national recommendation for one to two servings of fish per week. For those planning to take fish oil, it’s important to use reputable sources of the supplement, and check the bottle for a quality control seal. It’s also really important to avoid megadoses of fish oil, because high doses have been linked to an increased risk for AF and bleeding.

Dr. Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston, disclosed ties with Mars Symbioscience for the COSMOS trial.

A version of this article appeared on Medscape.com.

I’d like to talk with you about a recent report in the British Medical Journal on the regular use of omega-3 fish oil supplements and the course of cardiovascular disease (CVD).

This is an observational study from the large-scale UK Biobank. The authors divided the participants into those with and those without CVD. In participants without CVD at baseline, those using fish oil supplements regularly had an increased incidence of both atrial fibrillation (AF) and stroke, whereas those with prevalent CVD had a reduction in the progression to major adverse cardiovascular events, which offset any increase in the risk for AF.

Observational studies of omega-3 supplements have potential limitations and confounding, and correlation in these studies does not prove causation. What do the randomized clinical trials of omega-3 supplements show? At least seven randomized trials have looked at AF. A meta-analysis published in Circulation in 2021 showed a dose-response relationship. In trials testing > 1 g/d of marine omega-3 fatty acids, there was close to a 50% overall increase in risk for AF. In studies testing lower doses, there was a very modest 12% increase and a significant dose-response gradient.

For the relationship between omega-3 supplements and major cardiovascular events, at least 15 individual randomized trials have been conducted. There actually have been more meta-analyses of these randomized trials than individual trials. The meta-analyses tend to show a significant reduction of coronary events with omega-3 supplementation, but no reduction in stroke. This is true in both primary and secondary prevention trials.

The one exception to this finding is the REDUCE-IT trial testing high-dose eicosapentaenoic acid (EPA) (4 g/day of icosapent ethyl), and there was a 25%-30% reduction in both cardiovascular events and stroke. But there has been some criticism of the mineral oil placebo used in the REDUCE-IT trial that it may have had adverse effects on biomarkers and might have interfered with the absorption of statins in the placebo group. So, it will be important to have a replication trial of the high-dose EPA, findings in a trial using an inert placebo such as corn oil.

What should be done in the meantime? It’s important to think about prescription omega-3s vs over-the-counter fish oil. The US Food and Drug Administration (FDA) has approved prescription omega-3 medications for several indications, including severely elevated triglyceride levels (> 500 mg/dL). In the REDUCE-IT trial, those who had moderate elevations of triglycerides (≥ 150 mg/dL) or prevalent CVD or diabetes, plus two additional risk factors, were also considered to have indications based on the FDA labeling for icosapent ethyl.

What about patients who don’t meet these criteria for prescription omega-3s? In the VITAL trial (the large-scale primary prevention trial), there was a similar reduction in coronary events but no effect on stroke. Those who seemed to benefit the most in terms of at least 40% reduction in coronary events were participants who had low fish consumption at baseline, had two or more risk factors for cardiovascular disease, or were African American. 

Someone who rarely or never eats fish and has multiple risk factors for CVD, but doesn’t meet criteria for prescription omega-3 medication, may want to discuss with their clinician the use of over-the-counter fish oil supplements. But fish oil and other dietary supplements will never be a substitute for healthy diet and healthy lifestyle. There is a national recommendation for one to two servings of fish per week. For those planning to take fish oil, it’s important to use reputable sources of the supplement, and check the bottle for a quality control seal. It’s also really important to avoid megadoses of fish oil, because high doses have been linked to an increased risk for AF and bleeding.

Dr. Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston, disclosed ties with Mars Symbioscience for the COSMOS trial.

A version of this article appeared on Medscape.com.

I’d like to talk with you about a recent report in the British Medical Journal on the regular use of omega-3 fish oil supplements and the course of cardiovascular disease (CVD).

This is an observational study from the large-scale UK Biobank. The authors divided the participants into those with and those without CVD. In participants without CVD at baseline, those using fish oil supplements regularly had an increased incidence of both atrial fibrillation (AF) and stroke, whereas those with prevalent CVD had a reduction in the progression to major adverse cardiovascular events, which offset any increase in the risk for AF.

Observational studies of omega-3 supplements have potential limitations and confounding, and correlation in these studies does not prove causation. What do the randomized clinical trials of omega-3 supplements show? At least seven randomized trials have looked at AF. A meta-analysis published in Circulation in 2021 showed a dose-response relationship. In trials testing > 1 g/d of marine omega-3 fatty acids, there was close to a 50% overall increase in risk for AF. In studies testing lower doses, there was a very modest 12% increase and a significant dose-response gradient.

For the relationship between omega-3 supplements and major cardiovascular events, at least 15 individual randomized trials have been conducted. There actually have been more meta-analyses of these randomized trials than individual trials. The meta-analyses tend to show a significant reduction of coronary events with omega-3 supplementation, but no reduction in stroke. This is true in both primary and secondary prevention trials.

The one exception to this finding is the REDUCE-IT trial testing high-dose eicosapentaenoic acid (EPA) (4 g/day of icosapent ethyl), and there was a 25%-30% reduction in both cardiovascular events and stroke. But there has been some criticism of the mineral oil placebo used in the REDUCE-IT trial that it may have had adverse effects on biomarkers and might have interfered with the absorption of statins in the placebo group. So, it will be important to have a replication trial of the high-dose EPA, findings in a trial using an inert placebo such as corn oil.

What should be done in the meantime? It’s important to think about prescription omega-3s vs over-the-counter fish oil. The US Food and Drug Administration (FDA) has approved prescription omega-3 medications for several indications, including severely elevated triglyceride levels (> 500 mg/dL). In the REDUCE-IT trial, those who had moderate elevations of triglycerides (≥ 150 mg/dL) or prevalent CVD or diabetes, plus two additional risk factors, were also considered to have indications based on the FDA labeling for icosapent ethyl.

What about patients who don’t meet these criteria for prescription omega-3s? In the VITAL trial (the large-scale primary prevention trial), there was a similar reduction in coronary events but no effect on stroke. Those who seemed to benefit the most in terms of at least 40% reduction in coronary events were participants who had low fish consumption at baseline, had two or more risk factors for cardiovascular disease, or were African American. 

Someone who rarely or never eats fish and has multiple risk factors for CVD, but doesn’t meet criteria for prescription omega-3 medication, may want to discuss with their clinician the use of over-the-counter fish oil supplements. But fish oil and other dietary supplements will never be a substitute for healthy diet and healthy lifestyle. There is a national recommendation for one to two servings of fish per week. For those planning to take fish oil, it’s important to use reputable sources of the supplement, and check the bottle for a quality control seal. It’s also really important to avoid megadoses of fish oil, because high doses have been linked to an increased risk for AF and bleeding.

Dr. Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston, disclosed ties with Mars Symbioscience for the COSMOS trial.

A version of this article 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.

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.

Over a period of 5 years, the likelihood of major adverse cardiovascular events (MACE) in patients with psoriasis and dyslipidemia who were on statin therapy was 40% greater than that in non-psoriasis patients with dyslipidemia on statin therapy, even after adjusting for covariates, results from a large retrospective study showed.

“It is well-established that psoriasis is an independent risk factor for the development of MACE, with cardiometabolic risk factors being more prevalent and incident among patients with psoriasis,” the study’s first author Ana Ormaza Vera, MD, a dermatology research fellow at Eastern Virginia Medical School, Norfolk, said in an interview after the annual meeting of the Society for Investigational Dermatology, where the study was presented during a late-breaking abstract session.

Dr. Ormaza Vera

Current guidelines from the joint American Academy of Dermatology/National Psoriasis Foundation and the American Academy of Cardiology/American Heart Association Task Force recommend statins, a lipid-lowering and anti-inflammatory therapy, “for patients with psoriasis who have additional risk-enhancing factors, similar to recommendations made for the general population without psoriasis,” she noted. But how the incidence of MACE differs between patients with and without psoriasis while on statin therapy “has not been explored in real-world settings,” she added.

To address this question, the researchers used real-world data from the TriNetX health research network to identify individuals aged 18-90 years with a diagnosis of both psoriasis and lipid disorders who were undergoing treatment with statins. Those with a prior history of MACE were excluded from the analysis. Patients with lipid disorders on statin therapy, but without psoriatic disease, were matched 1:1 by age, sex, race, ethnicity, common risk factors for MACE, and medications shown to reduce MACE risk. The researchers then assessed the cohorts 5 years following their first statin prescription and used the TriNetX analytics tool to calculate the odds ratio (OR) with 95% CI to evaluate the likelihood of MACE in the presence of statin therapy.

Dr. Ormaza Vera and colleagues identified 20,660 patients with psoriasis and 2,768,429 patients without psoriasis who met the criteria for analysis. After propensity score matching, each cohort included 20,660 patients with a mean age of 60 years. During the 5-year observation period, 2725 patients in the psoriasis cohort experienced MACE compared with 2203 patients in the non-psoriasis cohort (OR, 1.40; 95% CI, 1.317-1.488).

“This was an unexpected outcome that challenges the current understanding and highlights the need for further research into tailored treatments for cardiovascular risk in psoriasis patients,” Dr. Ormaza Vera told this news organization.

She acknowledged certain limitations of the study, including its retrospective design, the inherent limitations of an observational study, and the use of electronic medical record data.

Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, who was asked to comment on the study results, said that the findings imply that there is more than statin use alone to protect someone with psoriasis from having an increased risk for MACE. “This is not really surprising because statin use alone is only part of a prevention strategy in someone with psoriasis who usually has multiple comorbidities,” Dr. Green said. “On the other hand, the study only went out for 5 years and cardiovascular disease is a long accumulating process, so it could also be too early to demonstrate MACE prevention.”

The study was funded by a grant from the American Skin Association. Dr. Ormaza Vera and her coauthors reported having no relevant disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

A version of this article appeared on Medscape.com .

Over a period of 5 years, the likelihood of major adverse cardiovascular events (MACE) in patients with psoriasis and dyslipidemia who were on statin therapy was 40% greater than that in non-psoriasis patients with dyslipidemia on statin therapy, even after adjusting for covariates, results from a large retrospective study showed.

“It is well-established that psoriasis is an independent risk factor for the development of MACE, with cardiometabolic risk factors being more prevalent and incident among patients with psoriasis,” the study’s first author Ana Ormaza Vera, MD, a dermatology research fellow at Eastern Virginia Medical School, Norfolk, said in an interview after the annual meeting of the Society for Investigational Dermatology, where the study was presented during a late-breaking abstract session.

Dr. Ormaza Vera

Current guidelines from the joint American Academy of Dermatology/National Psoriasis Foundation and the American Academy of Cardiology/American Heart Association Task Force recommend statins, a lipid-lowering and anti-inflammatory therapy, “for patients with psoriasis who have additional risk-enhancing factors, similar to recommendations made for the general population without psoriasis,” she noted. But how the incidence of MACE differs between patients with and without psoriasis while on statin therapy “has not been explored in real-world settings,” she added.

To address this question, the researchers used real-world data from the TriNetX health research network to identify individuals aged 18-90 years with a diagnosis of both psoriasis and lipid disorders who were undergoing treatment with statins. Those with a prior history of MACE were excluded from the analysis. Patients with lipid disorders on statin therapy, but without psoriatic disease, were matched 1:1 by age, sex, race, ethnicity, common risk factors for MACE, and medications shown to reduce MACE risk. The researchers then assessed the cohorts 5 years following their first statin prescription and used the TriNetX analytics tool to calculate the odds ratio (OR) with 95% CI to evaluate the likelihood of MACE in the presence of statin therapy.

Dr. Ormaza Vera and colleagues identified 20,660 patients with psoriasis and 2,768,429 patients without psoriasis who met the criteria for analysis. After propensity score matching, each cohort included 20,660 patients with a mean age of 60 years. During the 5-year observation period, 2725 patients in the psoriasis cohort experienced MACE compared with 2203 patients in the non-psoriasis cohort (OR, 1.40; 95% CI, 1.317-1.488).

“This was an unexpected outcome that challenges the current understanding and highlights the need for further research into tailored treatments for cardiovascular risk in psoriasis patients,” Dr. Ormaza Vera told this news organization.

She acknowledged certain limitations of the study, including its retrospective design, the inherent limitations of an observational study, and the use of electronic medical record data.

Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, who was asked to comment on the study results, said that the findings imply that there is more than statin use alone to protect someone with psoriasis from having an increased risk for MACE. “This is not really surprising because statin use alone is only part of a prevention strategy in someone with psoriasis who usually has multiple comorbidities,” Dr. Green said. “On the other hand, the study only went out for 5 years and cardiovascular disease is a long accumulating process, so it could also be too early to demonstrate MACE prevention.”

The study was funded by a grant from the American Skin Association. Dr. Ormaza Vera and her coauthors reported having no relevant disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

A version of this article appeared on Medscape.com .

Over a period of 5 years, the likelihood of major adverse cardiovascular events (MACE) in patients with psoriasis and dyslipidemia who were on statin therapy was 40% greater than that in non-psoriasis patients with dyslipidemia on statin therapy, even after adjusting for covariates, results from a large retrospective study showed.

“It is well-established that psoriasis is an independent risk factor for the development of MACE, with cardiometabolic risk factors being more prevalent and incident among patients with psoriasis,” the study’s first author Ana Ormaza Vera, MD, a dermatology research fellow at Eastern Virginia Medical School, Norfolk, said in an interview after the annual meeting of the Society for Investigational Dermatology, where the study was presented during a late-breaking abstract session.

Dr. Ormaza Vera

Current guidelines from the joint American Academy of Dermatology/National Psoriasis Foundation and the American Academy of Cardiology/American Heart Association Task Force recommend statins, a lipid-lowering and anti-inflammatory therapy, “for patients with psoriasis who have additional risk-enhancing factors, similar to recommendations made for the general population without psoriasis,” she noted. But how the incidence of MACE differs between patients with and without psoriasis while on statin therapy “has not been explored in real-world settings,” she added.

To address this question, the researchers used real-world data from the TriNetX health research network to identify individuals aged 18-90 years with a diagnosis of both psoriasis and lipid disorders who were undergoing treatment with statins. Those with a prior history of MACE were excluded from the analysis. Patients with lipid disorders on statin therapy, but without psoriatic disease, were matched 1:1 by age, sex, race, ethnicity, common risk factors for MACE, and medications shown to reduce MACE risk. The researchers then assessed the cohorts 5 years following their first statin prescription and used the TriNetX analytics tool to calculate the odds ratio (OR) with 95% CI to evaluate the likelihood of MACE in the presence of statin therapy.

Dr. Ormaza Vera and colleagues identified 20,660 patients with psoriasis and 2,768,429 patients without psoriasis who met the criteria for analysis. After propensity score matching, each cohort included 20,660 patients with a mean age of 60 years. During the 5-year observation period, 2725 patients in the psoriasis cohort experienced MACE compared with 2203 patients in the non-psoriasis cohort (OR, 1.40; 95% CI, 1.317-1.488).

“This was an unexpected outcome that challenges the current understanding and highlights the need for further research into tailored treatments for cardiovascular risk in psoriasis patients,” Dr. Ormaza Vera told this news organization.

She acknowledged certain limitations of the study, including its retrospective design, the inherent limitations of an observational study, and the use of electronic medical record data.

Lawrence J. Green, MD, clinical professor of dermatology, George Washington University, Washington, who was asked to comment on the study results, said that the findings imply that there is more than statin use alone to protect someone with psoriasis from having an increased risk for MACE. “This is not really surprising because statin use alone is only part of a prevention strategy in someone with psoriasis who usually has multiple comorbidities,” Dr. Green said. “On the other hand, the study only went out for 5 years and cardiovascular disease is a long accumulating process, so it could also be too early to demonstrate MACE prevention.”

The study was funded by a grant from the American Skin Association. Dr. Ormaza Vera and her coauthors reported having no relevant disclosures. Dr. Green disclosed that he is a speaker, consultant, or investigator for many pharmaceutical companies.

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.

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.

Women who used levonorgestrel-releasing intrauterine devices (LG-IUDs) were 22% less likely to have a stroke than those who did not use hormonal contraception, new research suggested.

The Danish study, which included 1.7 million women, also showed no increased risk for intracerebral hemorrhage for those using the IUDs.

“The finding raises the question of whether levonorgestrel, in addition to its contraceptive properties, could have the potential to prevent (ischemic stroke),” wrote corresponding author Tom Skyhøj Olsen, MD, PhD, of Bispebjerg University Hospital, Copenhagen, Denmark, and coauthors.

The research was published online on May 16, 2024, in the journal Stroke.
 

A Big-Picture Look

Commonly used combined hormonal contraceptives that contain both progestins and ethinylestradiol are linked to an increased risk for ischemic stroke. Previous research suggested that progestin-only options, including LG-IUDs, are not associated with elevated risk and may even lower the risk. The IUDs had also been previously associated with lower risk for thromboembolism.

The new study was a large-scale investigation of all reproductive-age women in Denmark that compared stroke risk in those who used the progestin-only IUDs with those who didn’t use hormonal contraception. It also examined the risk for intracerebral hemorrhage, which had not been previously studied.

The historic cohort study drew on several large national databases in Denmark, including the Danish Stroke Registry, to evaluate the interplay between IUD contraception, stroke, and intracerebral hemorrhage. The study looked back at data collected on all nonpregnant Danish women aged 18-49 years who lived in Denmark for some or all of the period between 2004 and 2021.

Mean age of the 1.7 million women in the study was 30 years, and the mean follow-up period was about 7 years. More than 364,700 participants used LG-IUDs.

During the study period, 2916 women had an ischemic stroke, and 367 experienced intracerebral hemorrhage.

Among IUD users, the incidence of stroke was 19.2 per 100,000 person years. For women who didn’t use contraception, the rate was 25.2.

Overall, those who used an IUD had a 22% lower risk for ischemic stroke than those who didn’t (incidence rate ratio [IRR], 0.78; 95% CI, 0.70-0.88).

The incidence of brain bleeds was similar in both groups.

Does Age Matter?

The incidence of stroke did not differ significantly between the three age groups analyzed in the study: Women aged 18-29 years, 30-39 years, and 40-49 years. Incidence rates of intracerebral hemorrhage were similar between age groups 30-39 years and 40-49 years, but the risk was higher for those aged 18-29 years than for those aged 40-49 years (IRR, 4.49; 95% CI, 1.65-12.19).

The researchers urged caution in interpreting the apparent higher risk for brain bleeds in younger women, noting that the overall number of events was low, resulting in wide CIs.

Investigators also found that women who moved to Denmark from non-Western countries had a significantly lower stroke rate than native Danes. Incidence rates of intracerebral hemorrhage were not affected by country of origin.

The research team noted that they had only indirect information about women’s stroke risk factors including diabetes, high blood pressure, and migraine and had no information about smoking, alcohol consumption, and body mass index.

“Regarding a possible potential for stroke prevention, our study cannot stand alone and requires confirmation in further research. Even though the incidence rate for [ischemic stroke] and [intracerebral hemorrhage] did not significantly change after adjustment for various factors, bias…cannot be fully ruled out,” the researchers wrote.

The study was funded by the Aase og Ejnar Danielsens Fond and Familien Hede Nielsens Fond. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women who used levonorgestrel-releasing intrauterine devices (LG-IUDs) were 22% less likely to have a stroke than those who did not use hormonal contraception, new research suggested.

The Danish study, which included 1.7 million women, also showed no increased risk for intracerebral hemorrhage for those using the IUDs.

“The finding raises the question of whether levonorgestrel, in addition to its contraceptive properties, could have the potential to prevent (ischemic stroke),” wrote corresponding author Tom Skyhøj Olsen, MD, PhD, of Bispebjerg University Hospital, Copenhagen, Denmark, and coauthors.

The research was published online on May 16, 2024, in the journal Stroke.
 

A Big-Picture Look

Commonly used combined hormonal contraceptives that contain both progestins and ethinylestradiol are linked to an increased risk for ischemic stroke. Previous research suggested that progestin-only options, including LG-IUDs, are not associated with elevated risk and may even lower the risk. The IUDs had also been previously associated with lower risk for thromboembolism.

The new study was a large-scale investigation of all reproductive-age women in Denmark that compared stroke risk in those who used the progestin-only IUDs with those who didn’t use hormonal contraception. It also examined the risk for intracerebral hemorrhage, which had not been previously studied.

The historic cohort study drew on several large national databases in Denmark, including the Danish Stroke Registry, to evaluate the interplay between IUD contraception, stroke, and intracerebral hemorrhage. The study looked back at data collected on all nonpregnant Danish women aged 18-49 years who lived in Denmark for some or all of the period between 2004 and 2021.

Mean age of the 1.7 million women in the study was 30 years, and the mean follow-up period was about 7 years. More than 364,700 participants used LG-IUDs.

During the study period, 2916 women had an ischemic stroke, and 367 experienced intracerebral hemorrhage.

Among IUD users, the incidence of stroke was 19.2 per 100,000 person years. For women who didn’t use contraception, the rate was 25.2.

Overall, those who used an IUD had a 22% lower risk for ischemic stroke than those who didn’t (incidence rate ratio [IRR], 0.78; 95% CI, 0.70-0.88).

The incidence of brain bleeds was similar in both groups.

Does Age Matter?

The incidence of stroke did not differ significantly between the three age groups analyzed in the study: Women aged 18-29 years, 30-39 years, and 40-49 years. Incidence rates of intracerebral hemorrhage were similar between age groups 30-39 years and 40-49 years, but the risk was higher for those aged 18-29 years than for those aged 40-49 years (IRR, 4.49; 95% CI, 1.65-12.19).

The researchers urged caution in interpreting the apparent higher risk for brain bleeds in younger women, noting that the overall number of events was low, resulting in wide CIs.

Investigators also found that women who moved to Denmark from non-Western countries had a significantly lower stroke rate than native Danes. Incidence rates of intracerebral hemorrhage were not affected by country of origin.

The research team noted that they had only indirect information about women’s stroke risk factors including diabetes, high blood pressure, and migraine and had no information about smoking, alcohol consumption, and body mass index.

“Regarding a possible potential for stroke prevention, our study cannot stand alone and requires confirmation in further research. Even though the incidence rate for [ischemic stroke] and [intracerebral hemorrhage] did not significantly change after adjustment for various factors, bias…cannot be fully ruled out,” the researchers wrote.

The study was funded by the Aase og Ejnar Danielsens Fond and Familien Hede Nielsens Fond. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women who used levonorgestrel-releasing intrauterine devices (LG-IUDs) were 22% less likely to have a stroke than those who did not use hormonal contraception, new research suggested.

The Danish study, which included 1.7 million women, also showed no increased risk for intracerebral hemorrhage for those using the IUDs.

“The finding raises the question of whether levonorgestrel, in addition to its contraceptive properties, could have the potential to prevent (ischemic stroke),” wrote corresponding author Tom Skyhøj Olsen, MD, PhD, of Bispebjerg University Hospital, Copenhagen, Denmark, and coauthors.

The research was published online on May 16, 2024, in the journal Stroke.
 

A Big-Picture Look

Commonly used combined hormonal contraceptives that contain both progestins and ethinylestradiol are linked to an increased risk for ischemic stroke. Previous research suggested that progestin-only options, including LG-IUDs, are not associated with elevated risk and may even lower the risk. The IUDs had also been previously associated with lower risk for thromboembolism.

The new study was a large-scale investigation of all reproductive-age women in Denmark that compared stroke risk in those who used the progestin-only IUDs with those who didn’t use hormonal contraception. It also examined the risk for intracerebral hemorrhage, which had not been previously studied.

The historic cohort study drew on several large national databases in Denmark, including the Danish Stroke Registry, to evaluate the interplay between IUD contraception, stroke, and intracerebral hemorrhage. The study looked back at data collected on all nonpregnant Danish women aged 18-49 years who lived in Denmark for some or all of the period between 2004 and 2021.

Mean age of the 1.7 million women in the study was 30 years, and the mean follow-up period was about 7 years. More than 364,700 participants used LG-IUDs.

During the study period, 2916 women had an ischemic stroke, and 367 experienced intracerebral hemorrhage.

Among IUD users, the incidence of stroke was 19.2 per 100,000 person years. For women who didn’t use contraception, the rate was 25.2.

Overall, those who used an IUD had a 22% lower risk for ischemic stroke than those who didn’t (incidence rate ratio [IRR], 0.78; 95% CI, 0.70-0.88).

The incidence of brain bleeds was similar in both groups.

Does Age Matter?

The incidence of stroke did not differ significantly between the three age groups analyzed in the study: Women aged 18-29 years, 30-39 years, and 40-49 years. Incidence rates of intracerebral hemorrhage were similar between age groups 30-39 years and 40-49 years, but the risk was higher for those aged 18-29 years than for those aged 40-49 years (IRR, 4.49; 95% CI, 1.65-12.19).

The researchers urged caution in interpreting the apparent higher risk for brain bleeds in younger women, noting that the overall number of events was low, resulting in wide CIs.

Investigators also found that women who moved to Denmark from non-Western countries had a significantly lower stroke rate than native Danes. Incidence rates of intracerebral hemorrhage were not affected by country of origin.

The research team noted that they had only indirect information about women’s stroke risk factors including diabetes, high blood pressure, and migraine and had no information about smoking, alcohol consumption, and body mass index.

“Regarding a possible potential for stroke prevention, our study cannot stand alone and requires confirmation in further research. Even though the incidence rate for [ischemic stroke] and [intracerebral hemorrhage] did not significantly change after adjustment for various factors, bias…cannot be fully ruled out,” the researchers wrote.

The study was funded by the Aase og Ejnar Danielsens Fond and Familien Hede Nielsens Fond. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.

There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.

Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).

“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).

Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes. 

The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.

The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.

Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
 

Lp(a) and Chronic Kidney Disease

When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.

Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.

Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.

The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.

The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.

A version of this article appeared on Medscape.com.

LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.

There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.

Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).

“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).

Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes. 

The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.

The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.

Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
 

Lp(a) and Chronic Kidney Disease

When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.

Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.

Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.

The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.

The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.

A version of this article appeared on Medscape.com.

LYON, FRANCE — High levels of lipoprotein(a) [Lp(a)] in the blood are associated with a significantly increased risk for chronic kidney disease, report investigators who are studying the link in a two-part study of more than 100,000 people.

There is already genetic evidence showing that Lp(a) can cause cardiovascular conditions, including myocardial infarction, aortic valve stenosis, peripheral artery disease, and ischemic stroke.

Now, researchers presenting at the European Atherosclerosis Society (EAS) 2024 Congress are adding new organs – the kidneys – to the list of those that can be damaged by elevated Lp(a).

“This is very important,” said lead investigator Anne Langsted, MD, PhD, DMSc, from the Department of Clinical Biochemistry at the Rigshospitalet in Denmark. And “hopefully, we’ll have a treatment for Lp(a) on the market very soon. Until then, I think individuals who have kidney disease would benefit a lot from reducing other risk factors, if they also have high levels” of Lp(a).

Using data gathered from the Copenhagen General Population Study, the study involved 108,439 individuals who had a range of tests including estimated glomerular filtration rate (eGFR), plasma Lp(a) levels, and LPA genotyping. The patients were then linked to a series of national registries to study outcomes. 

The researchers conducted two separate analyses: an observational study of Lp(a) levels in 70,040 individuals and a Mendelian randomization study of LPA kringle IV–type 2 domain repeats in 106,624 individuals. The number of those repeats is inversely associated with median Lp(a) plasma levels.

The observational study showed that eGFR decreased with increasing median plasma Lp(a) levels; the Mendelian randomization study indicated that eGFR decreased KIV-2 repeat numbers dropped.

Across both parts of the study, it was found that each 50 mg/dL increase in plasma Lp(a) levels was associated with an increased risk of at least 25% for chronic kidney disease.
 

Lp(a) and Chronic Kidney Disease

When high plasma levels of Lp(a) have been spotted before in patients with kidney disease, “we’ve kind of assumed that it was probably the kidney disease that caused the higher levels,” Dr. Langsted said. But her team hypothesized that the opposite was at play and that Lp(a) levels are genetically determined, and increased plasma Lp(a) levels may be causally associated with rising risk for chronic kidney disease.

Gerald F. Watts, MD, PhD, DSc, Winthrop Professor of cardiometabolic and internal medicine at the University of Western Australia in Perth, and co-chair of the study, said in an interview that “although Mendelian randomization is a technique that allows you to infer causality, it’s probably a little bit more complex than that in reality,” adding that there is likely a bidirectional relationship between Lp(a) and chronic kidney disease.

Having increased Lp(a) levels on their own is not sufficient to trigger chronic kidney disease. “You probably need another event and then you get into a vicious cycle,” Dr. Watts said.

The mechanism linking Lp(a) with chronic kidney disease remains unclear, but Dr. Watts explained that the lipoprotein probably damages the renal tubes when it is reabsorbed after it dissociates from low-density lipoprotein cholesterol.

The next step will be to identify the people who are most susceptible to this and figure out what treatment might help. Dr. Watts suggested that gene silencing, in which Lp(a) is “completely obliterated,” will lead to an improvement in renal function.

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

BASEL, SWITZERLAND — The anti-inflammatory agent colchicine failed to show significant benefit in the treatment of patients with non-cardioembolic ischemic stroke in the primary analysis of the CONVINCE trial. However, the results did reveal a significant reduction in recurrent stroke and cardiovascular events in the per-protocol analysis and in the subgroup of patients with coronary artery disease.

“Although the primary endpoint was neutral, the CONVINCE results support the hypothesis that long-term anti-inflammatory therapy with colchicine may reduce recurrent stroke and cardiovascular events, specifically in stroke patients with atherosclerosis,” lead investigator Peter Kelly, MD, University College Dublin School of Medicine, Dublin, Ireland, concluded.

The results were presented at the European Stroke Organization Conference (ESOC) 2024.

Inflammation, Dr. Kelly said, plays an important role in the pathophysiology of atherosclerotic plaque, a major cause of cardiovascular events and ischemic strokes.

Colchicine, an established, widely available, low-cost drug that reduces inflammatory response, has been shown to reduce recurrent vascular events in patients with coronary artery disease.

The CONVINCE trial was conducted to see whether colchicine could show similar benefits in patients with non-severe, non-cardioembolic stroke or transient ischemic attack.

Conducted in 16 European countries and Canada, the CONVINCE trial included 3154 patients with a recent non-cardioembolic nondisabling ischemic stroke or high-risk transient ischemic attack. They were randomly assigned to receive colchicine (0.5 mg/d) or placebo.

Key exclusion criteria included evidence of atrial fibrillation or other source of cardioembolism, a defined cause of stroke other than atherosclerosis or small vessel disease, a glomerular filtration rate below 50 mL/min, and the use of drugs that interact with colchicine.

The primary endpoint was a composite of first recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Study participants were followed-up over 36 months.

Results of the primary intention-to-treat analysis showed that the primary endpoint occurred in 153 patients randomized to low-dose colchicine (9.8%) versus 185 in the placebo group (11.8%). This translated into a hazard ratio (HR) of 0.84 (95% CI, 0.68-1.05; P = .12) — a nonsignificant result.

Reduced levels of C-reactive protein in the colchicine group showed the anti-inflammatory effect of treatment with colchicine, Dr. Kelly reported.

In a prespecified on-treatment analysis (excluding patients with major protocol violations), colchicine did show a significant benefit in the primary endpoint (HR, 0.80; 95% CI, 0.63-0.99).
 

A Novel Target for Stroke Treatment

In addition, significantly reduced rates of recurrent stroke or cardiovascular events were observed in the subgroup of patients with a history of coronary artery disease.

In an updated meta-analysis of existing colchicine studies including CONVINCE, there was a significant reduction in the risk for ischemic stroke (risk ratio, 0.73; 95% CI, 0.58-0.90).

“The signals of benefit of colchicine in secondary analyses are in line with findings from previous trials and indicate the potential of colchicine in prevention after stroke,” Dr. Kelly said.

He pointed out that the COVID pandemic reduced the planned follow-up time in the CONVINCE trial, which led to the study being underpowered for the primary analysis.

“Further trials are needed in all stroke subtypes, but with particular focus on patients with objective evidence of atherosclerosis,” he said.

Commenting on the findings, Mira Katan, MD, University Hospital of Basel, Switzerland, noted that inflammation represents a novel target for stroke treatment.

“We have never before looked at treating inflammation in stroke. Although the primary endpoint was not reached in the CONVINCE study, the on-treatment analysis and meta-analysis showed a risk reduction, and we know colchicine works in cardiology. I think this is a fantastic trial, giving us a new target for stroke therapy,” Dr. Katan said.

“I think we have a new tool, but of course we need further trials to confirm that,” she added.

The CONVINCE trial was supported by Health Research Board Ireland, Deutsche Forschungsgesellschaft, Fonds Wetenschappelijk Onderzoek (FWO), and the Irish Heart Foundation. Dr. Kelly received funding from the Irish Heart Foundation. Dr. Katan reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from 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 appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from 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 appeared on Medscape.com.

Exercise recommendations typically focus on the duration of physical activity. For example, the World Health Organization advises at least 150 minutes of moderate physical activity per week. A new analysis of data from the Women’s Health Study, published in JAMA Internal Medicine, suggested that step count could also be a useful metric. For some, such a recommendation might be easier to follow.

“It’s not so easy to keep track of how long you’ve been moderately active in a given week,” Cary P. Gross, MD, from the Department of Medicine at Yale University in New Haven, Connecticut, wrote in an editorial. “Counting steps might be easier for some people, especially since most carry a phone that can serve as a pedometer.”
 

The 10,000-Step Recommendation

However, there are no well-founded recommendations for step counts, partly due to a lack of scientific evidence linking steps with mortality and cardiovascular diseases. The often-cited 10,000 steps per day originated from a marketing campaign in Japan in the 1960s.

The research team led by Rikuta Hamaya, MD, from the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, analyzed data from participants in the Women’s Health Study. This clinical trial in the United States from 1992 to 2004 investigated the use of aspirin and vitamin E for cancer and cardiovascular disease prevention.

The current analysis included 14,399 women who were aged ≥ 62 years and had not developed cardiovascular disease or cancer. Between 2011 and 2015, they measured their physical activity and step count over 7 days using an accelerometer. They were followed-up for an average of 9 years.
 

Risk Reduction With Both Parameters

Moderate physical activity among the participants amounted to a median of 62 minutes per week, with a median daily step count of 5183. Hamaya and his colleagues found that both physical activity parameters were associated with lower mortality and reduced risk for cardiovascular diseases.

Participants who engaged in more than the recommended 150 minutes of moderate-intensity activity per week had a 32% lower mortality risk than those who were the least physically active. Women with > 7000 steps per day had a 42% lower mortality risk than those with the lowest daily step count.

Women in the top three quartiles of physical activity outlived those in the lowest quartile by an average of 2.22 months (time) or 2.36 months (steps), according to Hamaya and his team. The survival advantage was independent of body mass index.

For the endpoint of cardiovascular diseases (heart attack, stroke, and cardiovascular mortality), the researchers observed similar results as for mortality.
 

More Ways to Reach the Goal

Dr. Hamaya emphasized the importance of offering multiple ways to meet exercise recommendations: “For some, especially younger people, physical activity includes sports like tennis, soccer, walking, or jogging. All these can be tracked well with step counting. But for others, activity means cycling or swimming, which is easier to measure by duration.”

For Dr. Gross, the new findings provide a basis for using step counts to set physical activity goals — both in individual patient counseling and in formal guidelines. However, he stressed that further studies are necessary.

“The results need to be replicated in various populations, not just among men and younger people but also among ethnic minorities and lower-income populations, who often have less time and space for structured physical activity.”
 

This story was translated from 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 appeared on Medscape.com.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.