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Women with Autoimmune Liver Diseases Still Face Increased CVD Risks
WASHINGTON – , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.
“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.
“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”
Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.
Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.
The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.
The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.
Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).
Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).
There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).
When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).
Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.
“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”
Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.
As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.
“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”
Dr. Redfield and Dr. Kelson reported no relevant disclosures.
WASHINGTON – , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.
“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.
“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”
Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.
Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.
The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.
The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.
Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).
Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).
There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).
When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).
Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.
“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”
Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.
As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.
“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”
Dr. Redfield and Dr. Kelson reported no relevant disclosures.
WASHINGTON – , according to a study presented at the annual Digestive Disease Week® (DDW).
In particular, women with autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) appear to have higher risks than women without AIH or PBC. Those with primary sclerosing cholangitis (PSC) don’t seem to have increased risks.
“We know that cardiovascular disease remains the number one cause of death, but the mortality rate for women over the last decade has plateaued, whereas in men it’s actually declining due to interventions,” said lead author Rachel Redfield, MD, a transplant hepatology fellow at Thomas Jefferson University Hospital in Philadelphia.
“This is likely because we don’t have adequate risk stratification, especially for women,” she said. “We know that immune-mediated diseases — such as rheumatoid arthritis and psoriasis — carry a higher risk of cardiovascular disease, but there’s not a lot of data on our autoimmune liver disease patients.”
Although being a female can offer protection against some CVD risks, the atherosclerotic cardiovascular disease (ASCVD) 10-year risk score calculator recommended by the American College of Cardiology doesn’t include chronic inflammatory diseases associated with increased CVD risk, including AILD.
Dr. Redfield and colleagues conducted a multicenter, retrospective cohort study of patients with AIH, PBC, and PSC from 1999-2019. Using TriNetX data, the researchers looked at women with AILD who also had diabetes mellitus, hypertension, and hyperlipidemia, as well as a control group of men and women with these same disorders, excluding those who used biologics, immune modulators, and steroids or had other autoimmune disorders.
The research team used 1:1 propensity-score matching for women in the study group and in the control group based on age, race, ethnicity, ASCVD risk factors, and tobacco use. Women in the study group and men in the control group were matched for age, race, ethnicity, and tobacco use.
The primary outcome was summative cardiovascular risk, including unstable angina, acute myocardial infarction, presence of coronary angioplasty implant, coronary artery bypass, percutaneous coronary intervention, and cerebral infarction.
Overall, women with AIH had a significantly higher cardiovascular risk compared to women without AIH, at 25.4% versus 20.6% (P = .0007).
Specifically, women with PBC had a significantly higher cardiovascular risk compared to women without PBC, at 27.05% versus 20.9% (P < .0001).
There wasn’t a significant difference in risk between women with and without PSC, at 27.5% versus 21.8% (P = .27).
When compared to men without disease, women with AIH didn’t have a statistically significant higher risk, at 25.3% versus 24.2% (P = .44). Similarly, there didn’t appear to be a significant difference between women with PBC and men without PBC, at 26.9% versus 25.9% (P = .52), or between women with PSC and men without PSC, at 27.7% versus 26.2% (P = .78).
Dr. Redfield and colleagues then compared the ASCVD-calculated risk versus database risk, finding that in each group of women with AILD — including AIH, PBC, and PSC — the ASCVD-calculated risk was around 11%, compared with database risk scores of 25% for AIH, 27% for PBC, and 28% for PSC. These database risks appeared similar to both the ASCVD and database risk percentages for men.
“So potentially there’s an oversight in women with any kind of inflammatory disease, but specifically here, autoimmune liver diseases,” she said. “We really need to enhance our risk assessment strategies to take into account their risk and optimize patient outcomes.”
Dr. Redfield noted the limitations with using TriNetX data, including coding consistency among providers and healthcare organizations, unknown patient follow-up dates, and the inability to capture various inflammatory disease phenotypes, such as autoimmune hepatitis with multiple flares, which may be associated with higher cardiovascular risks.
As an attendee of the DDW session, Kenneth Kelson, MD, a gastroenterologist with Fremont Medical Group and Washington Hospital Healthcare System in Fremont, California, noted the importance of investigating the effects of different types of statins in these patients. Although the research team looked at top-level differences among statin users, finding that women with AILD were more likely to be on a statin, they didn’t incorporate statin therapy in the propensity-score matching model.
“Lipid-soluble statins are known to cause more liver trouble, even though it’s pretty low,” Dr. Kelson said. “Whereas the water-soluble statins have a lower incidence of liver issues.”
Dr. Redfield and Dr. Kelson reported no relevant disclosures.
FROM DDW 2024
The Tyranny of Beta-Blockers
Beta-blockers are excellent drugs. They’re cheap and effective; feature prominently in hypertension guidelines; and remain a sine qua non for coronary artery disease, myocardial infarction, and heart failure treatment. They’ve been around forever, and we know they work. Good luck finding an adult medicine patient who isn’t on one.
Beta-blockers act by slowing resting heart rate (and blunting the heart rate response to exercise. The latter is a pernicious cause of activity intolerance that often goes unchecked. Even when the adverse effects of beta-blockers are appreciated, providers are loath to alter dosing, much less stop the drug. After all, beta-blockers are an integral part of guideline-directed medical therapy (GDMT), and GDMT saves lives.
Balancing Heart Rate and Stroke Volume Effects
To augment cardiac output and optimize oxygen uptake (VO2) during exercise, we need the heart rate response. In fact, the heart rate response contributes more to cardiac output than augmenting stroke volume (SV) and more to VO2 than the increase in arteriovenous (AV) oxygen difference. An inability to increase the heart rate commensurate with physiologic work is called chronotropic incompetence (CI). That’s what beta-blockers do ─ they cause CI.
Physiology dictates that CI will cause activity intolerance. That said, it’s hard to quantify the impact from beta-blockers at the individual patient level. Data suggest the heart rate effect is profound. A study in patients without heart failure found that 22% of participants on beta-blockers had CI, and the investigators used a conservative CI definition (≤ 62% of heart rate reserve used). A recent report published in JAMA Cardiology found that stopping beta-blockers in patients with heart failure allowed for an extra 30 beats/min at max exercise.
Wasserman and Whipp’s textbook, the last word on all things exercise, presents a sample subject who undergoes two separate cardiopulmonary exercise tests (CPETs). Before the first, he’s given a placebo, and before the second, he gets an intravenous beta-blocker. He’s a 23-year-old otherwise healthy male — the perfect test case for isolating beta-blocker impact without confounding by comorbid diseases, other medications, or deconditioning. His max heart rate dropped by 30 beats/min after the beta-blocker, identical to what we saw in the JAMA Cardiology study (with the heart rate increasing by 30 beats/min following withdrawal). Case closed. Stop the beta-blockers on your patients so they can meet their exercise goals and get healthy!
Such pithy enthusiasm discounts physiology’s complexities. When blunting our patient’s heart rate response with beta-blockers, we also increase diastolic filling time, which increases SV. For the 23-year-old in Wasserman and Whipp’s physiology textbook, the beta-blocker increased O2 pulse (the product of SV and AV difference). Presumably, this is mediated by the increased SV. There was a net reduction in VO2 peak, but it was nominal, suggesting that the drop in heart rate was largely offset by the increase in O2 pulse. For the patients in the JAMA Cardiology study, the entire group had a small increase in VO2 peak with beta-blocker withdrawal, but the effect differed by left ventricular function. Across different studies, the beta-blocker effect on heart rate is consistent but the change in overall exercise capacity is not.
Patient Variability in Beta-Blocker Response
In addition to left ventricular function, there are other factors likely to drive variability at the patient level. We’ve treated the response to beta-blockers as a class effect — an obvious oversimplification. The impact on exercise and the heart will vary by dose and drug (eg, atenolol vs metoprolol vs carvedilol, and so on). Beta-blockers can also affect the lungs, and we’re still debating how cautious to be in the presence of asthma or chronic obstructive pulmonary disease.
In a world of infinite time, resources, and expertise, we’d CPET everyone before and after beta-blocker use. Our current reality requires the unthinkable: We’ll have to talk to each other and our patients. For example, heart failure guidelines recommend titrating drugs to match the dose from trials that proved efficacy. These doses are quite high. Simple discussion with the cardiologist and the patient may allow for an adjustment back down with careful monitoring and close attention to activity tolerance. With any luck, you’ll preserve the benefits from GDMT while optimizing your patient›s ability to meet their exercise goals.
Dr. Holley, professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center, Washington, disclosed ties with Metapharm, CHEST College, and WebMD.
A version of this article appeared on Medscape.com.
Beta-blockers are excellent drugs. They’re cheap and effective; feature prominently in hypertension guidelines; and remain a sine qua non for coronary artery disease, myocardial infarction, and heart failure treatment. They’ve been around forever, and we know they work. Good luck finding an adult medicine patient who isn’t on one.
Beta-blockers act by slowing resting heart rate (and blunting the heart rate response to exercise. The latter is a pernicious cause of activity intolerance that often goes unchecked. Even when the adverse effects of beta-blockers are appreciated, providers are loath to alter dosing, much less stop the drug. After all, beta-blockers are an integral part of guideline-directed medical therapy (GDMT), and GDMT saves lives.
Balancing Heart Rate and Stroke Volume Effects
To augment cardiac output and optimize oxygen uptake (VO2) during exercise, we need the heart rate response. In fact, the heart rate response contributes more to cardiac output than augmenting stroke volume (SV) and more to VO2 than the increase in arteriovenous (AV) oxygen difference. An inability to increase the heart rate commensurate with physiologic work is called chronotropic incompetence (CI). That’s what beta-blockers do ─ they cause CI.
Physiology dictates that CI will cause activity intolerance. That said, it’s hard to quantify the impact from beta-blockers at the individual patient level. Data suggest the heart rate effect is profound. A study in patients without heart failure found that 22% of participants on beta-blockers had CI, and the investigators used a conservative CI definition (≤ 62% of heart rate reserve used). A recent report published in JAMA Cardiology found that stopping beta-blockers in patients with heart failure allowed for an extra 30 beats/min at max exercise.
Wasserman and Whipp’s textbook, the last word on all things exercise, presents a sample subject who undergoes two separate cardiopulmonary exercise tests (CPETs). Before the first, he’s given a placebo, and before the second, he gets an intravenous beta-blocker. He’s a 23-year-old otherwise healthy male — the perfect test case for isolating beta-blocker impact without confounding by comorbid diseases, other medications, or deconditioning. His max heart rate dropped by 30 beats/min after the beta-blocker, identical to what we saw in the JAMA Cardiology study (with the heart rate increasing by 30 beats/min following withdrawal). Case closed. Stop the beta-blockers on your patients so they can meet their exercise goals and get healthy!
Such pithy enthusiasm discounts physiology’s complexities. When blunting our patient’s heart rate response with beta-blockers, we also increase diastolic filling time, which increases SV. For the 23-year-old in Wasserman and Whipp’s physiology textbook, the beta-blocker increased O2 pulse (the product of SV and AV difference). Presumably, this is mediated by the increased SV. There was a net reduction in VO2 peak, but it was nominal, suggesting that the drop in heart rate was largely offset by the increase in O2 pulse. For the patients in the JAMA Cardiology study, the entire group had a small increase in VO2 peak with beta-blocker withdrawal, but the effect differed by left ventricular function. Across different studies, the beta-blocker effect on heart rate is consistent but the change in overall exercise capacity is not.
Patient Variability in Beta-Blocker Response
In addition to left ventricular function, there are other factors likely to drive variability at the patient level. We’ve treated the response to beta-blockers as a class effect — an obvious oversimplification. The impact on exercise and the heart will vary by dose and drug (eg, atenolol vs metoprolol vs carvedilol, and so on). Beta-blockers can also affect the lungs, and we’re still debating how cautious to be in the presence of asthma or chronic obstructive pulmonary disease.
In a world of infinite time, resources, and expertise, we’d CPET everyone before and after beta-blocker use. Our current reality requires the unthinkable: We’ll have to talk to each other and our patients. For example, heart failure guidelines recommend titrating drugs to match the dose from trials that proved efficacy. These doses are quite high. Simple discussion with the cardiologist and the patient may allow for an adjustment back down with careful monitoring and close attention to activity tolerance. With any luck, you’ll preserve the benefits from GDMT while optimizing your patient›s ability to meet their exercise goals.
Dr. Holley, professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center, Washington, disclosed ties with Metapharm, CHEST College, and WebMD.
A version of this article appeared on Medscape.com.
Beta-blockers are excellent drugs. They’re cheap and effective; feature prominently in hypertension guidelines; and remain a sine qua non for coronary artery disease, myocardial infarction, and heart failure treatment. They’ve been around forever, and we know they work. Good luck finding an adult medicine patient who isn’t on one.
Beta-blockers act by slowing resting heart rate (and blunting the heart rate response to exercise. The latter is a pernicious cause of activity intolerance that often goes unchecked. Even when the adverse effects of beta-blockers are appreciated, providers are loath to alter dosing, much less stop the drug. After all, beta-blockers are an integral part of guideline-directed medical therapy (GDMT), and GDMT saves lives.
Balancing Heart Rate and Stroke Volume Effects
To augment cardiac output and optimize oxygen uptake (VO2) during exercise, we need the heart rate response. In fact, the heart rate response contributes more to cardiac output than augmenting stroke volume (SV) and more to VO2 than the increase in arteriovenous (AV) oxygen difference. An inability to increase the heart rate commensurate with physiologic work is called chronotropic incompetence (CI). That’s what beta-blockers do ─ they cause CI.
Physiology dictates that CI will cause activity intolerance. That said, it’s hard to quantify the impact from beta-blockers at the individual patient level. Data suggest the heart rate effect is profound. A study in patients without heart failure found that 22% of participants on beta-blockers had CI, and the investigators used a conservative CI definition (≤ 62% of heart rate reserve used). A recent report published in JAMA Cardiology found that stopping beta-blockers in patients with heart failure allowed for an extra 30 beats/min at max exercise.
Wasserman and Whipp’s textbook, the last word on all things exercise, presents a sample subject who undergoes two separate cardiopulmonary exercise tests (CPETs). Before the first, he’s given a placebo, and before the second, he gets an intravenous beta-blocker. He’s a 23-year-old otherwise healthy male — the perfect test case for isolating beta-blocker impact without confounding by comorbid diseases, other medications, or deconditioning. His max heart rate dropped by 30 beats/min after the beta-blocker, identical to what we saw in the JAMA Cardiology study (with the heart rate increasing by 30 beats/min following withdrawal). Case closed. Stop the beta-blockers on your patients so they can meet their exercise goals and get healthy!
Such pithy enthusiasm discounts physiology’s complexities. When blunting our patient’s heart rate response with beta-blockers, we also increase diastolic filling time, which increases SV. For the 23-year-old in Wasserman and Whipp’s physiology textbook, the beta-blocker increased O2 pulse (the product of SV and AV difference). Presumably, this is mediated by the increased SV. There was a net reduction in VO2 peak, but it was nominal, suggesting that the drop in heart rate was largely offset by the increase in O2 pulse. For the patients in the JAMA Cardiology study, the entire group had a small increase in VO2 peak with beta-blocker withdrawal, but the effect differed by left ventricular function. Across different studies, the beta-blocker effect on heart rate is consistent but the change in overall exercise capacity is not.
Patient Variability in Beta-Blocker Response
In addition to left ventricular function, there are other factors likely to drive variability at the patient level. We’ve treated the response to beta-blockers as a class effect — an obvious oversimplification. The impact on exercise and the heart will vary by dose and drug (eg, atenolol vs metoprolol vs carvedilol, and so on). Beta-blockers can also affect the lungs, and we’re still debating how cautious to be in the presence of asthma or chronic obstructive pulmonary disease.
In a world of infinite time, resources, and expertise, we’d CPET everyone before and after beta-blocker use. Our current reality requires the unthinkable: We’ll have to talk to each other and our patients. For example, heart failure guidelines recommend titrating drugs to match the dose from trials that proved efficacy. These doses are quite high. Simple discussion with the cardiologist and the patient may allow for an adjustment back down with careful monitoring and close attention to activity tolerance. With any luck, you’ll preserve the benefits from GDMT while optimizing your patient›s ability to meet their exercise goals.
Dr. Holley, professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center, Washington, disclosed ties with Metapharm, CHEST College, and WebMD.
A version of this article appeared on Medscape.com.
Narcolepsy an Independent Cardiovascular Disease Risk Factor
HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.
A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.
“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.
“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.
They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
Independent Risk Factor
The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.
This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.
Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.
Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).
They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).
The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.
In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.
“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.
They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.
“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.
“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
Compelling Evidence for Higher CVD
Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.
“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.
“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.
Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.
“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.
The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.
A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.
“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.
“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.
They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
Independent Risk Factor
The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.
This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.
Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.
Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).
They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).
The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.
In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.
“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.
They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.
“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.
“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
Compelling Evidence for Higher CVD
Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.
“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.
“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.
Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.
“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.
The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
HOUSTON — Narcolepsy is associated with a significantly increased risk for cardiovascular disease (CVD) and major adverse cardiac events (MACEs), independent of common comorbid conditions and medications commonly used to treat the chronic sleep disorder, according to two new studies.
A nationwide analysis revealed that people with narcolepsy had a 77% higher risk for CVD and an 82% higher risk for MACE than those without the disorder.
“These findings indicate that it is important for clinicians to regularly monitor patients for cardiovascular disease and take this into consideration when recommending specific treatments for narcolepsy,” study investigators Christopher Kaufmann, PhD; Munaza Riaz, PharmD, MPhil; and Rakesh Bhattacharjee, MD, told this news organization.
“Additionally, physicians should consider monitoring the presence of other health conditions as contributing factors to the risk of CVD,” they said. Dr. Kaufmann and Dr. Riaz are with the University of Florida, Gainesville, Florida, and Dr. Bhattacharjee is with the University of California, San Diego.
They presented their research at SLEEP 2024: 38th Annual Meeting of the Associated Professional Sleep Societies.
Independent Risk Factor
The National Institute of Neurological Disorders and Stroke reports an estimated 125,000 to 200,000 people in the United States live with narcolepsy. The condition often coexists with other common health conditions including obstructive sleep apnea (OSA), diabetes, and other comorbidities, which can all contribute to the risk for CVD.
This raises doubt as to whether narcolepsy itself directly leads to CVD or if it is the result of these comorbid health conditions. Additionally, some medications used to treat narcolepsy carry their own cardiovascular risks.
Using the IBM MarketScan Commercial and Medicare supplemental databases, the researchers identified 34,562 adults with a diagnosis of narcolepsy and a propensity-matched comparison cohort of 100,405 adults without narcolepsy. The patients had a mean age of 40 years, and 62% were women.
Compared with adults without narcolepsy, those with the chronic sleep disorder that causes overwhelming daytime drowsiness had a 77% increased risk for any CVD (hazard ratio [HR], 1.77) and an 82% increased risk for MACE (HR, 1.82).
They also had an increased risk for stroke (HR, 2.04), heart failure or myocardial infarction (MI; HR, 1.64), and atrial fibrillation (HR, 1.58).
The results were similar in a separate analysis of the same population that also controlled for baseline use of stimulants, oxybates, and wake-promoting agents — medications commonly used to treat excessive daytime sleepiness associated with narcolepsy.
In this analysis, narcolepsy was associated with an 89% higher risk for CVD (HR, 1.89) and a 95% increased risk for MACE (HR, 1.95). The risk for any stroke (HR, 2.06), heart failure (HR, 1.90), atrial fibrillation (HR, 1.66), and MI (HR, 1.93) was also higher in those with narcolepsy.
“Our study found that even after considering the presence of health conditions like obstructive sleep apnea, diabetes, hypertension, hyperlipidemia, and even depression, as well as medication use, there still appears to be an independent relationship between narcolepsy and CVD,” the investigators said.
They cautioned that the mechanisms explaining the link between CVD and narcolepsy are unclear and warrant further study.
“Sleep fragmentation is a hallmark of narcolepsy, and it is speculated that this fragmentation, which may trigger disturbances in autonomic function, predisposes individuals to CVD. In rodent models, a possible link has been observed between hypocretin — a central neurotransmitter that is reduced or deficient in patients with narcolepsy — and atherosclerosis.
“However, it remains uncertain whether this is the primary mechanism related to CVD,” they commented.
Compelling Evidence for Higher CVD
Commenting on the findings for this news organization, Shaheen Lakhan, MD, a neurologist and researcher based in Miami, Florida, called for narcolepsy to be recognized as a significant contributor to higher CVD risk.
“Given the compelling evidence linking narcolepsy to a higher incidence of cardiovascular disease, it is crucial that narcolepsy be included in clinical guidelines and risk assessment tools alongside other known risk factors,” said Dr. Lakhan, who was not involved in this research.
“Physicians and health care providers should proactively address the increased cardiovascular risk associated with narcolepsy by incorporating preventive strategies and interventions into the management of patients with this condition,” Dr. Lakhan suggested.
Regular CVD screening, a healthier lifestyle, and targeted therapies could all decrease cardiac risk, Dr. Lakhan added.
“Ultimately, novel disease-modifying therapies for narcolepsy should target the core mechanisms driving the increased cardiovascular risk associated with this condition. By elucidating the specific biological pathways and developing targeted therapies that address the unique challenges faced by narcolepsy patients, we can effectively mitigate the risk,” Dr. Lakhan said.
The studies were funded by the Sleep Research Society Foundation. The authors and Dr. Lakhan had no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM SLEEP 2024
Is Semaglutide the ‘New Statin’? Not So Fast
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.
Calcium and CV Risk: Are Supplements and Vitamin D to Blame?
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.
Another Reason to Control Lp(a): To Protect the Kidneys Too
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.
Counting Steps or Watching the Clock for a Longer Life?
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.
Risk Screening Tool Helped Identify Pregnant Patients Previously Undiagnosed With CVD
SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”
The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.
“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.
Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.
“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.
The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.
The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.
Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.
Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.
Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.
During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.
Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.
This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.
“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”
*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.
*This study was updated on May 30, 2024.
SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”
The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.
“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.
Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.
“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.
The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.
The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.
Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.
Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.
Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.
During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.
Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.
This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.
“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”
*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.
*This study was updated on May 30, 2024.
SAN FRANCISCO — More than a quarter of pregnant or postpartum patients who screened positive for cardiovascular disease ended up with a cardiovascular disease diagnosis when providers used a risk screening tool built into the electronic medical records system for all patients, according to research presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists. “Timely diagnosis of cardiovascular disease is critical, though challenging, since pregnancy is a state of hemodynamic stress with symptoms that are like those of cardiovascular disease, and healthcare providers may not suspect cardiovascular disease in pregnant patients with symptoms of it,” Kevin Flatley, MD, a resident ob.gyn. at Montefiore Health System and the Albert Einstein College of Medicine in New York City, told attendees at the conference. “The cardiovascular risk assessment tool proved valuable for identifying and providing individualized care for cardio-obstetric patients.”
The study senior author, Diana S. Wolfe, MD, MPH, associate division director of Maternal Fetal Medicine at Montefiore Health System and associate professor of medicine in cardiology at Albert Einstein College of Medicine, said in an interview that cardiovascular risk in Montefiore’s urban population is significant.
“Cardiovascular disease risk screening identifies true cardiac disease in this population and can change the medical management and outcome of pregnant and postpartum patients,” Dr. Wolfe said. Screening has the potential to decrease maternal morbidity and mortality in our country, she said.
Dawnette Lewis, MD, MPH, director of the Center for Maternal Health at Northwell Health and an ob.gyn. and maternal fetal medicine specialist who was not involved in the study, was impressed with the research.
“We know that cardiovascular disease is one of the leading causes of maternal mortality,” Dr. Lewis said in an interview. “It is important to have an accurate risk assessment score, so I think what is being presented in this abstract is great.” She said she’s aware that other cardio-obstetric programs across the country are also implementing cardiovascular risk assessment tools during pregnancy.
The researchers built into their electronic health records a screening algorithm developed by the California Maternal Quality Care Initiative that had been based on a retrospective review of cardiovascular maternal deaths in California from 2002 to 2006. Their study aimed to identify the true positives — those who actually had cardiovascular disease — of those determined to be at risk by the screening toolkit.
The institution’s goal was for all patients to undergo a screening risk assessment at least once during prenatal and/or postpartum visits. Patients were considered to screen positive if they had at least one symptom, at least one vital sign abnormality, and at least one risk factor, or any combination of these that added up to 4.
Symptoms in the screening tool included shortness of breath, shortness of breath while lying flat, a rapid heart rate, asthma that was unresponsive to therapy, palpitations, fainting or other loss of consciousness, and chest pain. Abnormal vital signs included a resting heart rate of 110 bpm or greater, systolic blood pressure of 140 mm Hg or higher, a respiratory rate of 24 or higher, and an oxygen saturation of 96% or lower.
Risk factors included being 40 or older, being Black, having a pre-pregnancy BMI of 35 or greater, preexisting diabetes, hypertension, substance use, and a history of cancer, chemotherapy, or chest radiation. “Current practice acknowledges that the risk factor currently included in the algorithm of self-identified as Black actually represents racism, bias, and social determinants of health, known risk factors for CVD,” Wolfe said.
Patients who screened positive underwent an echocardiogram, a cardio-obstetric consultation, and an additional work-up.
During the June 2022–September 2023 study period, 148 out of 1877 screened patients (7.9%) had a positive screen. Of these, 108 were false positives and 40 (27%) were true positives. The number of true false positives is not known because many women did not come for their workups.* The true positives mostly included patients with mild valvular disease, but about a quarter had mild, moderate, or severe ventricular dilation or hypertrophy and a little less than a quarter were positive for systolic or diastolic dysfunction.
Most (72.5%) of the 40 true-positive cases needed a multidisciplinary cardio-obstetrics team plan, and 11 patients (27.5%) needed follow-up and had multiple visits with the cardio-obstetrics team. Six of the true-positive cases (15%) “were deemed to be of higher risk for decompensation during labor and required detailed plans for intrapartum and postpartum management,” the researchers reported. Nine patients (22.5%) began new cardiovascular medications.
This research is a validation study of the current algorithm, Wolfe said, and the algorithm will be revised based on the results of the completed validation study.
“The objective is universal cardiovascular risk screening for all pregnant and postpartum persons in the US,” Wolfe said. “Once the data collection from this validation study is concluded, our goal is to disseminate a revised CVD risk screening tool that can be implemented into the electronic medical records of all institutions in our country.”
*The study partially funded by the National Institute of Child Health and Human Development award #5R21HD101783. All the authors and Dr. Lewis had no disclosures. Dr. Afshan B. Hameed of the University of California at Irvine was a partner in the study.
*This study was updated on May 30, 2024.
FROM ACOG 2024
Statins Show ‘Remarkable’ CVD Benefit in Oldest Patients
Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.
“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.
Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
Little Consensus on Statins for This Age Group
Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.
Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.
Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.
Risk Reduction Seen in Both Senior Groups
Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.
In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.
Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.
One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.
Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”
Numbers Needed to Treat Are Strikingly Low
He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.
The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”
For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”
Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.
He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.
Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.
“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.
“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”
The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.
Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.
“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.
Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
Little Consensus on Statins for This Age Group
Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.
Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.
Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.
Risk Reduction Seen in Both Senior Groups
Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.
In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.
Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.
One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.
Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”
Numbers Needed to Treat Are Strikingly Low
He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.
The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”
For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”
Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.
He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.
Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.
“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.
“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”
The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.
Patients at least 75 years old saw a reduced risk of overall cardiovascular incidence with statin therapy without increased risk of severe adverse effects in a study published in Annals of Internal Medicine.
“Of note, the benefits and safety of statin therapy were consistently found in adults aged 85 years or older,” wrote the authors, led by Wanchun Xu, a PhD student with the Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, in the Special Administrative Region, China.
Geriatrician Jerry H. Gurwitz, MD, the Dr. John Meyers Professor in Primary Care Medicine at UMass Chan Medical School in Boston, said he found the results of this trial “remarkable,” but is awaiting the results of the much-anticipated randomized, controlled PREVENTABLE trial years from now for more definitive evidence.
Little Consensus on Statins for This Age Group
Prescribing statins for primary prevention of CVD in the most senior patient groups has been controversial. There is little consensus as patients in this age group have been underrepresented in randomized controlled trials.
Major guidelines for use of statins in the primary prevention of CVD, including the US Preventive Services Task Force, exclude specific guidance for statin use in patients older than 75, citing insufficient evidence.
Ms. Xu and colleagues used territory-wide electronic health records in a sequential target trial emulation comparing matched cohorts that did or did not start statins. There were 42,680 matched person-trials in the group of patients aged 75-84 years and 5,390 matched person-trials in the 85 and older group. The average follow-up was 5.3 years and people with CVDs at baseline, such as coronary heart disease, were excluded. Patients who met indications for statin initiation from January 2008 to December 2015 were included.
Risk Reduction Seen in Both Senior Groups
Of the 42,680 matched person-trials in the 75-84 age group, 9676 developed cardiovascular disease; of the 5390 in the 85-plus group, 1600 developed CVD.
In the younger cohort, the 5-year reduced risk for overall CVD incidence when statin therapy was initiated was 1.20% (95% CI, 0.57%-1.82%) in the intention-to-treat (ITT) analysis; 5.00% (95% CI, 1.11%-8.89%) in the per protocol (PP) analysis.
Reduced risk for overall CVD incidence in the 85-and-older group when statins were initiated was 4.44% in the ITT analysis (95% CI, 1.40%-7.48%); and 12.50% in the PP analysis (95% CI, 4.33%-20.66%). There was no significantly increased risk for liver dysfunction or myopathies in either age group, the authors stated.
One of the biggest strengths of the study is the use of population-based data over a long period. One of the limitations was that the researchers were not able to measure lifestyle factors such as diet and physical activity in their analysis.
Dr. Gurwitz, who has done drug research in older adults for decades, said “the results are very compelling,” and in the oldest group “almost too compelling. Wow.”
Numbers Needed to Treat Are Strikingly Low
He noted that the authors thoroughly acknowledge limitations of the trial. But he also pointed to the impressive number needed to treat reported by the researchers.
The authors stated: “[O]n the basis of the estimated absolute risk reduction in the PP analysis, the number needed to treat [NNT] to prevent 1 CVD event in 5 years was 20 (95% CI, 11-90) in those aged 75-84 years and 8 (95% CI, 5-23) in those aged 85 years or older.”
For perspective, he said, “Sometimes you’re seeing numbers needed to treat for vaccinations of 400 to prevent one hospitalization. They are using real-world information and they are seeing this remarkable effect. If it’s that good in the real world, it’s going to be even better in a clinical trial. That’s why I have some reservations about whether it’s really that good.”
Dr. Gurwitz said, “I’m not ready to start an 87-year-old on statin therapy who hasn’t been on it before for primary prevention, despite the results of this very well done study.” He will await the findings of PREVENTABLE, which aims to enroll 20,000 people at least 75 years old to look at statin use. But in the meantime, he will discuss the Xu et al. results and other evidence with patients if they request statins and may prescribe them as part of shared decision making.
He said the question of whether to use statins in primary prevention is similar to the question of whether to use aspirin as primary prevention for CVD in older adults.
Originally, “Most of us thought, yes, it’s probably a good thing,” he said, but now “there have been a lot of deprescribing efforts to get older people off of aspirin.
“In the United States, believe it or not, 48% of people 75 and older are on statins already,” Dr. Gurwitz said. “Maybe that’s good,” he said, but added physicians won’t know for sure until PREVENTABLE results are in.
“If I didn’t already know the PREVENTABLE trial was going on, and it was never going to happen, I would find this [Xu et al. study] very influential,” Dr. Gurwitz said. “I’m willing to wait.”
The study was funded by the Health and Medical Research Fund, Health Bureau, the Government of Hong Kong Special Administrative Region, China, and the National Natural Science Foundation of China. Coauthors reported grants from the Kerry Group Kuok Foundation, the Malaysian College of Family Physicians, and the International Association of Chinese Nephrologists in Hong Kong. Dr. Gurwitz reported no relevant financial relationships.
FROM ANNALS OF INTERNAL MEDICINE
What Health Risks Do Microplastics Pose?
The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.
Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.
Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.
The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.
The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
MNP Exposure
MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 105 particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.
MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
MNP and Biologic Systems
The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.
A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
Between Risk and Toxicity
MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.
MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.
The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.
However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
Future Scenarios
Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.
The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.
The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”
This story was translated from Univadis Italy, which is part of the Medscape professional network, 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.
The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.
Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.
Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.
The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.
The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
MNP Exposure
MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 105 particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.
MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
MNP and Biologic Systems
The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.
A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
Between Risk and Toxicity
MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.
MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.
The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.
However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
Future Scenarios
Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.
The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.
The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”
This story was translated from Univadis Italy, which is part of the Medscape professional network, 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.
The annual production of plastic worldwide has increased exponentially from about 2 million tons in 1950 to 460 million tons in 2019, and current levels are expected to triple by 2060.
Plastic contains more than 10,000 chemicals, including carcinogenic substances and endocrine disruptors. Plastic and associated chemicals are responsible for widespread pollution, contaminating aquatic (marine and freshwater), terrestrial, and atmospheric environments globally.
Atmospheric concentrations of plastic particles are on the rise, to the extent that in a remote station in the Eastern Alps in Austria, the contribution of micro- and nanoplastics (MNPs) to organic matter was comparable to data collected at an urban site.
The ocean is the ultimate destination for much of the plastic. All oceans, on the surface and in the depths, contain plastic, which is even found in polar sea ice. Many plastics seem to resist decomposition in the ocean and could persist in the environment for decades. Macro- and microplastic (MP) particles have been identified in hundreds of marine species, including species consumed by humans.
The quantity and fate of MP particles (> 10 µm) and smaller nanoplastics (< 10 µm) in aquatic environments are poorly understood, but what is most concerning is their ability to cross biologic barriers and the potential harm associated with their mobility in biologic systems.
MNP Exposure
MNPs can originate from a wide variety of sources, including food, beverages, and food product packaging. Water bottles represent a significant source of ingestible MNPs for people in their daily lives. Recent estimates, using stimulated Raman scattering imaging, documented a concentration of MNP of approximately 2.4 ± 1.3 × 105 particles per liter of bottled water. Around 90% are nanoplastics, which is two to three orders of magnitude higher than previously reported results for larger MPs.
MNPs enter the body primarily through ingestion or inhalation. For example, MNPs can be ingested by drinking liquids or eating food that has been stored or heated in plastic containers from which they have leaked or by using toothpaste that contains them. Infants are exposed to MPs from artificial milk preparation in polypropylene baby bottles, with higher levels than previously detected and ranging from 14,600 to 4,550,000 particles per capita per day.
MNP and Biologic Systems
The possible formation of hetero-aggregates between nanoplastics and natural organic matter has long been recognized as a potential challenge in the analysis of nanoplastics and can influence toxicologic results in biologic exposure. The direct visualization of such hetero-aggregates in real-world samples supports these concerns, but the analysis of MNPs with traditional techniques remains challenging. Unlike engineered nanoparticles (prepared in the laboratory as model systems), the nanoplastics in the environment are label-free and exhibit significant heterogeneity in chemical composition and morphology.
A systematic analysis of evidence on the toxic effects of MNPs on murine models, however, showed that 52.78% of biologic endpoints (related to glucose metabolism, reproduction, oxidative stress, and lipid metabolism) were significantly affected by MNP exposure.
Between Risk and Toxicity
MNP can enter the body in vivo through the digestive tract, respiratory tract, and skin contact. On average, humans could ingest from 0.1 to 5 g of MNP per week through various exposure routes.
MNPs are a potential risk factor for cardiovascular diseases, as suggested by a recent study on 257 patients with carotid atheromatous plaques. In 58.4% of cases, polyvinyl chloride was detected in the carotid artery plaque, with an average level of 5.2 ± 2.4 μg/mg of plaque. Patients with MNPs inside the atheroma had a higher risk (relative risk, 4.53) for a composite cardiovascular event of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than participants where MNPs were not detectable inside the atheromatous plaque.
The potential link between inflammatory bowel disease (IBD) and MPs has been hypothesized by a study that reported a higher fecal MP concentration in patients with IBD than in healthy individuals. Fecal MP level was correlated with disease severity.
However, these studies have not demonstrated a causal relationship between MNPs and disease, and the way MNPs may influence cellular functions and induce stress responses is not yet well understood.
Future Scenarios
Current evidence confirms the fragmentation of plastic beyond the micrometer level and has unequivocally detected nanoplastics in real samples. As with many other particle distributions of the same size in the natural world, there are substantially more nanoplastics, despite their invisibility with conventional imaging techniques, than particles larger than the micron size.
The initial results of studies on MNPs in humans will stimulate future research on the amounts of MNPs that accumulate in tissue over a person’s lifetime. Researchers also will examine how the particles’ characteristics, including their chemical composition, size, and shape, can influence organs and tissues.
The way MNPs can cause harm, including through effects on the immune system and microbiome, will need to be clarified by investigating possible direct cytotoxic effects, consistent with the introductory statement of the Organization for Economic Cooperation and Development global policy forum on plastics, which states, “Plastic pollution is one of the great environmental challenges of the 21st century, causing wide-ranging damage to ecosystems and human health.”
This story was translated from Univadis Italy, which is part of the Medscape professional network, 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.