Cardiology News

Physicians are leaving healthcare in droves, “not because they don’t want to practice ... but because the system is making it more and more difficult for them to care for their patients,” Bruce Scott, MD, president-elect of the American Medical Association (AMA), said at a press conference May 9 at the National Rural Health Association’s Annual Conference in New Orleans. 

He said that shrinking reimbursement rates and excessive administrative tasks are pushing doctors out of the workforce, exacerbating physician shortages in rural locations where 46 million Americans live. 

Rural areas have about one tenth of the specialists that urban areas do, and 65% of rural communities do not have enough primary care doctors, according to federal data. A recent Centers for Disease Control and Prevention report found that people living in rural areas are more likely to die early from preventable causes than their urban counterparts, said Dr. Scott. 

He said the AMA wants Congress to pass legislation to incentivize more physicians to work in rural areas and expand the number of rural and primary care residency spots. Historically, 80% of residents practice within 80 miles of where they complete residency, he said. 

Dr. Scott also hopes Congress will revise the J-1 visa rules to allow qualified international medical graduates to continue to practice in the United States. He’d like to see the pandemic telehealth flexibilities made permanent because these loosened guidelines greatly improved care access for rural areas in recent years. 

Lower Pay Affects Care in Rural, Urban Areas

Decreased reimbursements also have hit rural and urban doctors in independent practice particularly hard, Dr. Scott said. When adjusted for inflation, the current Medicare payment rate for physicians has dropped 29% since 2001, he said. Now that commercial payers tie their reimbursement models to the Medicare rate, physicians are experiencing “severe” financial stress amid rising practice costs and student loan debt. 

He shared anecdotes about how these issues have affected his private otolaryngology practice in Louisville, Kentucky, a state where more than 2 million people live in federally designated primary care professional shortage areas. 

“A major insurance company that controls over 60% of the private payer market in rural Kentucky [recently] offered us ... surgical rates less than they paid us 6 years ago,” he said. 

Dr. Scott said physicians must make difficult choices. “Do we not invest in the latest physical equipment? Do we reduce our number of employees? Do we perhaps stop accepting new Medicare patients?”

He noted that physicians now spend twice as much time on prior authorizations and other administrative tasks as they do on direct patient care. According to a 2022 AMA survey, 33% of physicians reported that the cumbersome prior authorization process led to a serious adverse event for a patient. Eighty percent reported it caused their patient to forgo treatment altogether.

Dr. Scott, who will be sworn in as AMA president in June, said he experiences the frustration daily. 

“I have to get on the phone and justify to an insurance person who rarely has gone to medical school, has never seen the patient, and heck, in my case, sometimes they can’t even say otolaryngology, much less tell me what the appropriate care is for my patient,” he said.

When asked about the impact of private equity in healthcare, Dr. Scott said there is room for all different modes of practice, but private equity could bring a unique benefit. 

“They have deeper pockets to potentially invest in telehealth technology, AI, and better computer systems,” he said. 

But, he said, some private equity-owned systems have abandoned rural areas, and in other regions they “push the physicians to move faster, see more patients, and do the things that are profit-driven.

“The key is to continue to provide ... quality medical care that is determined by an individual physician in consultation with the patient.”
 

A version of this article appeared on Medscape.com.

Physicians are leaving healthcare in droves, “not because they don’t want to practice ... but because the system is making it more and more difficult for them to care for their patients,” Bruce Scott, MD, president-elect of the American Medical Association (AMA), said at a press conference May 9 at the National Rural Health Association’s Annual Conference in New Orleans. 

He said that shrinking reimbursement rates and excessive administrative tasks are pushing doctors out of the workforce, exacerbating physician shortages in rural locations where 46 million Americans live. 

Rural areas have about one tenth of the specialists that urban areas do, and 65% of rural communities do not have enough primary care doctors, according to federal data. A recent Centers for Disease Control and Prevention report found that people living in rural areas are more likely to die early from preventable causes than their urban counterparts, said Dr. Scott. 

He said the AMA wants Congress to pass legislation to incentivize more physicians to work in rural areas and expand the number of rural and primary care residency spots. Historically, 80% of residents practice within 80 miles of where they complete residency, he said. 

Dr. Scott also hopes Congress will revise the J-1 visa rules to allow qualified international medical graduates to continue to practice in the United States. He’d like to see the pandemic telehealth flexibilities made permanent because these loosened guidelines greatly improved care access for rural areas in recent years. 

Lower Pay Affects Care in Rural, Urban Areas

Decreased reimbursements also have hit rural and urban doctors in independent practice particularly hard, Dr. Scott said. When adjusted for inflation, the current Medicare payment rate for physicians has dropped 29% since 2001, he said. Now that commercial payers tie their reimbursement models to the Medicare rate, physicians are experiencing “severe” financial stress amid rising practice costs and student loan debt. 

He shared anecdotes about how these issues have affected his private otolaryngology practice in Louisville, Kentucky, a state where more than 2 million people live in federally designated primary care professional shortage areas. 

“A major insurance company that controls over 60% of the private payer market in rural Kentucky [recently] offered us ... surgical rates less than they paid us 6 years ago,” he said. 

Dr. Scott said physicians must make difficult choices. “Do we not invest in the latest physical equipment? Do we reduce our number of employees? Do we perhaps stop accepting new Medicare patients?”

He noted that physicians now spend twice as much time on prior authorizations and other administrative tasks as they do on direct patient care. According to a 2022 AMA survey, 33% of physicians reported that the cumbersome prior authorization process led to a serious adverse event for a patient. Eighty percent reported it caused their patient to forgo treatment altogether.

Dr. Scott, who will be sworn in as AMA president in June, said he experiences the frustration daily. 

“I have to get on the phone and justify to an insurance person who rarely has gone to medical school, has never seen the patient, and heck, in my case, sometimes they can’t even say otolaryngology, much less tell me what the appropriate care is for my patient,” he said.

When asked about the impact of private equity in healthcare, Dr. Scott said there is room for all different modes of practice, but private equity could bring a unique benefit. 

“They have deeper pockets to potentially invest in telehealth technology, AI, and better computer systems,” he said. 

But, he said, some private equity-owned systems have abandoned rural areas, and in other regions they “push the physicians to move faster, see more patients, and do the things that are profit-driven.

“The key is to continue to provide ... quality medical care that is determined by an individual physician in consultation with the patient.”
 

A version of this article appeared on Medscape.com.

Physicians are leaving healthcare in droves, “not because they don’t want to practice ... but because the system is making it more and more difficult for them to care for their patients,” Bruce Scott, MD, president-elect of the American Medical Association (AMA), said at a press conference May 9 at the National Rural Health Association’s Annual Conference in New Orleans. 

He said that shrinking reimbursement rates and excessive administrative tasks are pushing doctors out of the workforce, exacerbating physician shortages in rural locations where 46 million Americans live. 

Rural areas have about one tenth of the specialists that urban areas do, and 65% of rural communities do not have enough primary care doctors, according to federal data. A recent Centers for Disease Control and Prevention report found that people living in rural areas are more likely to die early from preventable causes than their urban counterparts, said Dr. Scott. 

He said the AMA wants Congress to pass legislation to incentivize more physicians to work in rural areas and expand the number of rural and primary care residency spots. Historically, 80% of residents practice within 80 miles of where they complete residency, he said. 

Dr. Scott also hopes Congress will revise the J-1 visa rules to allow qualified international medical graduates to continue to practice in the United States. He’d like to see the pandemic telehealth flexibilities made permanent because these loosened guidelines greatly improved care access for rural areas in recent years. 

Lower Pay Affects Care in Rural, Urban Areas

Decreased reimbursements also have hit rural and urban doctors in independent practice particularly hard, Dr. Scott said. When adjusted for inflation, the current Medicare payment rate for physicians has dropped 29% since 2001, he said. Now that commercial payers tie their reimbursement models to the Medicare rate, physicians are experiencing “severe” financial stress amid rising practice costs and student loan debt. 

He shared anecdotes about how these issues have affected his private otolaryngology practice in Louisville, Kentucky, a state where more than 2 million people live in federally designated primary care professional shortage areas. 

“A major insurance company that controls over 60% of the private payer market in rural Kentucky [recently] offered us ... surgical rates less than they paid us 6 years ago,” he said. 

Dr. Scott said physicians must make difficult choices. “Do we not invest in the latest physical equipment? Do we reduce our number of employees? Do we perhaps stop accepting new Medicare patients?”

He noted that physicians now spend twice as much time on prior authorizations and other administrative tasks as they do on direct patient care. According to a 2022 AMA survey, 33% of physicians reported that the cumbersome prior authorization process led to a serious adverse event for a patient. Eighty percent reported it caused their patient to forgo treatment altogether.

Dr. Scott, who will be sworn in as AMA president in June, said he experiences the frustration daily. 

“I have to get on the phone and justify to an insurance person who rarely has gone to medical school, has never seen the patient, and heck, in my case, sometimes they can’t even say otolaryngology, much less tell me what the appropriate care is for my patient,” he said.

When asked about the impact of private equity in healthcare, Dr. Scott said there is room for all different modes of practice, but private equity could bring a unique benefit. 

“They have deeper pockets to potentially invest in telehealth technology, AI, and better computer systems,” he said. 

But, he said, some private equity-owned systems have abandoned rural areas, and in other regions they “push the physicians to move faster, see more patients, and do the things that are profit-driven.

“The key is to continue to provide ... quality medical care that is determined by an individual physician in consultation with the patient.”
 

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

Like it or not, artificial intelligence (AI) is coming to medicine. For many physicians — maybe you — it’s already here.

More than a third of physicians use AI in their practice. And the vast majority of healthcare companies — 94%, according to Morgan Stanley — use some kind of AI machine learning.

“It’s incumbent on physicians, as well as physicians in training, to become familiar with at least the basics [of AI],” said internist Matthew DeCamp, MD, PhD, an associate professor in the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Understanding AI can help you leverage it safely and effectively — plus “make better-informed decisions about whether or not to use it in [your] practice,” Dr. DeCamp said.

“Frankly, the people who are deciding whether to implement algorithms in our day-to-day lives are oftentimes not physicians,” noted Ravi B. Parikh, MD, an assistant professor at the University of Pennsylvania and director of augmented and artificial intelligence at the Penn Center for Cancer Care Innovation, Philadelphia. Yet, physicians are most qualified to assess an AI tool’s usefulness in clinical practice.

That brings us to the best starting place for your AI education: Your own institution. Find out what AI tools your organization is implementing — and how you can influence them.

“Getting involved with our hospital data governance is the best way not only to learn practically what these AI tools do but also to influence the development process in positive ways,” Dr. Parikh said.

From there, consider the following resources to enhance your AI knowledge.
 

Get a Lay of the Land: Free Primers

Many clinical societies and interest groups have put out AI primers, an easy way to get a broad overview of the technology. The following were recommended or developed by the experts we spoke to, and all are free:

• The American Medical Association’s (AMA’s) framework for advancing healthcare AI lays out actionable guidance. Ask three key questions, the AMA recommends: Does it work? Does it work for my patients? Does it improve health outcomes?
• The Coalition for Health AI’s Blueprint for Trustworthy AI Implementation Guidance and Assurance for Healthcare provides a high-level summary of how to evaluate AI in healthcare, plus steps for implementing it. AI systems should be useful, safe, accountable, explainable, fair, and secure, the report asserted.
• The National Academy of Medicine’s draft code of conduct for AI in healthcare proposes core principles and commitments. These “reflect simple guideposts to guide and gauge behavior in a complex system and provide a starting point for real-time decision-making,” the report said.
• Health AI Partnership — a collaboration of Duke Health and Microsoft — outlines eight key decision points to consider at any stage of AI implementation, whether you’re still planning how to use it or you’ve started but want to improve it. The site also provides a breakdown of standards by regulatory agencies, organizations, and oversight bodies — so you can make sure your practices align with their guidance.

Make the Most of Conferences

Next time you’re at a conference, check the agenda for sessions on AI. “For someone who’s interested in this, I would be looking for content in my next national meeting because, undoubtedly, it’s going to be there,” said Dr. DeCamp. In a fast-moving field like AI, it’s a great way to get fresh, up-to-the-moment insights.

Listen to This Podcast

The New England Journal of Medicine’s free monthly podcast AI Grand Rounds is made for researchers and clinicians. Available on Apple, Spotify, and YouTube, the pod is good for “someone who’s looking to see both where the field is going [and to hear] a retrospective on big-name papers,” said Dr. Parikh . Episodes run for about an hour.

To learn about the challenges of applying AI to biology: Listen to Daphne Koller, PhD, founder of AI-driven drug discovery and development company insitro. For insights on the potential of AI in medicine, tune into the one with Eric Horvitz, MD, PhD, Microsoft’s chief scientific officer.
 

Consider a Class

Look for courses that focus on AI applications in clinical practice rather than a deep dive into theory. (You need to understand how these tools will influence your work, not the intricacies of large language model development.) Be wary of corporate-funded training that centers on one product , which could present conflicts of interest, said Dr. DeCamp. See the chart for courses that meet these criteria.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Nearly 90% of adults were at risk of developing cardiovascular-kidney-metabolic (CKM) syndrome between 2011 and 2020, according to new research published in JAMA.

METHODOLOGY:

• In 2023, the American Heart Association defined  to acknowledge how heart and kidney diseases, diabetes, and obesity interact and are increasingly co-occurring conditions.
• Researchers used data from the National Health and Nutrition Examination Survey between 2011 and 2020.
• More than 10,000 adults over age 20 years were included; all of them received a physical and fasting laboratory measurements and self-reported their cardiovascular disease (CVD) status.
• Researchers created categories for risk, ranging from 0 (no risk factors) to 4, using factors such as kidney disease, obesity, and hypertension.

TAKEAWAY:

• Nearly 90% of participants met the criteria for having a stage of the CKM syndrome, with rates remaining steady throughout the study period.Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.
• Almost half of people met the criteria for stage 2 (having metabolic risk factors like hypertension or moderate- to high-risk chronic kidney disease).
   
• 14.6% met the criteria for advanced stage 3 (very high-risk chronic kidney disease or a high risk for 10-year CVD) and stage 4 CKM syndrome (established CVD) combined.
   
• Men, adults over age 65 years, and Black individuals were at a greater risk for advanced stages of the CKM syndrome.

IN PRACTICE:

“Equitable health care approaches prioritizing CKM health are urgently needed,” the study authors wrote.

SOURCE:

The study was led by Muthiah Vaduganathan, MD, MPH, cardiologist and researcher at Brigham and Women’s Hospital, Harvard Medical School, Boston.

LIMITATIONS: 

Established CVD statuses were self-reported. Some data that would indicate advanced CKM stages were not available (eg, cardiac biomarkers, echocardiography, and coronary angiography), which may have led to an underestimation of rates.

DISCLOSURES:

One author received grants from Bristol Myers Squibb–Pfizer outside the submitted work. Dr. Vaduganathan received grants from and was an adviser and committee trial member for various pharmaceutical companies outside the submitted work. The authors reported no other disclosures.

A version of this article appeared on Medscape.com.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

A plastic surgeon broke federal law when he restricted patients from posting negative reviews by requiring them to sign nondisclosure agreements before they received care, a district judge has ruled.

Seattle-based surgeon Javad Sajan, MD, ran afoul of the Consumer Review Fairness Act (CRFA) by requiring more than 10,000 patients to sign the agreements, according to a recent decision by US District Judge Ricardo S. Martinez. The law protects consumers’ rights to post truthful reviews about businesses. 

Judge Martinez wrote that the terms of Dr. Sajan’s nondisclosure agreements “clearly include language prohibiting or restricting patients from posting negative reviews,” in violation of CRFA. Penalties for the offense will be determined at a September trial. 

This news organization contacted Dr. Sajan’s office and his attorney for comment but did not get a response. 

The decision is the latest development in an ongoing legal dispute between Dr. Sajan and the State of Washington over whether the surgeon’s efforts to limit negative online reviews were illegal. 

Beginning in 2017, Dr. Sajan and his practice, Allure Esthetic, introduced agreements that “forced” patients to contact the business directly if they had concerns rather than post a negative review, according to a 2022 lawsuit against Dr. Sajan filed by Washington Attorney General Robert Ferguson. 

“Online reviews are often the first stop when consumers are determining who to trust,” Mr. Ferguson said in a statement. “That’s especially critical when those services deal with a patient’s health and safety. We will take action against those who illegally stop Washingtonians from sharing reviews with the public.”

If patients posted negative reviews, the clinic, in some cases, threatened litigation, according to the complaint. In other cases, patients were allegedly offered money and free services in exchange for taking the reviews down. Patients who accepted cash or services were required to sign a second agreement forbidding them from posting future negative reviews and imposing a $250,000 penalty for failure to comply, according to court documents. 

In court documents, Dr. Sajan’s attorneys argued the agreements did not violate CRFA because patients had the opportunity to modify the language or decline signing them, which hundreds did. The CRFA requires Mr. Ferguson to prove that consumers lacked a meaningful opportunity to negotiate the terms, attorneys for Dr. Sajan argued in court records. 

But Judge Martinez wrote that the patients who declined to sign the agreements or changed the terms represented only a “tiny fraction” of the affected patients.

The agreement language restricts patients from speaking out by forcing dissatisfied patients to work with Allure until a resolution is reached, Judge Martinez noted in his decision. “At the very least, this would delay patients from posting such reviews and force patients to interact in some way with Allure, and it certainly appears to prohibit posting reviews until Allure agrees to some kind of favorable resolution.”
 

Surgeon Posted Fake Positive Reviews to Counteract Bad Reviews, AG Says

Employee accounts in court documents describe a physician fixated on reviews who went to great lengths to ensure positive reviews about his work outweighed the negative. 

Former employees said they were instructed to track down patients who left negative reviews and either “threaten” them to take the posts down or offer them “money” or other things, according to Mr. Ferguson’s lawsuit. If patients could not be identified, the practice would file a defamation lawsuit against the anonymous person who posted the review and use litigation to subpoena the website for the reviewer’s IP address in order to identify them, according to court documents. 

Employees testified they had regular meetings to review current negative reviews and discuss what steps they were taking to get them removed. At team meetings, in-house counsel would regularly present an Excel spreadsheet with updates on progress in getting patients to remove negative reviews, according to court documents. 

In addition to restricting negative reviews, Mr. Ferguson accuses Dr. Sajan of posting fake positive reviews and “buying” thousands of fake followers on social media. 

At Dr. Sajan’s direction, employees created Gmail accounts using stock photos for their profile pictures and used the accounts to post fake reviews of Allure Esthetic and Dr. Sajan, according to the complaint. The practice also used members of an online forum called BlackHatWorld.com to create fake email accounts and to post fake reviews, the attorney general alleges. Many of the fake positive reviews, including the fake Google reviews, still appear on online review sites today, the attorney general contends. 

Dr. Sajan and his practice also allegedly manipulated social media to appear more popular. Mr. Ferguson claims that Dr. Sajan instructed his former web designer to purchase 60,000 followers through a vendor on BlackHatWorld.com. Most of Dr. Sajan’s current Instagram followers are not real, according to Mr. Ferguson. 

The practice also used a social media bot tool to buy thousands of fake likes on Instagram, YouTube, and other social media, according to court documents. 

In addition, Dr. Sajan and his practice are accused of significantly altering “before and after” photos of patients and using fake email accounts to allow the clinic to take skincare rebates intended for patients.

All of these practices violated HIPAA, the state Consumer Protection Act (CPA) and the federal CRFA, according to Mr. Ferguson. 
 

Surgeon Claims Competitor Behind Allegations 

Attorneys for Dr. Sajan argue a competitor is behind the accusations and that other regulatory entities determined the practice did nothing wrong. 

The competitor, a Seattle-based plastic surgeon, filed numerous complaints about Dr. Sajan to the Washington Medical Commission (WMC), according to court documents. The medical commission reviewed the third agreement and closed its investigation, finding that if the allegations were true, “no violation of law occurred,” court records show. 

“Defendants relied upon this closing code from the WMC that the (non-disclosure) forms were lawful,” Dr. Sajan’s attorneys wrote in court documents.

The US Department of Health & Human Services Office for Civil Rights (OCR) also reviewed and audited Dr. Sajan’s use of the agreements, his attorneys noted. In a notice from OCR included in court exhibits, the agency wrote that all matters at issue have now been resolved through the practice’s voluntary compliance actions and that it was closing its investigation. 

Attorneys for Dr. Sajan accuse Mr. Ferguson and state investigators of withholding the full extent of the competitor’s involvement in their investigation and failing to identify the competitor in written discovery or any of its initial disclosures. Dr. Sajan and his team discovered that the competitor was a source of key information through public records requests, according to court documents. 

The remaining claims against Dr. Sajan will be addressed at trial, set for September 9, 2024. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

A large international cohort study identified a higher risk for cardiovascular diseases and mortality in patients with prurigo nodularis (PN), particularly among women and White patients.

METHODOLOGY:

• Studies have shown increased risks for cardiovascular diseases in patients with PN, but limited sample sizes have hindered further subgroup analysis. Given PN’s pronounced sex and ethnicity skew, it is important to examine underrepresented groups to accurately assess their cardiovascular risk.
• In this propensity-score matched analysis, researchers identified 64,801 patients (59.44% women) with PN using electronic health reports from the Global Collaborative Network of TriNetX and matched to individuals without PN.
• Researchers calculated risks for 15 cardiovascular endpoints and all-cause mortality within 10 years of diagnosis. Major adverse cardiovascular events (MACE) included acute cerebral and myocardial infarction (MI), heart failure, ventricular arrhythmia, and sudden cardiac death.

TAKEAWAY:

• Patients with PN showed a higher risk for death (hazard ratio [HR], 1.1243) and MACE (HR, 1.117) (P < .0001 for both).
• PN was also associated with a higher risk for heart failure (HR, 1.062), thrombotic venous disease (HR, 1.26), angina pectoris (HR, 1.096), and peripheral arterial diseases (HR, 1.082) (P < .0001 for all) and for acute MI (HR, 1.11; P = .0015) and valve disorders (HR, 1.08; P = .0018).
• White patients with PN had a significantly increased risk for MACE, death, heart failure, cardiac arrest, vascular diseases, and acute MI, but this was not observed in people of color.
• Women exhibited a higher risk for MACE, heart failure, peripheral artery disease, acute MI, conduction disease, and valve disorders, while men did not have an increased risk for major or acute cardiovascular events. Both men and women had a higher risk for death, chronic ischemic heart disease, and venous disease.

IN PRACTICE:

“Although no novel PN-specific treatment rationale can be derived from the presented data, the potential risk of subsequent cardiovascular disease should be considered in the care of patients with PN, which includes screening and optimal management of other additional cardiovascular risk factors,” the authors wrote.

LIMITATIONS:

Retrospective observational design introduced inherent biases. Misdiagnosis or false coding in electronic health records could affect the data accuracy and ethnicity-specific analyses.

SOURCE:

This work, led by Henning Olbrich, from the Department of Dermatology, University of Lübeck, Germany, was published online in eBioMedicine.

DISCLOSURES:

The study was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft, and the State of Schleswig-Holstein. One author declared financial ties outside this work, and one author is an employee of TriNetX.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A large international cohort study identified a higher risk for cardiovascular diseases and mortality in patients with prurigo nodularis (PN), particularly among women and White patients.

METHODOLOGY:

• Studies have shown increased risks for cardiovascular diseases in patients with PN, but limited sample sizes have hindered further subgroup analysis. Given PN’s pronounced sex and ethnicity skew, it is important to examine underrepresented groups to accurately assess their cardiovascular risk.
• In this propensity-score matched analysis, researchers identified 64,801 patients (59.44% women) with PN using electronic health reports from the Global Collaborative Network of TriNetX and matched to individuals without PN.
• Researchers calculated risks for 15 cardiovascular endpoints and all-cause mortality within 10 years of diagnosis. Major adverse cardiovascular events (MACE) included acute cerebral and myocardial infarction (MI), heart failure, ventricular arrhythmia, and sudden cardiac death.

TAKEAWAY:

• Patients with PN showed a higher risk for death (hazard ratio [HR], 1.1243) and MACE (HR, 1.117) (P < .0001 for both).
• PN was also associated with a higher risk for heart failure (HR, 1.062), thrombotic venous disease (HR, 1.26), angina pectoris (HR, 1.096), and peripheral arterial diseases (HR, 1.082) (P < .0001 for all) and for acute MI (HR, 1.11; P = .0015) and valve disorders (HR, 1.08; P = .0018).
• White patients with PN had a significantly increased risk for MACE, death, heart failure, cardiac arrest, vascular diseases, and acute MI, but this was not observed in people of color.
• Women exhibited a higher risk for MACE, heart failure, peripheral artery disease, acute MI, conduction disease, and valve disorders, while men did not have an increased risk for major or acute cardiovascular events. Both men and women had a higher risk for death, chronic ischemic heart disease, and venous disease.

IN PRACTICE:

“Although no novel PN-specific treatment rationale can be derived from the presented data, the potential risk of subsequent cardiovascular disease should be considered in the care of patients with PN, which includes screening and optimal management of other additional cardiovascular risk factors,” the authors wrote.

LIMITATIONS:

Retrospective observational design introduced inherent biases. Misdiagnosis or false coding in electronic health records could affect the data accuracy and ethnicity-specific analyses.

SOURCE:

This work, led by Henning Olbrich, from the Department of Dermatology, University of Lübeck, Germany, was published online in eBioMedicine.

DISCLOSURES:

The study was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft, and the State of Schleswig-Holstein. One author declared financial ties outside this work, and one author is an employee of TriNetX.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A large international cohort study identified a higher risk for cardiovascular diseases and mortality in patients with prurigo nodularis (PN), particularly among women and White patients.

METHODOLOGY:

• Studies have shown increased risks for cardiovascular diseases in patients with PN, but limited sample sizes have hindered further subgroup analysis. Given PN’s pronounced sex and ethnicity skew, it is important to examine underrepresented groups to accurately assess their cardiovascular risk.
• In this propensity-score matched analysis, researchers identified 64,801 patients (59.44% women) with PN using electronic health reports from the Global Collaborative Network of TriNetX and matched to individuals without PN.
• Researchers calculated risks for 15 cardiovascular endpoints and all-cause mortality within 10 years of diagnosis. Major adverse cardiovascular events (MACE) included acute cerebral and myocardial infarction (MI), heart failure, ventricular arrhythmia, and sudden cardiac death.

TAKEAWAY:

• Patients with PN showed a higher risk for death (hazard ratio [HR], 1.1243) and MACE (HR, 1.117) (P < .0001 for both).
• PN was also associated with a higher risk for heart failure (HR, 1.062), thrombotic venous disease (HR, 1.26), angina pectoris (HR, 1.096), and peripheral arterial diseases (HR, 1.082) (P < .0001 for all) and for acute MI (HR, 1.11; P = .0015) and valve disorders (HR, 1.08; P = .0018).
• White patients with PN had a significantly increased risk for MACE, death, heart failure, cardiac arrest, vascular diseases, and acute MI, but this was not observed in people of color.
• Women exhibited a higher risk for MACE, heart failure, peripheral artery disease, acute MI, conduction disease, and valve disorders, while men did not have an increased risk for major or acute cardiovascular events. Both men and women had a higher risk for death, chronic ischemic heart disease, and venous disease.

IN PRACTICE:

“Although no novel PN-specific treatment rationale can be derived from the presented data, the potential risk of subsequent cardiovascular disease should be considered in the care of patients with PN, which includes screening and optimal management of other additional cardiovascular risk factors,” the authors wrote.

LIMITATIONS:

Retrospective observational design introduced inherent biases. Misdiagnosis or false coding in electronic health records could affect the data accuracy and ethnicity-specific analyses.

SOURCE:

This work, led by Henning Olbrich, from the Department of Dermatology, University of Lübeck, Germany, was published online in eBioMedicine.

DISCLOSURES:

The study was supported by the University of Lübeck, the Deutsche Forschungsgemeinschaft, and the State of Schleswig-Holstein. One author declared financial ties outside this work, and one author is an employee of TriNetX.
 

A version of this article appeared on Medscape.com.

As three federal agencies investigate how private equity ownership and consolidation of healthcare organizations affects patient care and costs, physicians are giving them an earful.

“Before I retired, I could already see the damage private equity was doing to hospitals and medical practices. Well-regarded physician groups were being bought and the respected doctors and staff forced out to squeeze out profit for the buyers. Hospital-based physicians were being hit especially hard,” wrote Rhonda Wright, MD, of Brookhaven, Georgia. 

“Now, the rot is setting in for emergency rooms. One in four ERs is now (under-)staffed by private equity firms. This is leading to longer wait times, deterioration in patient care, and higher bills,” Dr. Wright continued. “Private equity takeover of medicine must be stopped. All such deals should be strictly regulated and should be heavily scrutinized, if not barred altogether. Our health depends upon it!”

The federal government is accepting public comments like Dr. Wright’s through June 5 and has even set up a website (healthycompetition.gov) to make it easier to file complaints against health organizations possibly violating antitrust laws.

The US Department of Justice’s Antitrust Division, the Federal Trade Commission (FTC), and the Department of Health and Human Services want to hear from physicians and the public about how private equity firms’ investments in healthcare entities, such as hospitals, nursing homes, or specialty service providers, affect patients and healthcare workers. The investigation will also evaluate how market pricing, competition, and referral patterns change when practices and hospitals are acquired by health systems or insurers.

Maintaining competition in the provider and payer markets benefits healthcare workers through higher pay, while patients can access quality care at lower prices, the joint request for information said. However, consolidation and mergers — potentially driven by private equity’s entry into the market — can diminish these benefits.

Investigating private equity and consolidation in medicine is part of the Biden Administration’s focus on lowering medical and prescription drug costs and strengthening competition in healthcare. The FTC’s vote last week to ban noncompete agreements, which business groups have vowed to challenge in court, falls under the same initiative.

Alexandra Nicole Thran, MD, FACEP, president of the Vermont Chapter of the American College of Emergency Physicians, said that the private equity business model is problematic because it ties physicians’ wages to patient satisfaction and the number of patients they see per hour. 

A Connecticut primary care physician expressed similar sentiments. “Physicians are being forced into a system where corporations provide financial incentives and punitive policies to direct healthcare decisions towards a profitable aim,” said Eric Schwaber, MD. 

While a majority of comments criticized the role of private equity and consolidation, some reflected a more positive view. 

“Private equity helps make healthcare more efficient and effective. It brings needed operational and managerial expertise to allow for better patient care,” said Reenie Abraham, MD, an associate professor in the Department of Internal Medicine at University of Texas Southwestern Medical Center, Dallas. The University of Texas is facing a lawsuit involving the liability status of its physicians who work for a private equity-backed hospital partly owned by the university.

Several public comments point to the increasing market influence UnitedHealth Group (UHG) and other payers have obtained through recent acquisitions. Retired emergency room physician Scott Davis, MD, said that the “astronomical” rate of burnout among providers has been exacerbated by “the economic takeover of the healthcare system by…United Healthcare [and] private equity groups who put profits over anything else.”  

The healthcare conglomerate employs approximately 10% of active US physicians, including many through its subsidiary, Optum Health, which provides primary, urgent, and surgical care. UHG has also invested heavily in acquiring physician practices to advance its value-based care model.

“If a publicly traded private insurance or private equity company is interested in their short-term quarterly profits or stock price, there is little interest in the…effective management of chronic disease, other than that which fulfills a ‘value-based’ metric,” wrote Kenneth Dolkart, MD, FACP, clinical assistant professor at the Dartmouth Geisel School of Medicine in Hanover, New Hampshire. 

Sarah Ealy, a revenue cycle professional, commented that payers like UHG have outsized bargaining power when negotiating rates with providers. “In many states, United Healthcare and its subsidiaries pay a lower reimbursement rate than state Medicaid plans — these rates are nearly 50% of the breakeven per-visit rate that practices need to keep the lights on.”

Another comment ties the recent cyberattack on UHG-owned Change Healthcare to private equity ownership and “healthcare behemoths buying up practices and data.”

“The ramrodding of consolidation and private oversight with little to no barriers to foreign intrusions…is a testament to how ill prepared [the] US market is to private equity healthcare takeovers,” said SW Dermatology Practice LLC. 

The agencies request comments from all health market participants, including physicians, nurses, employers, administrators, and patients.

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

As three federal agencies investigate how private equity ownership and consolidation of healthcare organizations affects patient care and costs, physicians are giving them an earful.

“Before I retired, I could already see the damage private equity was doing to hospitals and medical practices. Well-regarded physician groups were being bought and the respected doctors and staff forced out to squeeze out profit for the buyers. Hospital-based physicians were being hit especially hard,” wrote Rhonda Wright, MD, of Brookhaven, Georgia. 

“Now, the rot is setting in for emergency rooms. One in four ERs is now (under-)staffed by private equity firms. This is leading to longer wait times, deterioration in patient care, and higher bills,” Dr. Wright continued. “Private equity takeover of medicine must be stopped. All such deals should be strictly regulated and should be heavily scrutinized, if not barred altogether. Our health depends upon it!”

The federal government is accepting public comments like Dr. Wright’s through June 5 and has even set up a website (healthycompetition.gov) to make it easier to file complaints against health organizations possibly violating antitrust laws.

The US Department of Justice’s Antitrust Division, the Federal Trade Commission (FTC), and the Department of Health and Human Services want to hear from physicians and the public about how private equity firms’ investments in healthcare entities, such as hospitals, nursing homes, or specialty service providers, affect patients and healthcare workers. The investigation will also evaluate how market pricing, competition, and referral patterns change when practices and hospitals are acquired by health systems or insurers.

Maintaining competition in the provider and payer markets benefits healthcare workers through higher pay, while patients can access quality care at lower prices, the joint request for information said. However, consolidation and mergers — potentially driven by private equity’s entry into the market — can diminish these benefits.

Investigating private equity and consolidation in medicine is part of the Biden Administration’s focus on lowering medical and prescription drug costs and strengthening competition in healthcare. The FTC’s vote last week to ban noncompete agreements, which business groups have vowed to challenge in court, falls under the same initiative.

Alexandra Nicole Thran, MD, FACEP, president of the Vermont Chapter of the American College of Emergency Physicians, said that the private equity business model is problematic because it ties physicians’ wages to patient satisfaction and the number of patients they see per hour. 

A Connecticut primary care physician expressed similar sentiments. “Physicians are being forced into a system where corporations provide financial incentives and punitive policies to direct healthcare decisions towards a profitable aim,” said Eric Schwaber, MD. 

While a majority of comments criticized the role of private equity and consolidation, some reflected a more positive view. 

“Private equity helps make healthcare more efficient and effective. It brings needed operational and managerial expertise to allow for better patient care,” said Reenie Abraham, MD, an associate professor in the Department of Internal Medicine at University of Texas Southwestern Medical Center, Dallas. The University of Texas is facing a lawsuit involving the liability status of its physicians who work for a private equity-backed hospital partly owned by the university.

Several public comments point to the increasing market influence UnitedHealth Group (UHG) and other payers have obtained through recent acquisitions. Retired emergency room physician Scott Davis, MD, said that the “astronomical” rate of burnout among providers has been exacerbated by “the economic takeover of the healthcare system by…United Healthcare [and] private equity groups who put profits over anything else.”  

The healthcare conglomerate employs approximately 10% of active US physicians, including many through its subsidiary, Optum Health, which provides primary, urgent, and surgical care. UHG has also invested heavily in acquiring physician practices to advance its value-based care model.

“If a publicly traded private insurance or private equity company is interested in their short-term quarterly profits or stock price, there is little interest in the…effective management of chronic disease, other than that which fulfills a ‘value-based’ metric,” wrote Kenneth Dolkart, MD, FACP, clinical assistant professor at the Dartmouth Geisel School of Medicine in Hanover, New Hampshire. 

Sarah Ealy, a revenue cycle professional, commented that payers like UHG have outsized bargaining power when negotiating rates with providers. “In many states, United Healthcare and its subsidiaries pay a lower reimbursement rate than state Medicaid plans — these rates are nearly 50% of the breakeven per-visit rate that practices need to keep the lights on.”

Another comment ties the recent cyberattack on UHG-owned Change Healthcare to private equity ownership and “healthcare behemoths buying up practices and data.”

“The ramrodding of consolidation and private oversight with little to no barriers to foreign intrusions…is a testament to how ill prepared [the] US market is to private equity healthcare takeovers,” said SW Dermatology Practice LLC. 

The agencies request comments from all health market participants, including physicians, nurses, employers, administrators, and patients.

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

As three federal agencies investigate how private equity ownership and consolidation of healthcare organizations affects patient care and costs, physicians are giving them an earful.

“Before I retired, I could already see the damage private equity was doing to hospitals and medical practices. Well-regarded physician groups were being bought and the respected doctors and staff forced out to squeeze out profit for the buyers. Hospital-based physicians were being hit especially hard,” wrote Rhonda Wright, MD, of Brookhaven, Georgia. 

“Now, the rot is setting in for emergency rooms. One in four ERs is now (under-)staffed by private equity firms. This is leading to longer wait times, deterioration in patient care, and higher bills,” Dr. Wright continued. “Private equity takeover of medicine must be stopped. All such deals should be strictly regulated and should be heavily scrutinized, if not barred altogether. Our health depends upon it!”

The federal government is accepting public comments like Dr. Wright’s through June 5 and has even set up a website (healthycompetition.gov) to make it easier to file complaints against health organizations possibly violating antitrust laws.

The US Department of Justice’s Antitrust Division, the Federal Trade Commission (FTC), and the Department of Health and Human Services want to hear from physicians and the public about how private equity firms’ investments in healthcare entities, such as hospitals, nursing homes, or specialty service providers, affect patients and healthcare workers. The investigation will also evaluate how market pricing, competition, and referral patterns change when practices and hospitals are acquired by health systems or insurers.

Maintaining competition in the provider and payer markets benefits healthcare workers through higher pay, while patients can access quality care at lower prices, the joint request for information said. However, consolidation and mergers — potentially driven by private equity’s entry into the market — can diminish these benefits.

Investigating private equity and consolidation in medicine is part of the Biden Administration’s focus on lowering medical and prescription drug costs and strengthening competition in healthcare. The FTC’s vote last week to ban noncompete agreements, which business groups have vowed to challenge in court, falls under the same initiative.

Alexandra Nicole Thran, MD, FACEP, president of the Vermont Chapter of the American College of Emergency Physicians, said that the private equity business model is problematic because it ties physicians’ wages to patient satisfaction and the number of patients they see per hour. 

A Connecticut primary care physician expressed similar sentiments. “Physicians are being forced into a system where corporations provide financial incentives and punitive policies to direct healthcare decisions towards a profitable aim,” said Eric Schwaber, MD. 

While a majority of comments criticized the role of private equity and consolidation, some reflected a more positive view. 

“Private equity helps make healthcare more efficient and effective. It brings needed operational and managerial expertise to allow for better patient care,” said Reenie Abraham, MD, an associate professor in the Department of Internal Medicine at University of Texas Southwestern Medical Center, Dallas. The University of Texas is facing a lawsuit involving the liability status of its physicians who work for a private equity-backed hospital partly owned by the university.

Several public comments point to the increasing market influence UnitedHealth Group (UHG) and other payers have obtained through recent acquisitions. Retired emergency room physician Scott Davis, MD, said that the “astronomical” rate of burnout among providers has been exacerbated by “the economic takeover of the healthcare system by…United Healthcare [and] private equity groups who put profits over anything else.”  

The healthcare conglomerate employs approximately 10% of active US physicians, including many through its subsidiary, Optum Health, which provides primary, urgent, and surgical care. UHG has also invested heavily in acquiring physician practices to advance its value-based care model.

“If a publicly traded private insurance or private equity company is interested in their short-term quarterly profits or stock price, there is little interest in the…effective management of chronic disease, other than that which fulfills a ‘value-based’ metric,” wrote Kenneth Dolkart, MD, FACP, clinical assistant professor at the Dartmouth Geisel School of Medicine in Hanover, New Hampshire. 

Sarah Ealy, a revenue cycle professional, commented that payers like UHG have outsized bargaining power when negotiating rates with providers. “In many states, United Healthcare and its subsidiaries pay a lower reimbursement rate than state Medicaid plans — these rates are nearly 50% of the breakeven per-visit rate that practices need to keep the lights on.”

Another comment ties the recent cyberattack on UHG-owned Change Healthcare to private equity ownership and “healthcare behemoths buying up practices and data.”

“The ramrodding of consolidation and private oversight with little to no barriers to foreign intrusions…is a testament to how ill prepared [the] US market is to private equity healthcare takeovers,” said SW Dermatology Practice LLC. 

The agencies request comments from all health market participants, including physicians, nurses, employers, administrators, and patients.

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

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

Pharmaceutical giant Eli Lilly recently announced that its newly approved weight loss medication Zepbound — a glucagon-like peptide 1 receptor agonist (GLP-1 RA) akin to Mounjaro, Ozempic, and Wegovy — will be prescribed by independent telehealth providers on a platform managed by the company itself. The drug can be subsequently shipped direct to consumer (DTC), allowing delivery straight to patients’ homes. 

This arrangement raises serious concerns about an inherent conflict of interest, as we previously discussed. What happens when a pharmaceutical company influences access to remote providers who prescribe the very medications it manufactures? Will these remote providers truly put the patient’s interest first when debating their safety and appropriate use? Whom will patients consult if they have concerns after initiating the medication?

Without new guardrails, the potential for misleading messaging to result in dangerous prescribing patterns looms large. The United States is one of only two countries to allow DTC advertising of prescription drugs, and the explosion in demand for GLP-1 RAs is partly attributable to this model (Oh, oh, Ozempic, anyone?). Americans spent over $78 billion on weight loss goods and services in 2019; time-intensive approaches such as diet and exercise are understandably difficult, and the public has always looked for a magic cure. Although GLP-1 RAs are promising, they may present a path to disaster without proper supervision.

LillyDirect, which in addition to Zepbound offers migraine medications and other products in the company’s catalogue, primarily aims to increase access to medication and reduce costs of the drugs for consumers. The stated mission is noble: By cutting out the middlemen of traditional pharmacies and benefit managers, administrative costs drop. LillyDirect goes a step further by reducing the need for patients to visit their regular family doctor to receive these medications.

On the surface, this design appears promising. Wait times for doctor’s appointments will fall. Patients can order drugs from the comfort of their home. Everyone benefits. Or do they? 

Although easier access and reduced cost may be an apparent win for patients, DTC arrangements complicate the ethics of prescriptions and patient follow-up. This model reminds us of the roots of the opioid crisis, where powerful advertising and relationships between prescribers and drugmakers led to great harm. Providers often faced a conflict of interest when prescribing dangerous drugs to patients who requested them. We must learn from these mistakes to ensure there is critical oversight into the independence of prescribers used by LillyDirect and other DTC platforms.

Adding to these parallels, once a patient begins a GLP-1 medication such as Zepbound, stopping treatment will probably lead to regaining lost weight, serving as negative reinforcement. Hence, patients may decide never to discontinue these medications.

Obtaining what amounts to a lifelong prescription from a telehealth provider who may never follow a patient sets a dangerous precedent that will be difficult to unravel once begun. Recent challenges in access to medications such as Zepbound have been complicated by supply chain and manufacturing issues, leading to potential interruptions in patient access, ultimately affecting compliance. The rapid increase in online providers indicates competition for distribution channels has sharply increased and poses a threat to Lilly’s DTC site. 

Furthermore, the lack of a regular physician to monitor patients introduces uncertainty in safety and continuity of care. These are important tenets in protecting patients, especially patients who are not diabetic and desire a quick fix. We have already seen a huge, arguably unrestrained, rise in prescriptions of GLP-1 RAs for weight loss — up to a 352% increase in 2023.

These drugs have shown great promise and are generally safe when used in the right patient, but important contraindications exist — namely, serious gastrointestinal side effects and low blood glucose in nondiabetic persons — that an astute physician must consider. Patients desiring these medications often must undergo comprehensive laboratory testing and cardiac evaluation, both before initiation and during regular follow-up, to check for comorbidities.

The American College of Physicians cautioned against such prescribing practices in a recent position statement, emphasizing that the lack of an established care provider could adversely affect patients. We note that the potential harms of DTC sales would concentrate in economically and racially underserved communities, where obesity, lack of insurance, and low health literacy are more common. 

But the DTC genie is out of the pill bottle, and as such platforms become more common, patients will inherently take more ownership over their medical care. Remote providers will of course not be following these patients and evaluating for side effects. As a result, we in medical practice must be abreast of new downsides of these medications if and when they arise. 

Every clinician must be aware of the medications a patient is taking, even those that they did not prescribe. They should educate their patients about drug-drug interactions and side effects and order lab tests to monitor for side effects. 

Independent physicians abide by an underlying oath: First, do no harm. They serve as a trusted check on industry and a valuable long-term partner for patients. Where are the guardrails to protect patients and ensure that pharmaceutical companies are not essentially pushing prescriptions for their own products? Will traditional healthcare providers be effectively relegated to a bystander role in Lilly’s transactional approach to medication distribution? Unlike other commercial goods, pharmacologics have great nuance; not every approved medication is meant for every patient.

A version of this article appeared on Medscape.com.

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

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

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

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

The Inflammatory Pathway

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

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

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

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

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

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

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

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

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

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

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

Slow to Embrace Colchicine

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

NYU Langone

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

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

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

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

A version of this article appeared on Medscape.com .

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

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

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

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

The Inflammatory Pathway

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

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

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

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

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

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

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

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

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

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

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

Slow to Embrace Colchicine

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

NYU Langone

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

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

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

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

A version of this article appeared on Medscape.com .

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

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

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

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

The Inflammatory Pathway

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

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

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

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

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

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

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

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

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

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

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

Slow to Embrace Colchicine

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

NYU Langone

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

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

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

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

A version of this article appeared on Medscape.com .

Amyloidosis is a condition marked by the accumulation of insoluble beta-sheet fibrillar protein aggregates in tissues that can be acquired or hereditary. Hereditary amyloidogenic transthyretin (hATTR) amyloidosis is an autosomal-dominant disease caused by pathogenic variants in the TTR gene. The TTR protein is essential for transporting thyroxine and retinol-binding protein and is primarily synthesized in the liver, becoming unstable as a result of the pathogenic mutations. Inherited pathogenic variants lead to the protein’s misfolding, aggregation, and deposition as amyloid fibrils in different organs, resulting in progressive multisystem dysfunction. hATTR amyloidosis is a heterogenous disease, characterized by a wide range of clinical manifestations affecting the peripheral (both somatic and autonomic) nervous system, heart, kidneys, and central nervous system (CNS); however, the heart and peripheral nerves appear to be the main targets of the TTR-related pathologic process. Without treatment, the prognosis is poor, with an average life expectancy of 7-11 years; however, in recent years, the development of new therapeutics has brought new hope to patients.

Here are five things to know about hereditary amyloidosis.
 

1. Diagnosis of hereditary amyloidosis requires a high level of suspicion.

The diagnosis of hATTR amyloidosis presents a significant challenge, particularly in nonendemic regions where a lack of family history and heterogeneity of clinical presentation can delay diagnosis by 4-5 years. A timely diagnosis requires clinicians to maintain a high index of suspicion, especially when evaluating patients with neuropathic symptoms. Early diagnosis is crucial to begin patients on recently available disease-modifying therapies that can slow the disease course. Failure to recognize is the major barrier to improved patient outcomes.

Confirming the diagnosis involves detecting amyloid deposits in tissue biopsy specimens from various possible sites, including the skin, nerves, myocardium, and others. However, the diagnosis can be challenging owing to the uneven distribution of amyloid fibrils, sometimes requiring multiple biopsies or alternative diagnostic approaches, such as TTR gene sequencing, to confirm the presence of an amyloidogenic pathogenic variant. Biopsy for hATTR amyloidosis is not required if imaging of the clinical phenotype and genetic testing are consistent.

Once diagnosed, the assessment of organ involvement is essential, using nerve conduction studies, cardiac investigations (eg, echocardiography, ECG, scintigraphy), ophthalmologic assessments, and complete renal function evaluations to fully understand the extent of disease impact.
 

2. Hereditary amyloidosis diseases are classified into two primary categories.

Hereditary amyloidosis represents a group of diseases caused by inherited gene mutations and is classified into two main types: ATTR (transthyretin-related) and non-TTR. Most cases of hereditary amyloidosis are associated with the TTR gene. Mutations in this protein lead to different forms of ATTR amyloidosis, categorized on the basis of the specific mutation involved, such as hATTR50M (genotype Val50Met), which is the most prevalent form.

ATTR mutations result in a variety of health issues, manifesting in three primary forms:

• Neuropathic ATTR (genotype Val50Met): Early symptoms include sensorimotor polyneuropathy of the legs, carpal tunnel syndrome, autonomic dysfunction, constipation/diarrhea, and impotence; late symptoms include cardiomyopathy, vitreous opacities, glaucoma, nephropathy, and CNS symptoms.
• Cardiac ATTR (genotype Val142Ile): This type is characterized by cardiomegaly, conduction block, arrhythmia, anginal pain, congestive heart failure, and sudden death.
• Leptomeningeal ATTR (genotype Asp38Gly): This is characterized by transient focal neurologic episodes, intracerebral and/or subarachnoid hemorrhages, dementia, ataxia, and psychosis.

Non-TTR amyloidoses are rarer than are ATTR variations and involve mutations in different genes that also have significant health impacts. These include proteins such as apolipoprotein AI, fibrinogen A alpha, lysozyme, apolipoprotein AII, gelsolin, and cystatin C. Each type contributes to a range of symptoms and requires individualized management approaches.
 

3. Heightened disease awareness has increased the recognized prevalence of hereditary amyloidosis.

hATTR amyloidosis has historically been recognized as a rare disease, with significant clusters in Portugal, Brazil, Sweden, and Japan and alongside smaller foci in regions such as Cyprus and Majorca. This disease›s variable incidence across Europe is now perceived to be on the rise. It is attributed to heightened disease awareness among healthcare providers and the broader availability of genetic testing, extending its recognized impact to at least 29 countries globally. The genetic landscape of hATTR amyloidosis is diverse, with over 140 mutations identified in the TTR gene. Among these, the Val50Met mutation is particularly notable for its association with large patient clusters in the endemic regions.

Morbidity and mortality associated with hATTR amyloidosis are significant, with an average lifespan of 7-11 years post diagnosis; however, survival rates can vary widely depending on the specific genetic variant and organ involvement. Early diagnosis can substantially improve outcomes; yet, for many, the prognosis remains poor, especially in cases dominated by cardiomyopathy. Genetics play a central role in the disease›s transmission, with autosomal-dominant inheritance patterns and high penetrance among carriers of pathogenic mutations. Research continues to uncover the broad spectrum of genetic variations contributing to hATTR amyloidosis, with ongoing studies poised to expand our understanding of its molecular underpinnings and potential treatment options.

4. The effect on quality of life is significant both in patients living with hATTR amyloidosis and their caregivers.

hATTR amyloidosis imposes a multifaceted burden on patients and their caregivers as the disease progresses. Symptoms range from sensorimotor impairment and gastrointestinal or autonomic dysfunction to heart failure, leading to significant health-related quality-of-life deficits. The systemic nature of hATTR amyloidosis significantly affects patients› lifestyles, daily activities, and general well-being, especially because it typically manifests in adulthood — a crucial time for occupational changes. The progression of hATTR amyloidosis exacerbates the challenges in maintaining employment and managing household chores, with symptomatic patients often unable to work and experiencing difficulties with absenteeism and presenteeism when they are able to work.

hATTR amyloidosis leads to physical, mental, occupational, and social limitations for patients, and it also places a considerable strain on their families and caregivers, who report poor mental health, work impairment, and a high time commitment (mean, 45.9 h/wk) to providing care.

5. There have been significant advancements in therapeutic options for early-stage hATTR amyloidosis.

After diagnosis, prompt initiation of treatment is recommended to delay the progression of hATTR amyloidosis; a multidisciplinary approach is essential, incorporating anti-amyloid therapy to inhibit further production and/or deposition of amyloid aggregates. Treatment strategies also include addressing symptomatic therapy and managing cardiac, renal, and ocular involvement. Although many therapies have been developed, especially for the early stages of hATTR amyloidosis, therapeutic benefits for patients with advanced disease remain limited.

Recent advancements in the treatment of hATTR amyloidosis have introduced RNA-targeted therapies including patisiran, vutrisiran, and eplontersen, which have shown efficacy in reducing hepatic TTR synthesis and the aggregation of misfolded monomers into amyloid deposits. These therapies, ranging from small interfering RNA formulations to antisense oligonucleotides, offer benefits in managing both cardiomyopathy and neuropathy associated with hATTR amyloidosis , administered through various methods, including intravenous infusions and subcutaneous injections. In addition, the stabilization of TTR tetramers with the use of drugs such as tafamidis and diflunisal has effectively prevented the formation of amyloidogenic monomers. Moreover, other investigational agents, including TTR stabilizers like acoramidis and tolcapone, as well as novel compounds that inhibit amyloid formation and disrupt fibrils, are expanding the therapeutic landscape for hATTR amyloidosis , providing hope for improved management of this complex condition.

Dr. Gertz is a professor and consultant in the Department of Hematology, Mayo Clinic, Rochester, Minnesota. He has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from AstraZeneca, Ionis, and Alnylym.

A version of this article appeared on Medscape.com.

Amyloidosis is a condition marked by the accumulation of insoluble beta-sheet fibrillar protein aggregates in tissues that can be acquired or hereditary. Hereditary amyloidogenic transthyretin (hATTR) amyloidosis is an autosomal-dominant disease caused by pathogenic variants in the TTR gene. The TTR protein is essential for transporting thyroxine and retinol-binding protein and is primarily synthesized in the liver, becoming unstable as a result of the pathogenic mutations. Inherited pathogenic variants lead to the protein’s misfolding, aggregation, and deposition as amyloid fibrils in different organs, resulting in progressive multisystem dysfunction. hATTR amyloidosis is a heterogenous disease, characterized by a wide range of clinical manifestations affecting the peripheral (both somatic and autonomic) nervous system, heart, kidneys, and central nervous system (CNS); however, the heart and peripheral nerves appear to be the main targets of the TTR-related pathologic process. Without treatment, the prognosis is poor, with an average life expectancy of 7-11 years; however, in recent years, the development of new therapeutics has brought new hope to patients.

Here are five things to know about hereditary amyloidosis.
 

1. Diagnosis of hereditary amyloidosis requires a high level of suspicion.

The diagnosis of hATTR amyloidosis presents a significant challenge, particularly in nonendemic regions where a lack of family history and heterogeneity of clinical presentation can delay diagnosis by 4-5 years. A timely diagnosis requires clinicians to maintain a high index of suspicion, especially when evaluating patients with neuropathic symptoms. Early diagnosis is crucial to begin patients on recently available disease-modifying therapies that can slow the disease course. Failure to recognize is the major barrier to improved patient outcomes.

Confirming the diagnosis involves detecting amyloid deposits in tissue biopsy specimens from various possible sites, including the skin, nerves, myocardium, and others. However, the diagnosis can be challenging owing to the uneven distribution of amyloid fibrils, sometimes requiring multiple biopsies or alternative diagnostic approaches, such as TTR gene sequencing, to confirm the presence of an amyloidogenic pathogenic variant. Biopsy for hATTR amyloidosis is not required if imaging of the clinical phenotype and genetic testing are consistent.

Once diagnosed, the assessment of organ involvement is essential, using nerve conduction studies, cardiac investigations (eg, echocardiography, ECG, scintigraphy), ophthalmologic assessments, and complete renal function evaluations to fully understand the extent of disease impact.
 

2. Hereditary amyloidosis diseases are classified into two primary categories.

Hereditary amyloidosis represents a group of diseases caused by inherited gene mutations and is classified into two main types: ATTR (transthyretin-related) and non-TTR. Most cases of hereditary amyloidosis are associated with the TTR gene. Mutations in this protein lead to different forms of ATTR amyloidosis, categorized on the basis of the specific mutation involved, such as hATTR50M (genotype Val50Met), which is the most prevalent form.

ATTR mutations result in a variety of health issues, manifesting in three primary forms:

• Neuropathic ATTR (genotype Val50Met): Early symptoms include sensorimotor polyneuropathy of the legs, carpal tunnel syndrome, autonomic dysfunction, constipation/diarrhea, and impotence; late symptoms include cardiomyopathy, vitreous opacities, glaucoma, nephropathy, and CNS symptoms.
• Cardiac ATTR (genotype Val142Ile): This type is characterized by cardiomegaly, conduction block, arrhythmia, anginal pain, congestive heart failure, and sudden death.
• Leptomeningeal ATTR (genotype Asp38Gly): This is characterized by transient focal neurologic episodes, intracerebral and/or subarachnoid hemorrhages, dementia, ataxia, and psychosis.

Non-TTR amyloidoses are rarer than are ATTR variations and involve mutations in different genes that also have significant health impacts. These include proteins such as apolipoprotein AI, fibrinogen A alpha, lysozyme, apolipoprotein AII, gelsolin, and cystatin C. Each type contributes to a range of symptoms and requires individualized management approaches.
 

3. Heightened disease awareness has increased the recognized prevalence of hereditary amyloidosis.

hATTR amyloidosis has historically been recognized as a rare disease, with significant clusters in Portugal, Brazil, Sweden, and Japan and alongside smaller foci in regions such as Cyprus and Majorca. This disease›s variable incidence across Europe is now perceived to be on the rise. It is attributed to heightened disease awareness among healthcare providers and the broader availability of genetic testing, extending its recognized impact to at least 29 countries globally. The genetic landscape of hATTR amyloidosis is diverse, with over 140 mutations identified in the TTR gene. Among these, the Val50Met mutation is particularly notable for its association with large patient clusters in the endemic regions.

Morbidity and mortality associated with hATTR amyloidosis are significant, with an average lifespan of 7-11 years post diagnosis; however, survival rates can vary widely depending on the specific genetic variant and organ involvement. Early diagnosis can substantially improve outcomes; yet, for many, the prognosis remains poor, especially in cases dominated by cardiomyopathy. Genetics play a central role in the disease›s transmission, with autosomal-dominant inheritance patterns and high penetrance among carriers of pathogenic mutations. Research continues to uncover the broad spectrum of genetic variations contributing to hATTR amyloidosis, with ongoing studies poised to expand our understanding of its molecular underpinnings and potential treatment options.

4. The effect on quality of life is significant both in patients living with hATTR amyloidosis and their caregivers.

hATTR amyloidosis imposes a multifaceted burden on patients and their caregivers as the disease progresses. Symptoms range from sensorimotor impairment and gastrointestinal or autonomic dysfunction to heart failure, leading to significant health-related quality-of-life deficits. The systemic nature of hATTR amyloidosis significantly affects patients› lifestyles, daily activities, and general well-being, especially because it typically manifests in adulthood — a crucial time for occupational changes. The progression of hATTR amyloidosis exacerbates the challenges in maintaining employment and managing household chores, with symptomatic patients often unable to work and experiencing difficulties with absenteeism and presenteeism when they are able to work.

hATTR amyloidosis leads to physical, mental, occupational, and social limitations for patients, and it also places a considerable strain on their families and caregivers, who report poor mental health, work impairment, and a high time commitment (mean, 45.9 h/wk) to providing care.

5. There have been significant advancements in therapeutic options for early-stage hATTR amyloidosis.

After diagnosis, prompt initiation of treatment is recommended to delay the progression of hATTR amyloidosis; a multidisciplinary approach is essential, incorporating anti-amyloid therapy to inhibit further production and/or deposition of amyloid aggregates. Treatment strategies also include addressing symptomatic therapy and managing cardiac, renal, and ocular involvement. Although many therapies have been developed, especially for the early stages of hATTR amyloidosis, therapeutic benefits for patients with advanced disease remain limited.

Recent advancements in the treatment of hATTR amyloidosis have introduced RNA-targeted therapies including patisiran, vutrisiran, and eplontersen, which have shown efficacy in reducing hepatic TTR synthesis and the aggregation of misfolded monomers into amyloid deposits. These therapies, ranging from small interfering RNA formulations to antisense oligonucleotides, offer benefits in managing both cardiomyopathy and neuropathy associated with hATTR amyloidosis , administered through various methods, including intravenous infusions and subcutaneous injections. In addition, the stabilization of TTR tetramers with the use of drugs such as tafamidis and diflunisal has effectively prevented the formation of amyloidogenic monomers. Moreover, other investigational agents, including TTR stabilizers like acoramidis and tolcapone, as well as novel compounds that inhibit amyloid formation and disrupt fibrils, are expanding the therapeutic landscape for hATTR amyloidosis , providing hope for improved management of this complex condition.

Dr. Gertz is a professor and consultant in the Department of Hematology, Mayo Clinic, Rochester, Minnesota. He has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from AstraZeneca, Ionis, and Alnylym.

A version of this article appeared on Medscape.com.

Amyloidosis is a condition marked by the accumulation of insoluble beta-sheet fibrillar protein aggregates in tissues that can be acquired or hereditary. Hereditary amyloidogenic transthyretin (hATTR) amyloidosis is an autosomal-dominant disease caused by pathogenic variants in the TTR gene. The TTR protein is essential for transporting thyroxine and retinol-binding protein and is primarily synthesized in the liver, becoming unstable as a result of the pathogenic mutations. Inherited pathogenic variants lead to the protein’s misfolding, aggregation, and deposition as amyloid fibrils in different organs, resulting in progressive multisystem dysfunction. hATTR amyloidosis is a heterogenous disease, characterized by a wide range of clinical manifestations affecting the peripheral (both somatic and autonomic) nervous system, heart, kidneys, and central nervous system (CNS); however, the heart and peripheral nerves appear to be the main targets of the TTR-related pathologic process. Without treatment, the prognosis is poor, with an average life expectancy of 7-11 years; however, in recent years, the development of new therapeutics has brought new hope to patients.

Here are five things to know about hereditary amyloidosis.
 

1. Diagnosis of hereditary amyloidosis requires a high level of suspicion.

The diagnosis of hATTR amyloidosis presents a significant challenge, particularly in nonendemic regions where a lack of family history and heterogeneity of clinical presentation can delay diagnosis by 4-5 years. A timely diagnosis requires clinicians to maintain a high index of suspicion, especially when evaluating patients with neuropathic symptoms. Early diagnosis is crucial to begin patients on recently available disease-modifying therapies that can slow the disease course. Failure to recognize is the major barrier to improved patient outcomes.

Confirming the diagnosis involves detecting amyloid deposits in tissue biopsy specimens from various possible sites, including the skin, nerves, myocardium, and others. However, the diagnosis can be challenging owing to the uneven distribution of amyloid fibrils, sometimes requiring multiple biopsies or alternative diagnostic approaches, such as TTR gene sequencing, to confirm the presence of an amyloidogenic pathogenic variant. Biopsy for hATTR amyloidosis is not required if imaging of the clinical phenotype and genetic testing are consistent.

Once diagnosed, the assessment of organ involvement is essential, using nerve conduction studies, cardiac investigations (eg, echocardiography, ECG, scintigraphy), ophthalmologic assessments, and complete renal function evaluations to fully understand the extent of disease impact.
 

2. Hereditary amyloidosis diseases are classified into two primary categories.

Hereditary amyloidosis represents a group of diseases caused by inherited gene mutations and is classified into two main types: ATTR (transthyretin-related) and non-TTR. Most cases of hereditary amyloidosis are associated with the TTR gene. Mutations in this protein lead to different forms of ATTR amyloidosis, categorized on the basis of the specific mutation involved, such as hATTR50M (genotype Val50Met), which is the most prevalent form.

ATTR mutations result in a variety of health issues, manifesting in three primary forms:

• Neuropathic ATTR (genotype Val50Met): Early symptoms include sensorimotor polyneuropathy of the legs, carpal tunnel syndrome, autonomic dysfunction, constipation/diarrhea, and impotence; late symptoms include cardiomyopathy, vitreous opacities, glaucoma, nephropathy, and CNS symptoms.
• Cardiac ATTR (genotype Val142Ile): This type is characterized by cardiomegaly, conduction block, arrhythmia, anginal pain, congestive heart failure, and sudden death.
• Leptomeningeal ATTR (genotype Asp38Gly): This is characterized by transient focal neurologic episodes, intracerebral and/or subarachnoid hemorrhages, dementia, ataxia, and psychosis.

Non-TTR amyloidoses are rarer than are ATTR variations and involve mutations in different genes that also have significant health impacts. These include proteins such as apolipoprotein AI, fibrinogen A alpha, lysozyme, apolipoprotein AII, gelsolin, and cystatin C. Each type contributes to a range of symptoms and requires individualized management approaches.
 

3. Heightened disease awareness has increased the recognized prevalence of hereditary amyloidosis.

hATTR amyloidosis has historically been recognized as a rare disease, with significant clusters in Portugal, Brazil, Sweden, and Japan and alongside smaller foci in regions such as Cyprus and Majorca. This disease›s variable incidence across Europe is now perceived to be on the rise. It is attributed to heightened disease awareness among healthcare providers and the broader availability of genetic testing, extending its recognized impact to at least 29 countries globally. The genetic landscape of hATTR amyloidosis is diverse, with over 140 mutations identified in the TTR gene. Among these, the Val50Met mutation is particularly notable for its association with large patient clusters in the endemic regions.

Morbidity and mortality associated with hATTR amyloidosis are significant, with an average lifespan of 7-11 years post diagnosis; however, survival rates can vary widely depending on the specific genetic variant and organ involvement. Early diagnosis can substantially improve outcomes; yet, for many, the prognosis remains poor, especially in cases dominated by cardiomyopathy. Genetics play a central role in the disease›s transmission, with autosomal-dominant inheritance patterns and high penetrance among carriers of pathogenic mutations. Research continues to uncover the broad spectrum of genetic variations contributing to hATTR amyloidosis, with ongoing studies poised to expand our understanding of its molecular underpinnings and potential treatment options.

4. The effect on quality of life is significant both in patients living with hATTR amyloidosis and their caregivers.

hATTR amyloidosis imposes a multifaceted burden on patients and their caregivers as the disease progresses. Symptoms range from sensorimotor impairment and gastrointestinal or autonomic dysfunction to heart failure, leading to significant health-related quality-of-life deficits. The systemic nature of hATTR amyloidosis significantly affects patients› lifestyles, daily activities, and general well-being, especially because it typically manifests in adulthood — a crucial time for occupational changes. The progression of hATTR amyloidosis exacerbates the challenges in maintaining employment and managing household chores, with symptomatic patients often unable to work and experiencing difficulties with absenteeism and presenteeism when they are able to work.

hATTR amyloidosis leads to physical, mental, occupational, and social limitations for patients, and it also places a considerable strain on their families and caregivers, who report poor mental health, work impairment, and a high time commitment (mean, 45.9 h/wk) to providing care.

5. There have been significant advancements in therapeutic options for early-stage hATTR amyloidosis.

After diagnosis, prompt initiation of treatment is recommended to delay the progression of hATTR amyloidosis; a multidisciplinary approach is essential, incorporating anti-amyloid therapy to inhibit further production and/or deposition of amyloid aggregates. Treatment strategies also include addressing symptomatic therapy and managing cardiac, renal, and ocular involvement. Although many therapies have been developed, especially for the early stages of hATTR amyloidosis, therapeutic benefits for patients with advanced disease remain limited.

Recent advancements in the treatment of hATTR amyloidosis have introduced RNA-targeted therapies including patisiran, vutrisiran, and eplontersen, which have shown efficacy in reducing hepatic TTR synthesis and the aggregation of misfolded monomers into amyloid deposits. These therapies, ranging from small interfering RNA formulations to antisense oligonucleotides, offer benefits in managing both cardiomyopathy and neuropathy associated with hATTR amyloidosis , administered through various methods, including intravenous infusions and subcutaneous injections. In addition, the stabilization of TTR tetramers with the use of drugs such as tafamidis and diflunisal has effectively prevented the formation of amyloidogenic monomers. Moreover, other investigational agents, including TTR stabilizers like acoramidis and tolcapone, as well as novel compounds that inhibit amyloid formation and disrupt fibrils, are expanding the therapeutic landscape for hATTR amyloidosis , providing hope for improved management of this complex condition.

Dr. Gertz is a professor and consultant in the Department of Hematology, Mayo Clinic, Rochester, Minnesota. He has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from AstraZeneca, Ionis, and Alnylym.

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The authors had no disclosures to report.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The authors had no disclosures to report.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The authors had no disclosures to report.

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