Cardiology News

Rising consolidation among pharmacy benefit managers (PBMs) allows the companies to profit at the expense of patients and independent pharmacists. That’s the conclusion of a recent Federal Trade Commission (FTC) report on interim findings from the agency’s ongoing investigation of PBMs. 

Lawmakers are increasingly scrutinizing the industry amid growing concern among physicians and consumers about how PBMs exploit their market dominance. The top six PBMs managed 94% of US drug claims in 2023, with the majority handled by the industry’s three giants: CVS Caremark, Cigna’s Express Scripts, and United Healthcare’s OptumRx.

PBMs manage prescription drug benefits for health insurers, Medicare Part D drug plans, and large employers. They act as middlemen between health insurers and pharmacies, developing formularies of covered drugs and promising savings from the discounts and rebates they negotiate with drugmakers.

The FTC’s interim report found that the giant PBMs often exercise significant control over what drugs are available and at what price and which pharmacies patients can use to access their prescribed medications. Consumers suffer as a result, the report concluded.

Madelaine A. Feldman, MD, vice president for advocacy and government affairs for the Coalition of State Rheumatology Organizations, shared her perspective on the FTC report in an email Q&A with this news organization. She is affiliated with The Rheumatology Group, based in Metairie, Louisiana. 

Dr. Feldman has long tracked the PBM industry and appeared as a witness before influential government panels, including the House Energy and Commerce Committee. She has highlighted for lawmakers the challenges physicians face in helping patients get needed medicines. 

For example, she shared cases of PBMs steering patients toward the more expensive of three widely used rheumatoid arthritis medicines that have a similar mechanism of action, the Janus kinase (JAK) inhibitors, Dr. Feldman said. 

One of the drugs cost roughly half of the other two — about $30,000 per year vs $65,000-$70,000. Yet only the two expensive drugs were included in the PBM formulary. As a result, the cheapest drug holds only a sliver of market share; the remainder is dominated by the two expensive products, she told the House Oversight and Accountability Committee in 2021.

This Q&A has been edited for length and clarity.

What would you want federal and state policymakers to do in response to the FTC’s report?

I think Congress needs to clearly delineate the differences between anticompetitive pharmacy issues, drug pricing issues, and their effect on formulary construction issues.

Lawmakers should demand more transparency and consider legislation that would remove perverse incentives that prompt PBMs to choose higher priced drugs for their formularies. 

That may require other regulatory or legislative actions to ensure lower prices (not higher kickbacks) are incentivized. Ultimately, in order to gain true competition within the health insurance business, these oligopolies of multiple businesses need to be broken up. Anything less seems to be nibbling around the edges and allows the Big Three to continue their “whack-a mole” in circumventing piecemeal regulatory and legislative policies.

You’ve followed PBM practices closely for many years. Was there anything in this interim FTC report that surprised you?

Though not surprised, I am glad that it was released because it had been a year in investigation and there were many requests for some type of substantive report. 

Two things that are missing that I feel are paramount are investigating how the three big PBMs are causing physical harm to patients as a result of the profit component in formulary construction and the profound financial impact of hidden PBM profit centers in self-insured employer health plans.

What we have seen over the years is the result of the perverse incentives for the PBMs to prefer the most profitable medications on their formularies. 

They use utilization management tools such as step therapy, nonmedical switching, and exclusions to maintain their formularies’ profitability. These tools have been shown to delay and deny the proper care of patients, resulting in not just monetary but physical harm as well. 

I would think the physical harm done to patients in manipulating the formularies should be addressed in this report as well and, in fact, may be the most important aspect of consumer protection of this issue.

In terms of the FTC’s mission to not “unduly burden” legitimate business, I would like to see the sector of self-insured employers addressed. 

The report details how PBMs steer prescriptions to their affiliated pharmacies. The FTC says that can push smaller pharmacies out of the market, ultimately leading to higher costs and lower quality services for people. What’s your perspective? 

Having more community pharmacies is better than having less. We are seeing more “pharmacy deserts” in rural areas as a result of many community pharmacies having to close.

The FTC voted 4-1 to allow staff to issue the interim report, with Commissioner Melissa Holyoak voting no. And some FTC commissioners seem divided on the usefulness of the report. Why?

Commissioner Holyoak states the “the Report leaves us without a better understanding of the competition concerns surrounding PBMs or how consumers are impacted by PBM practices.” 

I do agree with her that the harm to patients’ medical status was not even addressed as far as I could tell in this report. There are multiple news articles and reports on the harms inflicted upon patients by the UM tools that drive the construction of ever changing formularies, all based on contracting with manufacturers that result in the highest profit for the PBM.

Holyoak also states, “Among other critical conclusions, the Report does not address the seemingly contradictory conclusions in the 2005 Report that PBMs, including vertically owned PBMs, generated cost savings for consumers.” 

That may be true, but in 2005, the rise of PBMs was just beginning and the huge vertical and horizontal integration had yet to begin. Also, 2005 was still in the beginning of the biologic drug deluge, which did create competition to get on the formulary. Since then, PBMs have done nothing to control the rise in prices but instead, apparently have used the competition to get higher price concessions from manufacturers based on a percentage of the list price to line their pockets.

Commissioner Ferguson agreed with releasing the report but he had many issues with this report including the lack of PBM response. 

I do agree with him that the FTC should have used some type of “force” to get the information they needed from the PBMs. The Big Three are known for obfuscation and delaying providing information to legislative and regulatory agencies.
 

A version of this article appeared on Medscape.com.

Rising consolidation among pharmacy benefit managers (PBMs) allows the companies to profit at the expense of patients and independent pharmacists. That’s the conclusion of a recent Federal Trade Commission (FTC) report on interim findings from the agency’s ongoing investigation of PBMs. 

Lawmakers are increasingly scrutinizing the industry amid growing concern among physicians and consumers about how PBMs exploit their market dominance. The top six PBMs managed 94% of US drug claims in 2023, with the majority handled by the industry’s three giants: CVS Caremark, Cigna’s Express Scripts, and United Healthcare’s OptumRx.

PBMs manage prescription drug benefits for health insurers, Medicare Part D drug plans, and large employers. They act as middlemen between health insurers and pharmacies, developing formularies of covered drugs and promising savings from the discounts and rebates they negotiate with drugmakers.

The FTC’s interim report found that the giant PBMs often exercise significant control over what drugs are available and at what price and which pharmacies patients can use to access their prescribed medications. Consumers suffer as a result, the report concluded.

Madelaine A. Feldman, MD, vice president for advocacy and government affairs for the Coalition of State Rheumatology Organizations, shared her perspective on the FTC report in an email Q&A with this news organization. She is affiliated with The Rheumatology Group, based in Metairie, Louisiana. 

Dr. Feldman has long tracked the PBM industry and appeared as a witness before influential government panels, including the House Energy and Commerce Committee. She has highlighted for lawmakers the challenges physicians face in helping patients get needed medicines. 

For example, she shared cases of PBMs steering patients toward the more expensive of three widely used rheumatoid arthritis medicines that have a similar mechanism of action, the Janus kinase (JAK) inhibitors, Dr. Feldman said. 

One of the drugs cost roughly half of the other two — about $30,000 per year vs $65,000-$70,000. Yet only the two expensive drugs were included in the PBM formulary. As a result, the cheapest drug holds only a sliver of market share; the remainder is dominated by the two expensive products, she told the House Oversight and Accountability Committee in 2021.

This Q&A has been edited for length and clarity.

What would you want federal and state policymakers to do in response to the FTC’s report?

I think Congress needs to clearly delineate the differences between anticompetitive pharmacy issues, drug pricing issues, and their effect on formulary construction issues.

Lawmakers should demand more transparency and consider legislation that would remove perverse incentives that prompt PBMs to choose higher priced drugs for their formularies. 

That may require other regulatory or legislative actions to ensure lower prices (not higher kickbacks) are incentivized. Ultimately, in order to gain true competition within the health insurance business, these oligopolies of multiple businesses need to be broken up. Anything less seems to be nibbling around the edges and allows the Big Three to continue their “whack-a mole” in circumventing piecemeal regulatory and legislative policies.

You’ve followed PBM practices closely for many years. Was there anything in this interim FTC report that surprised you?

Though not surprised, I am glad that it was released because it had been a year in investigation and there were many requests for some type of substantive report. 

Two things that are missing that I feel are paramount are investigating how the three big PBMs are causing physical harm to patients as a result of the profit component in formulary construction and the profound financial impact of hidden PBM profit centers in self-insured employer health plans.

What we have seen over the years is the result of the perverse incentives for the PBMs to prefer the most profitable medications on their formularies. 

They use utilization management tools such as step therapy, nonmedical switching, and exclusions to maintain their formularies’ profitability. These tools have been shown to delay and deny the proper care of patients, resulting in not just monetary but physical harm as well. 

I would think the physical harm done to patients in manipulating the formularies should be addressed in this report as well and, in fact, may be the most important aspect of consumer protection of this issue.

In terms of the FTC’s mission to not “unduly burden” legitimate business, I would like to see the sector of self-insured employers addressed. 

The report details how PBMs steer prescriptions to their affiliated pharmacies. The FTC says that can push smaller pharmacies out of the market, ultimately leading to higher costs and lower quality services for people. What’s your perspective? 

Having more community pharmacies is better than having less. We are seeing more “pharmacy deserts” in rural areas as a result of many community pharmacies having to close.

The FTC voted 4-1 to allow staff to issue the interim report, with Commissioner Melissa Holyoak voting no. And some FTC commissioners seem divided on the usefulness of the report. Why?

Commissioner Holyoak states the “the Report leaves us without a better understanding of the competition concerns surrounding PBMs or how consumers are impacted by PBM practices.” 

I do agree with her that the harm to patients’ medical status was not even addressed as far as I could tell in this report. There are multiple news articles and reports on the harms inflicted upon patients by the UM tools that drive the construction of ever changing formularies, all based on contracting with manufacturers that result in the highest profit for the PBM.

Holyoak also states, “Among other critical conclusions, the Report does not address the seemingly contradictory conclusions in the 2005 Report that PBMs, including vertically owned PBMs, generated cost savings for consumers.” 

That may be true, but in 2005, the rise of PBMs was just beginning and the huge vertical and horizontal integration had yet to begin. Also, 2005 was still in the beginning of the biologic drug deluge, which did create competition to get on the formulary. Since then, PBMs have done nothing to control the rise in prices but instead, apparently have used the competition to get higher price concessions from manufacturers based on a percentage of the list price to line their pockets.

Commissioner Ferguson agreed with releasing the report but he had many issues with this report including the lack of PBM response. 

I do agree with him that the FTC should have used some type of “force” to get the information they needed from the PBMs. The Big Three are known for obfuscation and delaying providing information to legislative and regulatory agencies.
 

A version of this article appeared on Medscape.com.

Rising consolidation among pharmacy benefit managers (PBMs) allows the companies to profit at the expense of patients and independent pharmacists. That’s the conclusion of a recent Federal Trade Commission (FTC) report on interim findings from the agency’s ongoing investigation of PBMs. 

Lawmakers are increasingly scrutinizing the industry amid growing concern among physicians and consumers about how PBMs exploit their market dominance. The top six PBMs managed 94% of US drug claims in 2023, with the majority handled by the industry’s three giants: CVS Caremark, Cigna’s Express Scripts, and United Healthcare’s OptumRx.

PBMs manage prescription drug benefits for health insurers, Medicare Part D drug plans, and large employers. They act as middlemen between health insurers and pharmacies, developing formularies of covered drugs and promising savings from the discounts and rebates they negotiate with drugmakers.

The FTC’s interim report found that the giant PBMs often exercise significant control over what drugs are available and at what price and which pharmacies patients can use to access their prescribed medications. Consumers suffer as a result, the report concluded.

Madelaine A. Feldman, MD, vice president for advocacy and government affairs for the Coalition of State Rheumatology Organizations, shared her perspective on the FTC report in an email Q&A with this news organization. She is affiliated with The Rheumatology Group, based in Metairie, Louisiana. 

Dr. Feldman has long tracked the PBM industry and appeared as a witness before influential government panels, including the House Energy and Commerce Committee. She has highlighted for lawmakers the challenges physicians face in helping patients get needed medicines. 

For example, she shared cases of PBMs steering patients toward the more expensive of three widely used rheumatoid arthritis medicines that have a similar mechanism of action, the Janus kinase (JAK) inhibitors, Dr. Feldman said. 

One of the drugs cost roughly half of the other two — about $30,000 per year vs $65,000-$70,000. Yet only the two expensive drugs were included in the PBM formulary. As a result, the cheapest drug holds only a sliver of market share; the remainder is dominated by the two expensive products, she told the House Oversight and Accountability Committee in 2021.

This Q&A has been edited for length and clarity.

What would you want federal and state policymakers to do in response to the FTC’s report?

I think Congress needs to clearly delineate the differences between anticompetitive pharmacy issues, drug pricing issues, and their effect on formulary construction issues.

Lawmakers should demand more transparency and consider legislation that would remove perverse incentives that prompt PBMs to choose higher priced drugs for their formularies. 

That may require other regulatory or legislative actions to ensure lower prices (not higher kickbacks) are incentivized. Ultimately, in order to gain true competition within the health insurance business, these oligopolies of multiple businesses need to be broken up. Anything less seems to be nibbling around the edges and allows the Big Three to continue their “whack-a mole” in circumventing piecemeal regulatory and legislative policies.

You’ve followed PBM practices closely for many years. Was there anything in this interim FTC report that surprised you?

Though not surprised, I am glad that it was released because it had been a year in investigation and there were many requests for some type of substantive report. 

Two things that are missing that I feel are paramount are investigating how the three big PBMs are causing physical harm to patients as a result of the profit component in formulary construction and the profound financial impact of hidden PBM profit centers in self-insured employer health plans.

What we have seen over the years is the result of the perverse incentives for the PBMs to prefer the most profitable medications on their formularies. 

They use utilization management tools such as step therapy, nonmedical switching, and exclusions to maintain their formularies’ profitability. These tools have been shown to delay and deny the proper care of patients, resulting in not just monetary but physical harm as well. 

I would think the physical harm done to patients in manipulating the formularies should be addressed in this report as well and, in fact, may be the most important aspect of consumer protection of this issue.

In terms of the FTC’s mission to not “unduly burden” legitimate business, I would like to see the sector of self-insured employers addressed. 

The report details how PBMs steer prescriptions to their affiliated pharmacies. The FTC says that can push smaller pharmacies out of the market, ultimately leading to higher costs and lower quality services for people. What’s your perspective? 

Having more community pharmacies is better than having less. We are seeing more “pharmacy deserts” in rural areas as a result of many community pharmacies having to close.

The FTC voted 4-1 to allow staff to issue the interim report, with Commissioner Melissa Holyoak voting no. And some FTC commissioners seem divided on the usefulness of the report. Why?

Commissioner Holyoak states the “the Report leaves us without a better understanding of the competition concerns surrounding PBMs or how consumers are impacted by PBM practices.” 

I do agree with her that the harm to patients’ medical status was not even addressed as far as I could tell in this report. There are multiple news articles and reports on the harms inflicted upon patients by the UM tools that drive the construction of ever changing formularies, all based on contracting with manufacturers that result in the highest profit for the PBM.

Holyoak also states, “Among other critical conclusions, the Report does not address the seemingly contradictory conclusions in the 2005 Report that PBMs, including vertically owned PBMs, generated cost savings for consumers.” 

That may be true, but in 2005, the rise of PBMs was just beginning and the huge vertical and horizontal integration had yet to begin. Also, 2005 was still in the beginning of the biologic drug deluge, which did create competition to get on the formulary. Since then, PBMs have done nothing to control the rise in prices but instead, apparently have used the competition to get higher price concessions from manufacturers based on a percentage of the list price to line their pockets.

Commissioner Ferguson agreed with releasing the report but he had many issues with this report including the lack of PBM response. 

I do agree with him that the FTC should have used some type of “force” to get the information they needed from the PBMs. The Big Three are known for obfuscation and delaying providing information to legislative and regulatory agencies.
 

A version of this article appeared on Medscape.com.

What if a drug could help you live a longer, healthier life?

Scientists at the University of Connecticut are working on it. In a new study in Cell Metabolism, researchers described how to target specific cells to extend the lifespan and improve the health of mice late in life.

The study builds on a growing body of research, mostly in animals, testing interventions to slow aging and prolong health span, the length of time that one is not just alive but also healthy.

“Aging is the most important risk factor for every disease that we deal with in adult human beings,” said cardiologist Douglas Vaughan, MD, director of the Potocsnak Longevity Institute at Northwestern University’s Feinberg School of Medicine, Chicago. (Dr. Vaughan was not involved in the new study.) “So the big hypothesis is: If we could slow down aging just a little bit, we can push back the onset of disease.”

As we age, our cells wear out. It’s called cellular senescence — a state of irreversible cell cycle arrest — and it’s increasingly recognized as a key contributor to aging.

Senescent cells — or “zombie cells” — secrete harmful substances that disrupt tissue functioning. They’ve been linked to chronic inflammation, tissue damage, and the development of age-related diseases.

Senescence can be characterized by the accumulation of cells with high levels of specific markers like p21, or p21^high cells. Almost any cell can become a p21^high cell, and they accumulate with age, said Ming Xu, PhD, a professor at the UConn Center on Aging, UConn Health, Farmington, Connecticut, who led the study.

By targeting and eliminating p21^high senescent cells, Dr. Xu hopes to develop novel therapies that might help people live longer and enjoy more years in good health.

Such a treatment could be ready for human trials in 2-5 years, Dr. Xu said.
 

What the Researchers Did

Xu and colleagues used genetic engineering to eliminate p21^high cells in mice, introducing into their genome something they describe as an inducible “suicide gene.” Giving the mice a certain drug (a low dose of tamoxifen) activated the suicide gene in all p21^high cells, causing them to die. Administering this treatment once a month, from age 20 months (older age) until the end of life, significantly extended the rodents’ lifespan, reduced inflammation, and decreased gene activity linked to aging.

Treated mice lived, on average, for 33 months — 3 months longer than the untreated mice. The oldest treated mouse lived to 43 months — roughly 130 in human years.

But the treated mice didn’t just live longer; they were also healthier. In humans, walking speed and grip strength can be clues of overall health and vitality. The old, treated mice were able to walk faster and grip objects with greater strength than untreated mice of the same age.

Dr. Xu’s lab is now testing drugs that target p21^high cells in hopes of finding one that would work in humans. Leveraging immunotherapy technology to target these cells could be another option, Dr. Xu said.

The team also plans to test whether eliminating p21^high cells could prevent or alleviate diabetes or Alzheimer’s disease.
 

Challenges and Criticisms

The research provides “important evidence that targeting senescence and the molecular components of that pathway might provide some benefit in the long term,” Dr. Vaughan said.

But killing senescent cells could come with downsides.

“Senescence protects us from hyperproliferative responses,” potentially blocking cells from becoming malignant, Dr. Vaughan said. “There’s this effect on aging that is desirable, but at the same time, you may enhance your risk of cancer or malignancy or excessive proliferation in some cells.”

And of course, we don’t necessarily need drugs to prolong healthy life, Dr. Vaughan pointed out.

For many people, a long healthy life is already within reach. Humans live longer on average than they used to, and simple lifestyle choices — nourishing your body well, staying active, and maintaining a healthy weight — can increase one’s chances of good health.

The most consistently demonstrated intervention for extending lifespan “in almost every animal species is caloric restriction,” Dr. Vaughan said. (Dr. Xu’s team is also investigating whether fasting and exercise can lead to a decrease in p21^high cells.)

As for brain health, Dr. Vaughan and colleagues at Northwestern are studying “super agers,” people who are cognitively intact into their 90s.

“The one single thing that they found that contributes to that process, and contributes to that success, is really a social network and human bonds and interaction,” Dr. Vaughan said.

A version of this article appeared on Medscape.com.

What if a drug could help you live a longer, healthier life?

Scientists at the University of Connecticut are working on it. In a new study in Cell Metabolism, researchers described how to target specific cells to extend the lifespan and improve the health of mice late in life.

The study builds on a growing body of research, mostly in animals, testing interventions to slow aging and prolong health span, the length of time that one is not just alive but also healthy.

“Aging is the most important risk factor for every disease that we deal with in adult human beings,” said cardiologist Douglas Vaughan, MD, director of the Potocsnak Longevity Institute at Northwestern University’s Feinberg School of Medicine, Chicago. (Dr. Vaughan was not involved in the new study.) “So the big hypothesis is: If we could slow down aging just a little bit, we can push back the onset of disease.”

As we age, our cells wear out. It’s called cellular senescence — a state of irreversible cell cycle arrest — and it’s increasingly recognized as a key contributor to aging.

Senescent cells — or “zombie cells” — secrete harmful substances that disrupt tissue functioning. They’ve been linked to chronic inflammation, tissue damage, and the development of age-related diseases.

Senescence can be characterized by the accumulation of cells with high levels of specific markers like p21, or p21^high cells. Almost any cell can become a p21^high cell, and they accumulate with age, said Ming Xu, PhD, a professor at the UConn Center on Aging, UConn Health, Farmington, Connecticut, who led the study.

By targeting and eliminating p21^high senescent cells, Dr. Xu hopes to develop novel therapies that might help people live longer and enjoy more years in good health.

Such a treatment could be ready for human trials in 2-5 years, Dr. Xu said.
 

What the Researchers Did

Xu and colleagues used genetic engineering to eliminate p21^high cells in mice, introducing into their genome something they describe as an inducible “suicide gene.” Giving the mice a certain drug (a low dose of tamoxifen) activated the suicide gene in all p21^high cells, causing them to die. Administering this treatment once a month, from age 20 months (older age) until the end of life, significantly extended the rodents’ lifespan, reduced inflammation, and decreased gene activity linked to aging.

Treated mice lived, on average, for 33 months — 3 months longer than the untreated mice. The oldest treated mouse lived to 43 months — roughly 130 in human years.

But the treated mice didn’t just live longer; they were also healthier. In humans, walking speed and grip strength can be clues of overall health and vitality. The old, treated mice were able to walk faster and grip objects with greater strength than untreated mice of the same age.

Dr. Xu’s lab is now testing drugs that target p21^high cells in hopes of finding one that would work in humans. Leveraging immunotherapy technology to target these cells could be another option, Dr. Xu said.

The team also plans to test whether eliminating p21^high cells could prevent or alleviate diabetes or Alzheimer’s disease.
 

Challenges and Criticisms

The research provides “important evidence that targeting senescence and the molecular components of that pathway might provide some benefit in the long term,” Dr. Vaughan said.

But killing senescent cells could come with downsides.

“Senescence protects us from hyperproliferative responses,” potentially blocking cells from becoming malignant, Dr. Vaughan said. “There’s this effect on aging that is desirable, but at the same time, you may enhance your risk of cancer or malignancy or excessive proliferation in some cells.”

And of course, we don’t necessarily need drugs to prolong healthy life, Dr. Vaughan pointed out.

For many people, a long healthy life is already within reach. Humans live longer on average than they used to, and simple lifestyle choices — nourishing your body well, staying active, and maintaining a healthy weight — can increase one’s chances of good health.

The most consistently demonstrated intervention for extending lifespan “in almost every animal species is caloric restriction,” Dr. Vaughan said. (Dr. Xu’s team is also investigating whether fasting and exercise can lead to a decrease in p21^high cells.)

As for brain health, Dr. Vaughan and colleagues at Northwestern are studying “super agers,” people who are cognitively intact into their 90s.

“The one single thing that they found that contributes to that process, and contributes to that success, is really a social network and human bonds and interaction,” Dr. Vaughan said.

A version of this article appeared on Medscape.com.

What if a drug could help you live a longer, healthier life?

Scientists at the University of Connecticut are working on it. In a new study in Cell Metabolism, researchers described how to target specific cells to extend the lifespan and improve the health of mice late in life.

The study builds on a growing body of research, mostly in animals, testing interventions to slow aging and prolong health span, the length of time that one is not just alive but also healthy.

“Aging is the most important risk factor for every disease that we deal with in adult human beings,” said cardiologist Douglas Vaughan, MD, director of the Potocsnak Longevity Institute at Northwestern University’s Feinberg School of Medicine, Chicago. (Dr. Vaughan was not involved in the new study.) “So the big hypothesis is: If we could slow down aging just a little bit, we can push back the onset of disease.”

As we age, our cells wear out. It’s called cellular senescence — a state of irreversible cell cycle arrest — and it’s increasingly recognized as a key contributor to aging.

Senescent cells — or “zombie cells” — secrete harmful substances that disrupt tissue functioning. They’ve been linked to chronic inflammation, tissue damage, and the development of age-related diseases.

Senescence can be characterized by the accumulation of cells with high levels of specific markers like p21, or p21^high cells. Almost any cell can become a p21^high cell, and they accumulate with age, said Ming Xu, PhD, a professor at the UConn Center on Aging, UConn Health, Farmington, Connecticut, who led the study.

By targeting and eliminating p21^high senescent cells, Dr. Xu hopes to develop novel therapies that might help people live longer and enjoy more years in good health.

Such a treatment could be ready for human trials in 2-5 years, Dr. Xu said.
 

What the Researchers Did

Xu and colleagues used genetic engineering to eliminate p21^high cells in mice, introducing into their genome something they describe as an inducible “suicide gene.” Giving the mice a certain drug (a low dose of tamoxifen) activated the suicide gene in all p21^high cells, causing them to die. Administering this treatment once a month, from age 20 months (older age) until the end of life, significantly extended the rodents’ lifespan, reduced inflammation, and decreased gene activity linked to aging.

Treated mice lived, on average, for 33 months — 3 months longer than the untreated mice. The oldest treated mouse lived to 43 months — roughly 130 in human years.

But the treated mice didn’t just live longer; they were also healthier. In humans, walking speed and grip strength can be clues of overall health and vitality. The old, treated mice were able to walk faster and grip objects with greater strength than untreated mice of the same age.

Dr. Xu’s lab is now testing drugs that target p21^high cells in hopes of finding one that would work in humans. Leveraging immunotherapy technology to target these cells could be another option, Dr. Xu said.

The team also plans to test whether eliminating p21^high cells could prevent or alleviate diabetes or Alzheimer’s disease.
 

Challenges and Criticisms

The research provides “important evidence that targeting senescence and the molecular components of that pathway might provide some benefit in the long term,” Dr. Vaughan said.

But killing senescent cells could come with downsides.

“Senescence protects us from hyperproliferative responses,” potentially blocking cells from becoming malignant, Dr. Vaughan said. “There’s this effect on aging that is desirable, but at the same time, you may enhance your risk of cancer or malignancy or excessive proliferation in some cells.”

And of course, we don’t necessarily need drugs to prolong healthy life, Dr. Vaughan pointed out.

For many people, a long healthy life is already within reach. Humans live longer on average than they used to, and simple lifestyle choices — nourishing your body well, staying active, and maintaining a healthy weight — can increase one’s chances of good health.

The most consistently demonstrated intervention for extending lifespan “in almost every animal species is caloric restriction,” Dr. Vaughan said. (Dr. Xu’s team is also investigating whether fasting and exercise can lead to a decrease in p21^high cells.)

As for brain health, Dr. Vaughan and colleagues at Northwestern are studying “super agers,” people who are cognitively intact into their 90s.

“The one single thing that they found that contributes to that process, and contributes to that success, is really a social network and human bonds and interaction,” Dr. Vaughan said.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with type 2 diabetes (T2D), eating more ultraprocessed food (UPF) increased the overall risk for microvascular complications and for diabetic kidney disease in particular. The risk was partly mediated by biomarkers related to body weight, lipid metabolism, and inflammation.

METHODOLOGY:

• A higher intake of UPF increases the risk for T2D and other metabolic morbidities; but whether this leads to an increased risk for diabetic microvascular complications remains largely unexplored.
• Researchers evaluated the association between the intake of UPF and the risk for diabetic microvascular complications in a prospective cohort of 5685 participants with T2D (mean age, 59.7 years; 63.8% men) from the UK Biobank.
• Dietary information of participants was collected with a web-based 24-hour dietary recall tool that recorded the frequency of consumption of 206 foods and 32 beverages.
• Researchers found five patterns that accounted for one third of UPF intake variation by estimated weight (not calories): Bread and spreads; cereal with liquids; high dairy and low cured meat; sugary beverages and snacks; and mixed beverages and savory snacks.
• The outcomes included the risk for overall microvascular complications; for diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease; and for biomarkers related to microvascular complications.

TAKEAWAY:

• During a median follow-up duration of 12.7 years, 1243 composite microvascular complications were reported, including 599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events.
• Each 10% increase in the proportion of UPF consumption increased the risk for composite microvascular complications by 8% (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13) and diabetic kidney disease by 13% (HR 1.13; 95% CI, 1.06-1.20). No significant UPF intake association was found with diabetic retinopathy or diabetic neuropathy.
• In the biomarker mediation analysis, body mass index, triglycerides, and C-reactive protein collectively explained 22% (P < .001) and 15.8% (P < .001) of the associations of UPF consumption with composite microvascular complications and diabetic kidney disease, respectively.
• The food pattern rich in sugary beverages and snacks increased the risk for diabetic kidney disease, whereas the pattern rich in mixed beverages and savory snacks increased the risk for composite microvascular complications and diabetic retinopathy.

IN PRACTICE:

“In view of microvascular complications, our findings further support adhering to the recommendations outlined in the American Diabetes Association’s 2022 guidelines, which advocate for the preference of whole foods over highly processed ones,” the authors wrote.

SOURCE:

The study was led by Yue Li, MBBS, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. It was published online in The American Journal of Clinical Nutrition.

LIMITATIONS:

The dietary recall used in the UK Biobank was not specifically designed to collect dietary data according to the Nova food categories used in the study, which may have led to misclassifications. Data on usual dietary intake may not have been captured accurately, as all participants did not provide multiple dietary recalls. Individuals with T2D who completed dietary assessments were more likely to have a higher socioeconomic status and healthier lifestyle than those not filling the assessment, which could have resulted in an underrepresentation of high UPF consumers.

DISCLOSURES:

Some authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, and other government sources. None of the authors declared any competing interests.
 

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

TOPLINE:

In patients with type 2 diabetes (T2D), eating more ultraprocessed food (UPF) increased the overall risk for microvascular complications and for diabetic kidney disease in particular. The risk was partly mediated by biomarkers related to body weight, lipid metabolism, and inflammation.

METHODOLOGY:

• A higher intake of UPF increases the risk for T2D and other metabolic morbidities; but whether this leads to an increased risk for diabetic microvascular complications remains largely unexplored.
• Researchers evaluated the association between the intake of UPF and the risk for diabetic microvascular complications in a prospective cohort of 5685 participants with T2D (mean age, 59.7 years; 63.8% men) from the UK Biobank.
• Dietary information of participants was collected with a web-based 24-hour dietary recall tool that recorded the frequency of consumption of 206 foods and 32 beverages.
• Researchers found five patterns that accounted for one third of UPF intake variation by estimated weight (not calories): Bread and spreads; cereal with liquids; high dairy and low cured meat; sugary beverages and snacks; and mixed beverages and savory snacks.
• The outcomes included the risk for overall microvascular complications; for diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease; and for biomarkers related to microvascular complications.

TAKEAWAY:

• During a median follow-up duration of 12.7 years, 1243 composite microvascular complications were reported, including 599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events.
• Each 10% increase in the proportion of UPF consumption increased the risk for composite microvascular complications by 8% (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13) and diabetic kidney disease by 13% (HR 1.13; 95% CI, 1.06-1.20). No significant UPF intake association was found with diabetic retinopathy or diabetic neuropathy.
• In the biomarker mediation analysis, body mass index, triglycerides, and C-reactive protein collectively explained 22% (P < .001) and 15.8% (P < .001) of the associations of UPF consumption with composite microvascular complications and diabetic kidney disease, respectively.
• The food pattern rich in sugary beverages and snacks increased the risk for diabetic kidney disease, whereas the pattern rich in mixed beverages and savory snacks increased the risk for composite microvascular complications and diabetic retinopathy.

IN PRACTICE:

“In view of microvascular complications, our findings further support adhering to the recommendations outlined in the American Diabetes Association’s 2022 guidelines, which advocate for the preference of whole foods over highly processed ones,” the authors wrote.

SOURCE:

The study was led by Yue Li, MBBS, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. It was published online in The American Journal of Clinical Nutrition.

LIMITATIONS:

The dietary recall used in the UK Biobank was not specifically designed to collect dietary data according to the Nova food categories used in the study, which may have led to misclassifications. Data on usual dietary intake may not have been captured accurately, as all participants did not provide multiple dietary recalls. Individuals with T2D who completed dietary assessments were more likely to have a higher socioeconomic status and healthier lifestyle than those not filling the assessment, which could have resulted in an underrepresentation of high UPF consumers.

DISCLOSURES:

Some authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, and other government sources. None of the authors declared any competing interests.
 

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

TOPLINE:

In patients with type 2 diabetes (T2D), eating more ultraprocessed food (UPF) increased the overall risk for microvascular complications and for diabetic kidney disease in particular. The risk was partly mediated by biomarkers related to body weight, lipid metabolism, and inflammation.

METHODOLOGY:

• A higher intake of UPF increases the risk for T2D and other metabolic morbidities; but whether this leads to an increased risk for diabetic microvascular complications remains largely unexplored.
• Researchers evaluated the association between the intake of UPF and the risk for diabetic microvascular complications in a prospective cohort of 5685 participants with T2D (mean age, 59.7 years; 63.8% men) from the UK Biobank.
• Dietary information of participants was collected with a web-based 24-hour dietary recall tool that recorded the frequency of consumption of 206 foods and 32 beverages.
• Researchers found five patterns that accounted for one third of UPF intake variation by estimated weight (not calories): Bread and spreads; cereal with liquids; high dairy and low cured meat; sugary beverages and snacks; and mixed beverages and savory snacks.
• The outcomes included the risk for overall microvascular complications; for diabetic retinopathy, diabetic neuropathy, and diabetic kidney disease; and for biomarkers related to microvascular complications.

TAKEAWAY:

• During a median follow-up duration of 12.7 years, 1243 composite microvascular complications were reported, including 599 diabetic retinopathy, 237 diabetic neuropathy, and 662 diabetic kidney disease events.
• Each 10% increase in the proportion of UPF consumption increased the risk for composite microvascular complications by 8% (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13) and diabetic kidney disease by 13% (HR 1.13; 95% CI, 1.06-1.20). No significant UPF intake association was found with diabetic retinopathy or diabetic neuropathy.
• In the biomarker mediation analysis, body mass index, triglycerides, and C-reactive protein collectively explained 22% (P < .001) and 15.8% (P < .001) of the associations of UPF consumption with composite microvascular complications and diabetic kidney disease, respectively.
• The food pattern rich in sugary beverages and snacks increased the risk for diabetic kidney disease, whereas the pattern rich in mixed beverages and savory snacks increased the risk for composite microvascular complications and diabetic retinopathy.

IN PRACTICE:

“In view of microvascular complications, our findings further support adhering to the recommendations outlined in the American Diabetes Association’s 2022 guidelines, which advocate for the preference of whole foods over highly processed ones,” the authors wrote.

SOURCE:

The study was led by Yue Li, MBBS, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. It was published online in The American Journal of Clinical Nutrition.

LIMITATIONS:

The dietary recall used in the UK Biobank was not specifically designed to collect dietary data according to the Nova food categories used in the study, which may have led to misclassifications. Data on usual dietary intake may not have been captured accurately, as all participants did not provide multiple dietary recalls. Individuals with T2D who completed dietary assessments were more likely to have a higher socioeconomic status and healthier lifestyle than those not filling the assessment, which could have resulted in an underrepresentation of high UPF consumers.

DISCLOSURES:

Some authors received funding from the National Natural Science Foundation of China, the National Key Research and Development Program of China, and other government sources. None of the authors declared any competing interests.
 

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

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

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

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

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

The Heritage Foundation sponsored and developed Project 2025 for the explicit, stated purpose of building a conservative victory through policy, personnel, and training with a 180-day game plan after a sympathetic new President of the United States takes office. To date, Project 2025 has not been formally endorsed by any presidential campaign.

More than 100 conservative organizations are said to be participating. More than 400 conservative scholars and experts have collaborated in authorship of the mandate’s 40 chapters. Chapter 14 of the “Mandate for Leadership” is an exhaustive proposed overhaul of the Department of Health and Human Services (HHS), one of the major existing arms of the executive branch of the US government. 

The mandate’s sweeping recommendations, if implemented, would impact the lives of all Americans and all healthcare workers, as outlined in the following excerpts. 
 

Healthcare-Related Excerpts From Project 2025

• “From the moment of conception, every human being possesses inherent dignity and worth, and our humanity does not depend on our age, stage of development, race, or abilities. The Secretary must ensure that all HHS programs and activities are rooted in a deep respect for innocent human life from day one until natural death: Abortion and euthanasia are not health care.”
• “Unfortunately, family policies and programs under President Biden’s HHS are fraught with agenda items focusing on ‘LGBTQ+ equity,’ subsidizing single motherhood, disincentivizing work, and penalizing marriage. These policies should be repealed and replaced by policies that support the formation of stable, married, nuclear families.”
• “The next Administration should guard against the regulatory capture of our public health agencies by pharmaceutical companies, insurers, hospital conglomerates, and related economic interests that these agencies are meant to regulate. We must erect robust firewalls to mitigate these obvious financial conflicts of interest.”
• “All National Institutes of Health, Centers for Disease Control and Prevention, and Food and Drug Administration regulators should be entirely free from private biopharmaceutical funding. In this realm, ‘public–private partnerships’ is a euphemism for agency capture, a thin veneer for corporatism. Funding for agencies and individual government researchers must come directly from the government with robust congressional oversight.”
• “The CDC [Centers for Disease Control and Prevention] operates several programs related to vaccine safety including the Vaccine Adverse Event Reporting System (VAERS); Vaccine Safety Datalink (VSD); and Clinical Immunization Safety Assessment (CISA) Project. Those functions and their associated funding should be transferred to the FDA [Food and Drug Administration], which is responsible for post-market surveillance and evaluation of all other drugs and biological products.”
• “Because liberal states have now become sanctuaries for abortion tourism, HHS should use every available tool, including the cutting of funds, to ensure that every state reports exactly how many abortions take place within its borders, at what gestational age of the child, for what reason, the mother’s state of residence, and by what method. It should also ensure that statistics are separated by category: spontaneous miscarriage; treatments that incidentally result in the death of a child (such as chemotherapy); stillbirths; and induced abortion. In addition, CDC should require monitoring and reporting for complications due to abortion and every instance of children being born alive after an abortion.”
• “The CDC should immediately end its collection of data on gender identity, which legitimizes the unscientific notion that men can become women (and vice versa) and encourages the phenomenon of ever-multiplying subjective identities.”
• “A test developed by a lab in accordance with the protocols developed by another lab (non-commercial sharing) currently constitutes a ‘new’ laboratory-developed test because the lab in which it will be used is different from the initial developing lab. To encourage interlaboratory collaboration and discourage duplicative test creation (and associated regulatory and logistical burdens), the FDA should introduce mechanisms through which laboratory-developed tests can easily be shared with other laboratories without the current regulatory burdens.”
• “[FDA should] Reverse its approval of chemical abortion drugs because the politicized approval process was illegal from the start. The FDA failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.”
• “[FDA should] Stop promoting or approving mail-order abortions in violation of long-standing federal laws that prohibit the mailing and interstate carriage of abortion drugs.”
• “[HHS should] Promptly restore the ethics advisory committee to oversee abortion-derived fetal tissue research, and Congress should prohibit such research altogether.”
• “[HHS should] End intramural research projects using tissue from aborted children within the NIH, which should end its human embryonic stem cell registry.”
• “Under Francis Collins, NIH became so focused on the #MeToo movement that it refused to sponsor scientific conferences unless there were a certain number of women panelists, which violates federal civil rights law against sex discrimination. This quota practice should be ended, and the NIH Office of Equity, Diversity, and Inclusion, which pushes such unlawful actions, should be abolished.”
• “Make Medicare Advantage [MA] the default enrollment option.”
• “[Legislation reforming legacy (non-MA) Medicare should] Repeal harmful health policies enacted under the Obama and Biden Administrations such as the Medicare Shared Savings Program and Inflation Reduction Act.”
• “…the next Administration should] Add work requirements and match Medicaid benefits to beneficiary needs. Because Medicaid serves a broad and diverse group of individuals, it should be flexible enough to accommodate different designs for different groups.”
• “The No Surprises Act should scrap the dispute resolution process in favor of a truth-in-advertising approach that will protect consumers and free doctors, insurers, and arbiters from confused and conflicting standards for resolving disputes that the disputing parties can best resolve themselves.”
• “Prohibit abortion travel funding. Providing funding for abortions increases the number of abortions and violates the conscience and religious freedom rights of Americans who object to subsidizing the taking of life.”
• “Prohibit Planned Parenthood from receiving Medicaid funds. During the 2020–2021 reporting period, Planned Parenthood performed more than 383,000 abortions.”
• “Protect faith-based grant recipients from religious liberty violations and maintain a biblically based, social science–reinforced definition of marriage and family. Social science reports that assess the objective outcomes for children raised in homes aside from a heterosexual, intact marriage are clear.”
• “Allocate funding to strategy programs promoting father involvement or terminate parental rights quickly.”
• “Eliminate the Head Start program.”
• “Support palliative care. Physician-assisted suicide (PAS) is legal in 10 states and the District of Columbia. Legalizing PAS is a grave mistake that endangers the weak and vulnerable, corrupts the practice of medicine and the doctor–patient relationship, compromises the family and intergenerational commitments, and betrays human dignity and equality before the law.”
• “Eliminate men’s preventive services from the women’s preventive services mandate. In December 2021, HRSA [Health Resources and Services Administration] updated its women’s preventive services guidelines to include male condoms.”
• “Prioritize funding for home-based childcare, not universal day care.”
• “ The Office of the Secretary should eliminate the HHS Reproductive Healthcare Access Task Force and install a pro-life task force to ensure that all of the department’s divisions seek to use their authority to promote the life and health of women and their unborn children.”
• “The ASH [Assistant Secretary for Health] and SG [Surgeon General] positions should be combined into one four-star position with the rank, responsibilities, and authority of the ASH retained but with the title of Surgeon General.”
• “OCR [Office for Civil Rights] should withdraw its Health Insurance Portability and Accountability Act (HIPAA) guidance on abortion.”

Dr. Lundberg is Editor in Chief, Cancer Commons, and has disclosed no relevant financial relationships.

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

TOPLINE:

A higher resting heart rate, even within the normal range, is linked to an increased risk for mortality and cardiovascular events in patients with non–dialysis-dependent chronic kidney disease (CKD).

METHODOLOGY:

• An elevated resting heart rate is an independent risk factor for all-cause mortality and cardiovascular events in the general population; however, the correlation between heart rate and mortality in patients with CKD is unclear.
• Researchers analyzed the longitudinal data of patients with non–dialysis-dependent CKD enrolled in the Fukushima CKD Cohort Study to investigate the association between resting heart rate and adverse clinical outcomes.
• The patient cohort was stratified into four groups on the basis of resting heart rates: < 70, 70-79, 80-89, and ≥ 90 beats/min.
• The primary and secondary outcomes were all-cause mortality and cardiovascular events, respectively, the latter category including myocardial infarction, angina pectoris, and heart failure.

TAKEAWAY:

• Researchers enrolled 1353 patients with non–dialysis-dependent CKD (median age, 65 years; 56.7% men; median estimated glomerular filtration rate, 52.2 mL/min/1.73 m²) who had a median heart rate of 76 beats/min.
• During the median observation period of 4.9 years, 123 patients died and 163 developed cardiovascular events.
• Compared with patients with a resting heart rate < 70 beats/min, those with a resting heart rate of 80-89 and ≥ 90 beats/min had an adjusted hazard ratio of 1.74 and 2.61 for all-cause mortality, respectively.
• Similarly, the risk for cardiovascular events was higher in patients with a heart rate of 80-89 beats/min than in those with a heart rate < 70 beats/min (adjusted hazard ratio, 1.70).

IN PRACTICE:

“The present study supported the idea that reducing heart rate might be effective for CKD patients with a heart rate ≥ 70/min, since the lowest risk of mortality was seen in patients with heart rate < 70/min,” the authors concluded. 

SOURCE:

This study was led by Hirotaka Saito, Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima City, Japan. It was published online in Scientific Reports.

LIMITATIONS:

Heart rate was measured using a standard sphygmomanometer or an automated device, rather than an electrocardiograph, which may have introduced measurement variability. The observational nature of the study precluded the establishment of cause-and-effect relationships between heart rate and clinical outcomes. Additionally, variables such as lifestyle factors, underlying health conditions, and socioeconomic factors were not measured, which could have affected the results. 

DISCLOSURES:

Some authors received research funding from Chugai Pharmaceutical, Kowa Pharmaceutical, Ono Pharmaceutical, and other sources. They declared having no competing interests.

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

TOPLINE:

A higher resting heart rate, even within the normal range, is linked to an increased risk for mortality and cardiovascular events in patients with non–dialysis-dependent chronic kidney disease (CKD).

METHODOLOGY:

• An elevated resting heart rate is an independent risk factor for all-cause mortality and cardiovascular events in the general population; however, the correlation between heart rate and mortality in patients with CKD is unclear.
• Researchers analyzed the longitudinal data of patients with non–dialysis-dependent CKD enrolled in the Fukushima CKD Cohort Study to investigate the association between resting heart rate and adverse clinical outcomes.
• The patient cohort was stratified into four groups on the basis of resting heart rates: < 70, 70-79, 80-89, and ≥ 90 beats/min.
• The primary and secondary outcomes were all-cause mortality and cardiovascular events, respectively, the latter category including myocardial infarction, angina pectoris, and heart failure.

TAKEAWAY:

• Researchers enrolled 1353 patients with non–dialysis-dependent CKD (median age, 65 years; 56.7% men; median estimated glomerular filtration rate, 52.2 mL/min/1.73 m²) who had a median heart rate of 76 beats/min.
• During the median observation period of 4.9 years, 123 patients died and 163 developed cardiovascular events.
• Compared with patients with a resting heart rate < 70 beats/min, those with a resting heart rate of 80-89 and ≥ 90 beats/min had an adjusted hazard ratio of 1.74 and 2.61 for all-cause mortality, respectively.
• Similarly, the risk for cardiovascular events was higher in patients with a heart rate of 80-89 beats/min than in those with a heart rate < 70 beats/min (adjusted hazard ratio, 1.70).

IN PRACTICE:

“The present study supported the idea that reducing heart rate might be effective for CKD patients with a heart rate ≥ 70/min, since the lowest risk of mortality was seen in patients with heart rate < 70/min,” the authors concluded. 

SOURCE:

This study was led by Hirotaka Saito, Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima City, Japan. It was published online in Scientific Reports.

LIMITATIONS:

Heart rate was measured using a standard sphygmomanometer or an automated device, rather than an electrocardiograph, which may have introduced measurement variability. The observational nature of the study precluded the establishment of cause-and-effect relationships between heart rate and clinical outcomes. Additionally, variables such as lifestyle factors, underlying health conditions, and socioeconomic factors were not measured, which could have affected the results. 

DISCLOSURES:

Some authors received research funding from Chugai Pharmaceutical, Kowa Pharmaceutical, Ono Pharmaceutical, and other sources. They declared having no competing interests.

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

TOPLINE:

A higher resting heart rate, even within the normal range, is linked to an increased risk for mortality and cardiovascular events in patients with non–dialysis-dependent chronic kidney disease (CKD).

METHODOLOGY:

• An elevated resting heart rate is an independent risk factor for all-cause mortality and cardiovascular events in the general population; however, the correlation between heart rate and mortality in patients with CKD is unclear.
• Researchers analyzed the longitudinal data of patients with non–dialysis-dependent CKD enrolled in the Fukushima CKD Cohort Study to investigate the association between resting heart rate and adverse clinical outcomes.
• The patient cohort was stratified into four groups on the basis of resting heart rates: < 70, 70-79, 80-89, and ≥ 90 beats/min.
• The primary and secondary outcomes were all-cause mortality and cardiovascular events, respectively, the latter category including myocardial infarction, angina pectoris, and heart failure.

TAKEAWAY:

• Researchers enrolled 1353 patients with non–dialysis-dependent CKD (median age, 65 years; 56.7% men; median estimated glomerular filtration rate, 52.2 mL/min/1.73 m²) who had a median heart rate of 76 beats/min.
• During the median observation period of 4.9 years, 123 patients died and 163 developed cardiovascular events.
• Compared with patients with a resting heart rate < 70 beats/min, those with a resting heart rate of 80-89 and ≥ 90 beats/min had an adjusted hazard ratio of 1.74 and 2.61 for all-cause mortality, respectively.
• Similarly, the risk for cardiovascular events was higher in patients with a heart rate of 80-89 beats/min than in those with a heart rate < 70 beats/min (adjusted hazard ratio, 1.70).

IN PRACTICE:

“The present study supported the idea that reducing heart rate might be effective for CKD patients with a heart rate ≥ 70/min, since the lowest risk of mortality was seen in patients with heart rate < 70/min,” the authors concluded. 

SOURCE:

This study was led by Hirotaka Saito, Department of Nephrology and Hypertension, Fukushima Medical University, Fukushima City, Japan. It was published online in Scientific Reports.

LIMITATIONS:

Heart rate was measured using a standard sphygmomanometer or an automated device, rather than an electrocardiograph, which may have introduced measurement variability. The observational nature of the study precluded the establishment of cause-and-effect relationships between heart rate and clinical outcomes. Additionally, variables such as lifestyle factors, underlying health conditions, and socioeconomic factors were not measured, which could have affected the results. 

DISCLOSURES:

Some authors received research funding from Chugai Pharmaceutical, Kowa Pharmaceutical, Ono Pharmaceutical, and other sources. They declared having no competing interests.

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

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

Rheumatoid arthritis (RA) disease activity and inflammatory markers are associated with major adverse cardiovascular events (MACEs) in biologic disease-modifying antirheumatic drug (bDMARD) nonusers but not in users, suggesting that biologics may reduce cardiovascular risk in RA even if remission is not achieved.

METHODOLOGY:

• Studies reported reduced cardiovascular risk in patients with RA who respond to tumor necrosis factor inhibitors but not in nonresponders, highlighting the importance of controlling inflammation for cardiovascular protection.
• Researchers assessed whether bDMARDs modify the impact of disease activity and systemic inflammation on cardiovascular risk in 4370 patients (mean age, 55 years) with RA without cardiovascular disease from a 10-country observational cohort.
• The severity of RA disease activity was assessed using C-reactive protein (CRP) levels and 28-joint Disease Activity Score based on CRP (DAS28-CRP).
• Endpoints were time to first MACE — a composite of cardiovascular death, myocardial infarction, and stroke — and time to first ischemic cardiovascular event (iCVE) — a composite of MACE plus revascularization, angina, transient ischemic attack, and peripheral arterial disease.

TAKEAWAY:

• The interaction between use of bDMARD and DAS28-CRP (P = .017) or CRP (P = .011) was significant for MACE.
• Each unit increase in DAS28-CRP increased the risk for MACE in bDMARD nonusers (hazard ratio [HR], 1.21; P = .002) but not in users.
• The per log unit increase in CRP was associated with a risk for MACE in bDMARD nonusers (HR, 1.16; P = .009) but not in users.
• No interaction was observed between bDMARD use and DAS28-CRP or CRP for the iCVE risk.

IN PRACTICE:

“This may indicate additional bDMARD-specific benefits directly on arterial wall inflammation and atherosclerotic plaque anatomy, stability, and biology, independently of systemic inflammation,” the authors wrote.

SOURCE:

The study, led by George Athanasios Karpouzas, MD, The Lundquist Institute, Torrance, California, was published online in RMD Open.

LIMITATIONS:

Patients with a particular interest in RA-associated cardiovascular disease were included, which may have introduced referral bias and affected the generalizability of the findings. Standard definitions were used for selected outcomes; however, differences in the reporting of outcomes may be plausible. Some patients were evaluated prospectively, while others were evaluated retrospectively, leading to differences in surveillance.

DISCLOSURES:

The study was supported by Pfizer. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

This transcript has been edited for clarity. 

Two individuals in the United States are celebrating their 30th birthdays. It’s a good day. They are entering the prime of their lives. One is a married White woman with a university degree. The other is a never-married White man with a high school diploma. 

How many more years of life can these two individuals look forward to? 

There’s a fairly dramatic difference. The man can expect 37.1 more years of life on average, living to be about 67. The woman can expect to live to age 85. That’s a life-expectancy discrepancy of 18 years based solely on gender, education, and marital status. 

I’m using these cases to illustrate the extremes of life expectancy across four key social determinants of health: sex, race, marital status, and education. We all have some sense of how these factors play out in terms of health, but a new study suggests that it’s actually quite a bit more complicated than we thought.

Let me start by acknowledging my own bias here. As a clinical researcher, I sometimes find it hard to appreciate the value of actuarial-type studies that look at life expectancy (or any metric, really) between groups defined by marital status, for example. I’m never quite sure what to do with the conclusion. Married people live longer, the headline says. Okay, but as a doctor, what am I supposed to do about that? Encourage my patients to settle down and commit? Studies showing that women live longer than men or that White people live longer than Black people are also hard for me to incorporate into my practice. These are not easily changeable states. My time is better spent getting people to quit smoking or eat healthier or touch grass or something.

But studies examining these groups are a reasonable starting point to ask more relevant questions. Why do women live longer than men? Is it behavioral (men take more risks and are less likely to see doctors)? Or is it hormonal (estrogen has a lot of protective effects that testosterone does not)? Or is it something else?

Integrating these social determinants of health into a cohesive story is a bit harder than it might seem, as this study, appearing in BMJ Open, illustrates.

In the context of this study, every person in America can be placed into one of 54 mutually exclusive groups. You can be male or female. You can be Black, White, or Hispanic. You can have a high school diploma or less, an associate degree, or a college degree; and you can be married, previously married, or never married. 

BMJ Open

BMJ Open

BMJ Open

BMJ Open

Dr. Wilson is associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator, New Haven, Connecticut. He has disclosed no relevant financial relationships.

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

This transcript has been edited for clarity. 

Two individuals in the United States are celebrating their 30th birthdays. It’s a good day. They are entering the prime of their lives. One is a married White woman with a university degree. The other is a never-married White man with a high school diploma. 

How many more years of life can these two individuals look forward to? 

There’s a fairly dramatic difference. The man can expect 37.1 more years of life on average, living to be about 67. The woman can expect to live to age 85. That’s a life-expectancy discrepancy of 18 years based solely on gender, education, and marital status. 

I’m using these cases to illustrate the extremes of life expectancy across four key social determinants of health: sex, race, marital status, and education. We all have some sense of how these factors play out in terms of health, but a new study suggests that it’s actually quite a bit more complicated than we thought.

Let me start by acknowledging my own bias here. As a clinical researcher, I sometimes find it hard to appreciate the value of actuarial-type studies that look at life expectancy (or any metric, really) between groups defined by marital status, for example. I’m never quite sure what to do with the conclusion. Married people live longer, the headline says. Okay, but as a doctor, what am I supposed to do about that? Encourage my patients to settle down and commit? Studies showing that women live longer than men or that White people live longer than Black people are also hard for me to incorporate into my practice. These are not easily changeable states. My time is better spent getting people to quit smoking or eat healthier or touch grass or something.

But studies examining these groups are a reasonable starting point to ask more relevant questions. Why do women live longer than men? Is it behavioral (men take more risks and are less likely to see doctors)? Or is it hormonal (estrogen has a lot of protective effects that testosterone does not)? Or is it something else?

Integrating these social determinants of health into a cohesive story is a bit harder than it might seem, as this study, appearing in BMJ Open, illustrates.

In the context of this study, every person in America can be placed into one of 54 mutually exclusive groups. You can be male or female. You can be Black, White, or Hispanic. You can have a high school diploma or less, an associate degree, or a college degree; and you can be married, previously married, or never married. 

BMJ Open

BMJ Open

BMJ Open

BMJ Open

Dr. Wilson is associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator, New Haven, Connecticut. He has disclosed no relevant financial relationships.

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

This transcript has been edited for clarity. 

Two individuals in the United States are celebrating their 30th birthdays. It’s a good day. They are entering the prime of their lives. One is a married White woman with a university degree. The other is a never-married White man with a high school diploma. 

How many more years of life can these two individuals look forward to? 

There’s a fairly dramatic difference. The man can expect 37.1 more years of life on average, living to be about 67. The woman can expect to live to age 85. That’s a life-expectancy discrepancy of 18 years based solely on gender, education, and marital status. 

I’m using these cases to illustrate the extremes of life expectancy across four key social determinants of health: sex, race, marital status, and education. We all have some sense of how these factors play out in terms of health, but a new study suggests that it’s actually quite a bit more complicated than we thought.

Let me start by acknowledging my own bias here. As a clinical researcher, I sometimes find it hard to appreciate the value of actuarial-type studies that look at life expectancy (or any metric, really) between groups defined by marital status, for example. I’m never quite sure what to do with the conclusion. Married people live longer, the headline says. Okay, but as a doctor, what am I supposed to do about that? Encourage my patients to settle down and commit? Studies showing that women live longer than men or that White people live longer than Black people are also hard for me to incorporate into my practice. These are not easily changeable states. My time is better spent getting people to quit smoking or eat healthier or touch grass or something.

But studies examining these groups are a reasonable starting point to ask more relevant questions. Why do women live longer than men? Is it behavioral (men take more risks and are less likely to see doctors)? Or is it hormonal (estrogen has a lot of protective effects that testosterone does not)? Or is it something else?

Integrating these social determinants of health into a cohesive story is a bit harder than it might seem, as this study, appearing in BMJ Open, illustrates.

In the context of this study, every person in America can be placed into one of 54 mutually exclusive groups. You can be male or female. You can be Black, White, or Hispanic. You can have a high school diploma or less, an associate degree, or a college degree; and you can be married, previously married, or never married. 

BMJ Open

BMJ Open

BMJ Open

BMJ Open

Dr. Wilson is associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator, New Haven, Connecticut. He has disclosed no relevant financial relationships.

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

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

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

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

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

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

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

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

Is going sugar free really good advice for patients with cardiometabolic risk factors? 

That’s the question raised by new Cleveland Clinic research, which suggests that consuming erythritol, a sweetener widely found in sugar-free and keto food products, could spur a prothrombotic response. 

In the study, published in Arteriosclerosis, Thrombosis, and Vascular Biology, 10 healthy participants ate 30 grams of erythritol. Thirty minutes later, their blood showed enhanced platelet aggregation and increased markers of platelet responsiveness and activation. 

Specifically, the researchers saw enhanced stimulus-dependent release of serotonin (a marker of platelet dense granules) and CXCL4 (a platelet alpha-granule marker). 

“ With every single person, you see a prothrombotic effect with every single test that we did,” said study author Stanley Hazen, MD, PhD, chair of the Department of Cardiovascular & Metabolic Sciences at Cleveland Clinic in Ohio. By contrast, participants who ate 30 grams of glucose saw no such effect. 

The erythritol itself does not activate the platelets, Dr. Hazen said, rather it lowers the threshold for triggering a response. This could make someone more prone to clotting, raising heart attack and stroke risk over time.

Though the mechanism is unknown, Dr. Hazen has an idea. 

“There appears to be a receptor on platelets that is recognizing and sensing these sugar alcohols,” Dr. Hazen said, “much in the same way your taste bud for sweet is a receptor for recognizing a glucose or sugar molecule.” 

“We’re very interested in trying to figure out what the receptor is,” Dr. Hazen said, “because I think that then becomes a very interesting potential target for further investigation and study into how this is linked to causing heart disease.”
 

The Past and Future of Erythritol Research

In 2001, the Food and Drug Administration classified erythritol as a “generally recognized as safe” food additive. A sugar alcohol that occurs naturally in foods like melon and grapes, erythritol is also manufactured by fermenting sugars. It’s about 70% as sweet as table sugar. Humans also produce small amounts of erythritol naturally: Our blood cells make it from glucose via the pentose phosphate pathway. 

Previous research from Dr. Hazen’s group linked erythritol to a risk for major adverse cardiovascular events and clotting. 

“Based on their previous study, I think this was a really important study to do in healthy individuals,” said Martha Field, PhD, assistant professor in the Division of Nutritional Sciences at Cornell University, Ithaca, New York, who was not involved in the study.

The earlier paper analyzed blood samples from participants with unknown erythritol intake, including some taken before the sweetener, and it was as widespread as it is today. That made disentangling the effects of eating erythritol vs naturally producing it more difficult. 

By showing that eating erythritol raises markers associated with thrombosis, the new paper reinforces the importance of thinking about and developing a deeper understanding of what we put into our bodies. 

“This paper was conducted in healthy individuals — might this be particularly dangerous for individuals who are at increased risk of clotting?” asked Dr. Field. “There are lots of genetic polymorphisms that increase your risk for clotting disorders or your propensity to form thrombosis.” 

Field would like to see similar analyses of xylitol and sorbitol, other sugar alcohols found in sugar-free foods. And she called for more studies on erythritol that look at lower erythritol consumption over longer time periods. 

Registered dietitian nutritionist Valisa E. Hedrick, PhD, agreed: Much more work is needed in this area, particularly in higher-risk groups, such as those with prediabetes and diabetes, said Dr. Hedrick, an associate professor in the Department of Human Nutrition, Foods, and Exercise at Virginia Tech, Blacksburg, who was not involved in the study. 

“Because this study was conducted in healthy individuals, the impact of a small dose of glucose was negligible, as their body can effectively regulate blood glucose levels,” she said. “Because high blood glucose concentrations have also been shown to increase platelet reactivity, and consequently increase thrombosis potential, individuals who are not able to regulate their blood glucose levels, such as those with prediabetes and diabetes, could potentially see a similar effect on the body as erythritol when consuming large amounts of sugar.” 

At the same time, “individuals with diabetes or prediabetes may be more inclined to consume erythritol as an alternative to sugar,” Dr. Hedrick added. “It will be important to design studies that include these individuals to determine if erythritol has an additive adverse effect on cardiac event risk.”
 

Criticism and Impact 

Critics have suggested the 30-gram dose of erythritol ingested by study participants is unrealistic. Dr. Hazen said that it’s not. 

Erythritol is often recommended as a one-to-one sugar replacement. And you could top 30 grams with a few servings of erythritol-sweetened ice cream or soda, Dr. Hazen said. 

“The dose that we used, it’s on the high end, but it’s well within a physiologically relevant level,” he said. 

Still others say the results are only relevant for people with preexisting heart trouble. But Dr. Hazen said they matter for the masses. 

“I think there’s a significant health concern at a population level that this work is underscoring,” he said. 

After all, heart disease risk factors like obesity, hypertension, diabetes, and smoking are common and quickly add up. 

“If you look at middle-aged America, most people who experience a heart attack or stroke do not know that they have coronary artery disease, and the first recognition of it is that event,” Dr. Hazen said. 

For now, Dr. Hazen recommends eating real sugar in moderation. He hopes future research will reveal a nonnutritive sweetener that doesn’t activate platelets. 
 

The Bigger Picture

The new research adds yet another piece to the puzzle of whether nonnutritive sweeteners are better than sugar. 

“I think these results are concerning,” said JoAnn E. Manson, MD, chief of the Division of Preventive Medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts. They “ may help explain the surprising results in some observational studies that artificial sweeteners are linked to an increased risk of cardiovascular disease.”

Dr. Manson, who was not involved in the new study, has conducted other research linking artificial sweetener use with stroke risk.

In an upcoming randomized clinical study, her team is comparing head-to-head sugar-sweetened beverages, drinks sweetened with calorie-free substitutes, and water to determine which is best for a range of cardiometabolic outcomes. 

“We need more research on this question,” she said, “because these artificial sweeteners are commonly used, and many people are assuming that their health outcomes will be better with the artificial sweeteners than with sugar-sweetened products.”

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

The new American Heart Association Predicting Risk of cardiovascular disease EVENTs (PREVENT) equation outperforms the standard pooled cohort equation (PCE). But there is a problem. A big one, actually. 

The new score incorporates kidney function and social situation, and it eliminates race from the estimate. It was derived from larger, more modern datasets and can be applied to younger adults. 

Two luminaries in preventive cardiology recently called the PREVENT calculator a “substantial improvement over the PCE in terms of accuracy and precision of risk estimates over the entire population and within demographic subgroups.”
 

Now to the Problem of PREVENT vs PCE

A recent study comparing PREVENT and PCE found that the PREVENT equation would assign lower 10-year risks to millions of US adults. 

The authors estimated that the more accurate calculator would result in an estimated 14 million adults no longer reaching the statin eligibility risk threshold of 7.5% over 10 years. Nearly 3 million adults would also not reach the threshold for blood pressure therapy. 

Because statins and blood pressure drugs reduce cardiac events, the authors further estimated that more than 100,000 excess myocardial infarctions (MIs) would occur if the PREVENT equation was used along with the current risk thresholds for statin eligibility.

The change in eligibility induced by PREVENT would affect more men than women and a greater proportion of Black adults than White adults. 
 

The Tension of Arbitrary Thresholds

Modern cardiac therapeutics are amazing, but it’s still better to prevent an event than to treat it. 

Statin drugs reduce cardiac risk by about 20%-25% at all absolute risks. American experts chose a 10-year risk of 7.5% as the threshold where statin benefit exceed risk. The USPSTF chose 10%. But the thresholds are arbitrary and derived only by opinion. 

If your frame is population health, the more patients who take statins, the fewer cardiac events there will be. Anything that reduces statin use increases cardiac events. 

The tension occurs because a more accurate equation decreases the number of people who meet eligibility for primary prevention therapy and therefore increases the number of cardiac events. 

I write from the perspective of both a clinician and a possible patient. As a clinician, patients often ask me whether they should take a statin. (Sadly, most have not had a risk-based discussion with their clinician. But that is another column.) 

The incidence of MI or stroke in a population has no effect on either of these scenarios. I see three broad categories of patients: minimizers, maximizers, and those in between. 

I am a minimizer. I don’t worry much about heart disease. First, I won’t ignore symptoms, and I know that we have great treatments. Second, my wife, Staci, practiced hospice and palliative care medicine, and this taught me that worrying about one specific disease is folly. In the next decade, I, like anyone my age, could have many other bad things happen: cancer, trauma, infection, etc. Given these competing risks for serious disease, a PREVENT-calculated risk of 4% or a PCE-calculated risk of 8% makes no difference. I don’t like pills, and, with risks in this range, I decline statin drugs. 

Then there are the maximizers. This person wants to avoid heart disease. Maybe they have family or friends who had terrible cardiac events. This person will maximize everything to avoid heart disease. The calculated 10-year risk makes little difference to a maximizer. Whether it is 4% or 8% matters not. They will take a statin or blood pressure drugs to reduce risk to as low as possible. 

There are people between minimizers and maximizers. I am not sure that there are that many truly undecided people, but I challenge you to translate a difference of a few percent over a decade to them. I feel comfortable with numbers but struggle to sort out these small absolute differences over such a long time frame. 
 

Other Issues With Risk-Based Decisions 

Venk Murthy, MD, PhD, from the University of Michigan, wrote on X about two other issues with a risk-based decision. One is that it does not consider life-years lost. If a 50-year-old person has a fatal MI, that counts as one event. But in life-years lost, that one event is much worse than a fatal MI in a 79-year-old. Cardiac prevention, therefore, may have a greater effect in lower-risk younger people. 

Another point Dr. Murthy made is that risk and benefit are driven by many different preferences and rare events. Minimizers and maximizers come to the decision with widely disparate preferences. Risk-based decisions treat patients as if they were automatons who make decisions based simply on calculated probabilities. Clinicians know how untrue that is. 
 

Conclusion

If you carry forward the logic of being disturbed by the estimate of more MIs using the PREVENT score, then you could justify putting statins in the water — because that would reduce population estimates of MIs. 

I am not disturbed by the PREVENT score. Clinicians treat individuals, not populations. Individuals want a more accurate score. They don’t need expert-based thresholds. Clinician and patient can discuss the evidence and come up with an agreeable decision, one that is concordant with a person’s goals. The next patient may have a different decision despite seeing the same evidence. 

The tension created by this comparative study exposes the gap between population health and basic clinical care. I don’t think clinicians need to worry about populations. 
 

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

A version of this article appeared on Medscape.com.

The new American Heart Association Predicting Risk of cardiovascular disease EVENTs (PREVENT) equation outperforms the standard pooled cohort equation (PCE). But there is a problem. A big one, actually. 

The new score incorporates kidney function and social situation, and it eliminates race from the estimate. It was derived from larger, more modern datasets and can be applied to younger adults. 

Two luminaries in preventive cardiology recently called the PREVENT calculator a “substantial improvement over the PCE in terms of accuracy and precision of risk estimates over the entire population and within demographic subgroups.”
 

Now to the Problem of PREVENT vs PCE

A recent study comparing PREVENT and PCE found that the PREVENT equation would assign lower 10-year risks to millions of US adults. 

The authors estimated that the more accurate calculator would result in an estimated 14 million adults no longer reaching the statin eligibility risk threshold of 7.5% over 10 years. Nearly 3 million adults would also not reach the threshold for blood pressure therapy. 

Because statins and blood pressure drugs reduce cardiac events, the authors further estimated that more than 100,000 excess myocardial infarctions (MIs) would occur if the PREVENT equation was used along with the current risk thresholds for statin eligibility.

The change in eligibility induced by PREVENT would affect more men than women and a greater proportion of Black adults than White adults. 
 

The Tension of Arbitrary Thresholds

Modern cardiac therapeutics are amazing, but it’s still better to prevent an event than to treat it. 

Statin drugs reduce cardiac risk by about 20%-25% at all absolute risks. American experts chose a 10-year risk of 7.5% as the threshold where statin benefit exceed risk. The USPSTF chose 10%. But the thresholds are arbitrary and derived only by opinion. 

If your frame is population health, the more patients who take statins, the fewer cardiac events there will be. Anything that reduces statin use increases cardiac events. 

The tension occurs because a more accurate equation decreases the number of people who meet eligibility for primary prevention therapy and therefore increases the number of cardiac events. 

I write from the perspective of both a clinician and a possible patient. As a clinician, patients often ask me whether they should take a statin. (Sadly, most have not had a risk-based discussion with their clinician. But that is another column.) 

The incidence of MI or stroke in a population has no effect on either of these scenarios. I see three broad categories of patients: minimizers, maximizers, and those in between. 

I am a minimizer. I don’t worry much about heart disease. First, I won’t ignore symptoms, and I know that we have great treatments. Second, my wife, Staci, practiced hospice and palliative care medicine, and this taught me that worrying about one specific disease is folly. In the next decade, I, like anyone my age, could have many other bad things happen: cancer, trauma, infection, etc. Given these competing risks for serious disease, a PREVENT-calculated risk of 4% or a PCE-calculated risk of 8% makes no difference. I don’t like pills, and, with risks in this range, I decline statin drugs. 

Then there are the maximizers. This person wants to avoid heart disease. Maybe they have family or friends who had terrible cardiac events. This person will maximize everything to avoid heart disease. The calculated 10-year risk makes little difference to a maximizer. Whether it is 4% or 8% matters not. They will take a statin or blood pressure drugs to reduce risk to as low as possible. 

There are people between minimizers and maximizers. I am not sure that there are that many truly undecided people, but I challenge you to translate a difference of a few percent over a decade to them. I feel comfortable with numbers but struggle to sort out these small absolute differences over such a long time frame. 
 

Other Issues With Risk-Based Decisions 

Venk Murthy, MD, PhD, from the University of Michigan, wrote on X about two other issues with a risk-based decision. One is that it does not consider life-years lost. If a 50-year-old person has a fatal MI, that counts as one event. But in life-years lost, that one event is much worse than a fatal MI in a 79-year-old. Cardiac prevention, therefore, may have a greater effect in lower-risk younger people. 

Another point Dr. Murthy made is that risk and benefit are driven by many different preferences and rare events. Minimizers and maximizers come to the decision with widely disparate preferences. Risk-based decisions treat patients as if they were automatons who make decisions based simply on calculated probabilities. Clinicians know how untrue that is. 
 

Conclusion

If you carry forward the logic of being disturbed by the estimate of more MIs using the PREVENT score, then you could justify putting statins in the water — because that would reduce population estimates of MIs. 

I am not disturbed by the PREVENT score. Clinicians treat individuals, not populations. Individuals want a more accurate score. They don’t need expert-based thresholds. Clinician and patient can discuss the evidence and come up with an agreeable decision, one that is concordant with a person’s goals. The next patient may have a different decision despite seeing the same evidence. 

The tension created by this comparative study exposes the gap between population health and basic clinical care. I don’t think clinicians need to worry about populations. 
 

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

A version of this article appeared on Medscape.com.

The new American Heart Association Predicting Risk of cardiovascular disease EVENTs (PREVENT) equation outperforms the standard pooled cohort equation (PCE). But there is a problem. A big one, actually. 

The new score incorporates kidney function and social situation, and it eliminates race from the estimate. It was derived from larger, more modern datasets and can be applied to younger adults. 

Two luminaries in preventive cardiology recently called the PREVENT calculator a “substantial improvement over the PCE in terms of accuracy and precision of risk estimates over the entire population and within demographic subgroups.”
 

Now to the Problem of PREVENT vs PCE

A recent study comparing PREVENT and PCE found that the PREVENT equation would assign lower 10-year risks to millions of US adults. 

The authors estimated that the more accurate calculator would result in an estimated 14 million adults no longer reaching the statin eligibility risk threshold of 7.5% over 10 years. Nearly 3 million adults would also not reach the threshold for blood pressure therapy. 

Because statins and blood pressure drugs reduce cardiac events, the authors further estimated that more than 100,000 excess myocardial infarctions (MIs) would occur if the PREVENT equation was used along with the current risk thresholds for statin eligibility.

The change in eligibility induced by PREVENT would affect more men than women and a greater proportion of Black adults than White adults. 
 

The Tension of Arbitrary Thresholds

Modern cardiac therapeutics are amazing, but it’s still better to prevent an event than to treat it. 

Statin drugs reduce cardiac risk by about 20%-25% at all absolute risks. American experts chose a 10-year risk of 7.5% as the threshold where statin benefit exceed risk. The USPSTF chose 10%. But the thresholds are arbitrary and derived only by opinion. 

If your frame is population health, the more patients who take statins, the fewer cardiac events there will be. Anything that reduces statin use increases cardiac events. 

The tension occurs because a more accurate equation decreases the number of people who meet eligibility for primary prevention therapy and therefore increases the number of cardiac events. 

I write from the perspective of both a clinician and a possible patient. As a clinician, patients often ask me whether they should take a statin. (Sadly, most have not had a risk-based discussion with their clinician. But that is another column.) 

The incidence of MI or stroke in a population has no effect on either of these scenarios. I see three broad categories of patients: minimizers, maximizers, and those in between. 

I am a minimizer. I don’t worry much about heart disease. First, I won’t ignore symptoms, and I know that we have great treatments. Second, my wife, Staci, practiced hospice and palliative care medicine, and this taught me that worrying about one specific disease is folly. In the next decade, I, like anyone my age, could have many other bad things happen: cancer, trauma, infection, etc. Given these competing risks for serious disease, a PREVENT-calculated risk of 4% or a PCE-calculated risk of 8% makes no difference. I don’t like pills, and, with risks in this range, I decline statin drugs. 

Then there are the maximizers. This person wants to avoid heart disease. Maybe they have family or friends who had terrible cardiac events. This person will maximize everything to avoid heart disease. The calculated 10-year risk makes little difference to a maximizer. Whether it is 4% or 8% matters not. They will take a statin or blood pressure drugs to reduce risk to as low as possible. 

There are people between minimizers and maximizers. I am not sure that there are that many truly undecided people, but I challenge you to translate a difference of a few percent over a decade to them. I feel comfortable with numbers but struggle to sort out these small absolute differences over such a long time frame. 
 

Other Issues With Risk-Based Decisions 

Venk Murthy, MD, PhD, from the University of Michigan, wrote on X about two other issues with a risk-based decision. One is that it does not consider life-years lost. If a 50-year-old person has a fatal MI, that counts as one event. But in life-years lost, that one event is much worse than a fatal MI in a 79-year-old. Cardiac prevention, therefore, may have a greater effect in lower-risk younger people. 

Another point Dr. Murthy made is that risk and benefit are driven by many different preferences and rare events. Minimizers and maximizers come to the decision with widely disparate preferences. Risk-based decisions treat patients as if they were automatons who make decisions based simply on calculated probabilities. Clinicians know how untrue that is. 
 

Conclusion

If you carry forward the logic of being disturbed by the estimate of more MIs using the PREVENT score, then you could justify putting statins in the water — because that would reduce population estimates of MIs. 

I am not disturbed by the PREVENT score. Clinicians treat individuals, not populations. Individuals want a more accurate score. They don’t need expert-based thresholds. Clinician and patient can discuss the evidence and come up with an agreeable decision, one that is concordant with a person’s goals. The next patient may have a different decision despite seeing the same evidence. 

The tension created by this comparative study exposes the gap between population health and basic clinical care. I don’t think clinicians need to worry about populations. 
 

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

A version of this article appeared on Medscape.com.