MDedge Cardiology

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

A recent series of columns on practice merger options generated a multitude of questions regarding merger, employment, and buyout agreements. The most common question was, “Do I really need to go to the trouble and expense of negotiating them?” If you have more than one physician in your group, you absolutely do need written contracts for a variety of reasons, but mostly to avoid conflicts later on. The proverbial “handshake agreement” is worthless in a major business dispute; everyone loses in such situations except the lawyers and accountants.

Mergers and buy-ins were covered at some length in my two previous columns. If the arrangement is to be one of employer and employees rather than a merger of equal partners, you will need an employment agreement to cover duties, requirements, expectations, and benefits. They define how each practitioner/employee will be paid, along with paid time off, health insurance, expense allowances, and malpractice coverage, among other basics. The more that is spelled out in the employment agreement, the fewer disagreements you are likely to have down the road.

Many employment contracts include a “termination without cause” clause, which benefits both the practice and the practitioners. It allows a practice to terminate a new associate if it feels a mistake has been made, even if he or she has done nothing wrong. On the other hand, the newcomer has the option to terminate if a better offer arises, their spouse hates the area, or for any other reason.

Buyouts should be addressed in advance as well. Several recent correspondents told me they didn’t see the necessity of writing a buyout agreement, because they plan to eventually sell their practice, rendering any buyout conditions moot. But what happens if an associate dies, becomes permanently disabled, or abruptly decides to leave the practice? If you haven’t prepared for such eventualities, you could find yourself receiving a demand from your ex-partner (or surviving spouse) for immediate payment of that partner’s portion of the practice’s value. And your valuation of the practice is likely to be severely at odds with the other party’s. Meanwhile, remaining partners must cover all the practice’s expenses and deal with an increased patient load.

A buyout agreement avoids these problems by planning for such eventualities in advance. You must agree on how a buyout amount will be valued. As I’ve said in previous columns, I strongly advise using a formula, not a fixed amount. If a buyout is based on 15- or 20-year-old reimbursements, the buyout will have no relationship to what the partners are currently being paid. Likewise, any buyout calculated at “appraised value” is a problem, because the buyout amount remains a mystery until an appraisal is performed. If the appraised value ends up being too high, the remaining owners may refuse to pay it. Have an actuary create a formula, so that a buyout figure can be calculated at any time. This area, especially, is where you need experienced, competent legal advice.

To avoid surprises, any buyout should require ample notice (6-12 months is common) to allow time to rearrange finances and recruit a new provider. Vesting schedules, similar to those used in retirement plans, are also popular. If a partner leaves before a prescribed time period has elapsed – say, 20 years – the buyout is proportionally reduced.

Buyouts can also be useful when dealing with noncompete agreements, which are notoriously difficult (and expensive) to enforce. One solution is a buyout penalty; a departing partner can compete with his or her former practice, but at the cost of a substantially reduced buyout. This permits competition, but discourages it, and compensates the targeted practice.

Buyouts are also a potential solution to some buy-in issues. A new associate entering an established practice may not be able to contribute assets equal to existing partners’ stakes and may lack the cash necessary to make up the difference. One alternative is to agree that any inequalities will be compensated at the other end in buyout value. Those partners contributing more assets will receive larger buyouts than those contributing less.

As I’ve said many times, these are not negotiations to undertake on your own. Enlist the aid of a consultant or attorney (or both) with ample medical practice experience.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

Experts engaged in a contentious debate on the usefulness of the NOVA system, which divides foods into different categories based on how much they have been processed, during a session at a virtual conference sponsored by the American Society for Nutrition.

The NOVA system divides foods into “fresh or minimally processed,” such as strawberries or steel-cut oats; “processed culinary ingredients,” such as olive oil; “processed foods,” such as cheeses; and “ultra-processed foods.” UPFs are defined as “industrial formulations made by deconstructing natural food into its chemical constituents, modifying them and recombining them with additives into products liable to displace all other NOVA food groups.”

According to doctors who presented during the meeting, ultra-processed foods are drawing increased attention, because researchers have been examining them in National Institutes of Health–funded studies and journalists have been writing about them.

During the debate session at the meeting, some experts said that, with obesity and poor health skyrocketing, increased awareness and labeling of UPFs can only be a good thing. In contrast others noted at the meeting that the classification system that has come to be used for identifying UPFs – the NOVA Food Classification system – is too mushy, confusing, and, ultimately unhelpful.

Carlos Monteiro, MD, PhD, professor of nutrition and public health at the University of Sao Paolo, was part of the group favoring the NOVA system’s classifying certain foods as UPFs, during the debate. He drew attention to the extent to which the world’s population is getting its calories from UPFs.

Mexico and France get about 30% of calories from these foods. In Canada, it’s 48%. And in the United States, it’s 57%, Dr. Monteiro said.

Studies have found that UPFs, many of which are designed to be exceedingly flavorful and intended to replace consumption of unprocessed whole foods, lead to more overall energy intake, more added sugar in the diet, and less fiber and protein intake, he said.

To further support his arguments, Dr. Monteiro pointed to studies suggesting that it is not just the resulting change in the nutritional intake that is unhealthy, but the UPF manufacturing process itself. When adjusting for fat, sugar, and sodium intake, for example, health outcomes associated with UPFs remain poor, he explained.

“I’m sorry,” he said in the debate. “If you don’t reduce this, you don’t reduce your obesity, your diabetes prevalence.”

A study presented by Jacqueline Vernarelli, PhD, during a different session at the meeting suggested there may be other downsides to consuming UPFs. This research, which was based on the U.S. National Youth Fitness Survey, found that poorer locomotor skills among children aged 3-5 and poorer cardiovascular fitness among those aged 12-15 were associated with getting more calories from UPFs.

Those with lower cardiovascular fitness consumed 1,234 calories a day from UPFs, and those with higher cardiovascular fitness consumed 1,007 calories a day from UPFs (P = .002), according to the new research.

“It’s notable here that, although these differences are significant, both groups are consuming a pretty high proportion of their diet from ultra-processed foods,” said Dr. Vernarelli, associate professor of public health at Sacred Heart University, Fairfield, Conn., during her presentation.

In the debate session, Arne Astrup, MD, PhD, senior project director at the Healthy Weight Center at the Novo Nordisk Foundation, Hellerup, Denmark, presented an opposing view.

He said the definition of UPFs makes it too difficult to categorize many foods, pointing to a study from this year in which about 150 nutrition experts, doctors, and dietitians classified 120 foods. Only three marketed foods and one generic food were classified the same by all the evaluators.

Referring to the study Dr. Astrup cited, Dr. Monteiro said it was a mere “exercise,” and the experts involved in it had conflicts of interest.

Dr. Astrup touted this study’s size and its appearance in the peer-reviewed journal the European Journal of Clinical Nutrition.

Defending his point of view, Dr. Astrup said, “The definition and classification is so ambiguous, and the risk of misclassification is so extremely high, I think we really miss the basic requirement of science, namely that we know what we are talking about,” he said.

If you take an unprocessed food, and insert a “little additive … suddenly it’s an ultra-processed food,” he added.
 

UPF definition doesn’t flag some unhealthy foods

Susan Roberts, PhD, professor of nutrition at Tufts University, Boston, was a discussant at the debate and touched on the merits of both sides. She noted that the UPF definition doesn’t flag some “clearly unhealthy foods,” such as table sugar, but does flag some healthy ones, such as plant-based burgers – to which Dr. Monteiro said that the system was not a system meant to divide foods into healthy and unhealthy groups, during the debate session.

The inclusion of both healthy and unhealthy foods in NOVA’s definition of a UPF is a serious problem, Dr. Roberts said.

“It’s almost like it’s an emotional classification designed to get at the food industry rather than focusing on health – and I think that’s asking for trouble because it’s just going to be such a mess to tell consumers, ‘Well, this ultra-processed food is healthy and this one isn’t,’ ” she said. What’s happening is the term ultra-processed is being used interchangeably with unhealthy.

The discussion that the UPF classification has generated is useful, Dr. Roberts continued. “This definition grew out of that recognition that we’re engaged in an unprecedented experiment of how unhealthy can you make the world without having a major catastrophe.”

She added that the UPF concept deserves a more formalized and rigorous evaluation.

“This is an important topic for the future of public health, and I think it needs big committees to address it seriously,” she said. “I think we should not be dealing with this individually in different labs.”
 

Doctor’s take on usefulness of discussing UPF concept with patients

Mark Corkins, MD, who did not participate in the debate at the meeting, said he talks to parents and children about nutrition at every office visit in which he sees a child with an unhealthy weight.

“Persistence wears down resistance,” said the chair of the American Academy of Pediatrics nutrition committee, in an interview.“A consistent message – you say the same thing and you say it multiple times.”

The idea of “ultra-processed foods” plays a role in those conversations, but largely in the background. It’s a topic that’s important for pediatric health, Dr. Corkins said – but he doesn’t make it the focal point.

“It’s not a direct attack on ultra-processed foods that usually I take as my direction,” said Dr. Corkins, who is also chief of pediatric gastroenterology at Le Bonheur Children’s Hospital in Memphis, Tenn.. “What I try to focus on, and what I think the American Academy of Pediatrics would focus on, is that we need to focus on making the diet better.”

He added, “Parents are aware – they don’t call it ultra-processed food, they call it junk food.”

Dr. Corkins continued that he is reluctant to directly challenge parents on feeding their children unhealthy foods – ultra-processed or not – lest he shame them and harm the relationship.

“Guilt as a motivator isn’t really highly successful,” he said, in an interview.

Dr. Astrup reported advisory committee or board member involvement with Green Leaf Medical and RNPC, France. Dr. Roberts reported advisory committee or board member involvement with Danone, and an ownership interest in Instinct Health Science. Dr. Monteiro and Dr. Corkins reported no relevant disclosures.

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

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

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

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

ATLANTA – U.S. clinicians caring for people with diabetes should take a more aggressive approach to using combined medical treatments proven to slow the otherwise relentless progression of chronic kidney disease (CKD), according to a new joint statement by the American Diabetes Association and a major international nephrology organization presented during the annual scientific sessions of the American Diabetes Association (ADA).

The statement elevates treatment with an agent from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class to first-line for people with diabetes and laboratory-based evidence of advancing CKD. It also re-emphasizes the key role of concurrent first-line treatment with a renin-angiotensin system inhibitor (an ACE inhibitor or angiotensin-receptor blocker), metformin, and a statin.

The new statement also urges clinicians to rapidly add treatment with the new nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia) for further renal protection in the many patients suitable for treatment with this agent, and it recommends the second-line addition of a glucagon-like peptide-1 (GLP-1) receptor agonist as the best add-on for any patient who needs additional glycemic control on top of metformin and an SGLT2 inhibitor.

The consensus joint statement with these updates came from a nine-member writing group assembled by the ADA and the Kidney Disease: Improving Global Outcomes (KDIGO) organization.

“We’re going to try to make this feasible. We have to; I don’t think we have a choice,” commented Amy K. Mottl, MD, a nephrologist at the University of North Carolina, Chapel Hill. Dr. Mottl was not involved with writing the consensus statement but has been active in the Diabetic Kidney Disease Collaborative of the American Society of Nephrology, another group promoting a more aggressive multidrug-class approach to treating CKD in people with diabetes.
 

Wider use of costly drugs

Adoption of this evidence-based approach by U.S. clinicians will both increase the number of agents that many patients receive and drive a significant uptick in the cost and complexity of patient care, a consequence acknowledged by the authors of the joint statement as well as outside experts.

But they view this as unavoidable given what’s now known about the high incidence of worsening CKD in patients with diabetes and the types of interventions proven to blunt this.

Much of the financial implication stems from the price of agents from the new drug classes now emphasized in the consensus recommendations – SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists. All these drugs currently remain on-patent with relatively expensive retail prices in the range of about $600 to $1,000/month.

Commenting on the cost concerns, Dr. Mottl highlighted that she currently has several patients in her practice on agents from two or more of these newer classes, and she has generally found it possible for patients to get much of their expenses covered by insurers and through drug-company assistance programs.

“The major gap is patients on Medicare,” she noted in an interview, because the Federal health insurance program does not allow beneficiaries to receive rebates for their drug costs. “The Diabetic Kidney Disease Collaborative is currently lobbying members of Congress to lift that barrier,” she emphasized.
 

Improved alignment

Details of the KDIGO recommendations feature in a guideline from that organization that appeared as a draft document online in March 2022. The ADA’s version recently appeared as an update to its Standards of Medical Care in Diabetes – 2022, as reported by this news organization. A panel of five KDIGO representatives and four members appointed by the ADA produced the harmonization statement.

Recommendations from both organizations were largely in agreement at the outset, but following the panel’s review, the two groups are now “very well-aligned,” said Peter Rossing, MD, DMSc, a diabetologist and professor at the Steno Diabetes Center, Copenhagen, and a KDIGO representative to the writing committee, who presented the joint statement at the ADA meeting.

“These are very important drugs that are vastly underused,” commented Josef Coresh, MD, PhD, an epidemiologist and professor at Johns Hopkins Bloomberg School of Public Health, Baltimore, who specializes in CKD and was not involved with the new statement.

“Coherence and simplicity are what we need so that there are no excuses about moving forward” with the recommended combination treatment, he stressed.

Moving too slow

“No one is resisting using these new medications, but they are just moving too slowly, and data now show that it’s moving more slowly in the United States than elsewhere. That may be partly because U.S. patients are charged much more for these drugs, and partly because U.S. health care is so much more fragmented,” Dr. Coresh said in an interview.

The new joint consensus statement may help, “but the fragmentation of the United States system and COVID-19 are big enemies” for any short-term increased use of the highlighted agents, he added.

Evidence for low U.S. use of SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists is becoming well known.

Dr. Rossing cited a 2019 report from the CURE-CKD registry of more than 600,000 U.S. patients with CKD showing that less than 1% received an SGLT2 inhibitor and less than 1% a GLP-1 receptor agonist. Not all these patients had diabetes, but a subgroup analysis of those with diabetes, prediabetes, or hypertension showed that usage of each of these two classes remained at less than 1% even in this group.

A separate report at the ADA meeting documented that of more than 1.3 million people with type 2 diabetes in the U.S. Veterans Affairs Healthcare System during 2019 and 2020, just 10% received an SGLT2 inhibitor and 7% a GLP-1 receptor agonist. And this is in a setting where drug cost is not a limiting factor.

In addition to focusing on the updated scheme for drug intervention in the consensus statement, Dr. Rossing highlighted several other important points that the writing committee emphasized.

Lifestyle optimization is a core first-line element of managing patients with diabetes and CKD, including a healthy diet, exercise, smoking cessation, and weight control. Other key steps for management include optimization of blood pressure, glucose, and lipids. The statement also calls out a potentially helpful role for continuous glucose monitoring in patients with type 1 or type 2 diabetes and CKD.

The statement notes that patients who also have atherosclerotic cardiovascular disease usually qualify for and could potentially benefit from more intensified lipid management with ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, as well as a potential role for treatment with antiplatelet agents.
 

‘If you don’t screen, you won’t find it’

Dr. Rossing also stressed the importance of regular screening for the onset of advanced CKD in patients. Patients whose estimated glomerular filtration rate (eGFR) drops below 60 mL/min/1.73m2, as well as those who develop microalbuminuria with a urinary albumin-to-creatinine ratio of at least 30 mg/g (30 mg/mmol), have a stage of CKD that warrants the drug interventions he outlined.

Guidelines from both the ADA and KDIGO were already in place, recommending annual screening of patients with diabetes for both these parameters starting at diagnosis of type 2 diabetes or 5 years following initial diagnosis of type 1 diabetes.

“If you don’t screen, you won’t find it, and you won’t be able to treat,” Dr. Rossing warned. He also highlighted the panel’s recommendation to treat these patients with an SGLT2 inhibitor as long as their eGFR is at least 20 mL/min/1.73m2. Treatment can then continue even when their eGFR drops lower.

Starting treatment with finerenone requires that patients have a normal level of serum potassium, he emphasized.

One reason for developing the new ADA and KDIGO statement is that “discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices,” write Katherine R. Tuttle, MD, and associates in a recent commentary.

The goal of the new statement is to harmonize and promote the shared recommendations of the two organizations, added Dr. Tuttle, who is executive director for research at Providence Healthcare, Spokane, Washington, and a KDIGO representative on the statement writing panel.

Dr. Mottl has reported being a consultant to Bayer. Dr. Rossing has reported being a consultant to or speaker on behalf of Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, MSD, Mundipharma, Novo Nordisk, Sanofi Aventis, and Vifor, as well as receiving research grants from AstraZeneca and Novo Nordisk. Dr. Coresh has reported no relevant financial relationships. Dr. Tuttle has reported being a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; receiving honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, Goldfinch Bio, Novo Nordisk, and Travere; and receiving research funding from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere.

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

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Individuals with diabetes who experience COVID-19 are at increased risk for long COVID compared to individuals without diabetes, according to data from a literature review of seven studies.

Diabetes remains a risk factor for severe COVID-19, but whether it is a risk factor for postacute sequelae of COVID-19 (PASC), also known as long COVID, remains unclear, Jessica L. Harding, PhD, of Emory University, said in a late-breaking poster session at the annual scientific sessions of the American Diabetes Association.

Long COVID is generally defined as “sequelae that extend beyond the 4 weeks after initial infection” and may include a range of symptoms that affect multiple organs, Dr. Harding said. A study conducted in January of 2022 suggested that type 2 diabetes was one of several strong risk factors for long COVID, she noted.

Dr. Harding and colleagues reviewed data from seven studies published from Jan. 1, 2020, to Jan. 27, 2022, on the risk of PASC in people with and without diabetes. The studies included patients with a minimum of 4 weeks’ follow-up after COVID-19 diagnosis. All seven studies had a longitudinal cohort design, and included adults from high-income countries, with study populations ranging from 104 to 4,182.

Across the studies, long COVID definitions varied, but included ongoing symptoms of fatigue, cough, and dyspnea, with follow-up periods of 4 weeks to 7 months.

Overall, three of the seven studies indicated that diabetes was a risk factor for long COVID (odds ratio [OR] greater than 4 for all) and four studies indicated that diabetes was not a risk factor for long COVID (OR, 0.5-2.2).

One of the three studies showing increased risk included 2,334 individuals hospitalized with COVID-19; of these about 5% had diabetes. The odds ratio for PASC for individuals with diabetes was 4.18. In another study of 209 persons with COVID-19, of whom 22% had diabetes, diabetes was significantly correlated with respiratory viral disease (meaning at least two respiratory symptoms). The third study showing an increased risk of long COVID in diabetes patients included 104 kidney transplant patients, of whom 20% had diabetes; the odds ratio for PASC was 4.42.

The findings were limited by several factors, including the relatively small number of studies and the heterogeneity of studies regarding definitions of long COVID, specific populations at risk, follow-up times, and risk adjustment, Dr. Harding noted.

More high-quality studies across multiple populations and settings are needed to determine if diabetes is indeed a risk factor for long COVID, she said.

In the meantime, “careful monitoring of people with diabetes for development of PASC may be advised,” Dr. Harding concluded.
 

Findings support need for screening

“Given the devastating impact of COVID on people with diabetes, it’s important to know what data has been accumulated on long COVID for future research and discoveries in this area,” Robert A. Gabbay, MD, chief science and medical officer for the American Diabetes Association, said in an interview. “The more information we have, the better we can understand the implications.”

Courtesy Joslin Diabetes Center

Dr. Gabbay said he was surprised by the current study findings. “We know very little on this subject, so yes, I am surprised to see just how significant the risk of long COVID for people with diabetes seems to be, but clearly, more research needs to be done to understand long COVID,” he emphasized.

The take-home message for clinicians is the importance of screening patients for PASC; also “ask your patients if they had COVID, to better understand any symptoms they might have that could be related to PACS,” he noted. 

“It is crucial that we confirm these results and then look at risk factors in people with diabetes that might explain who is at highest risk and ultimately understand the causes and potential cure,” Dr. Gabbay added.

The study was supported by the National Heart, Lung, and Blood Institute. Dr. Harding and Dr. Gabbay had no financial conflicts to disclose.

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

Ventricular arrhythmias more commonly occur on days when there are higher levels of air pollution, especially with fine particulate matter (PM), a new study suggests.

The investigators studied the relationship between air pollution and ventricular arrhythmias in Piacenza, Italy by examining 5-year data on patients who received an implantable cardioverter defibrillator (ICD).

Thomas321/iStock/Getty Images Plus

They found a significant association between PM2.5 levels and ventricular arrhythmias, especially those treated with direct current shock. Moreover, higher levels of PM2.5 and PM10 were associated with increased risk of all ventricular arrhythmias.

“These data confirm that environmental pollution is not only a climate emergency but also a public health problem,” lead author Alessia Zanni, currently at Maggiore Hospital, Bologna, Italy, and previously at Piacenza Hospital, said in an interview.

“The study suggests that the survival of patients with heart disease is affected not only by pharmacological therapies and advances in cardiology, but also by the air that they breathe,” she said.

The results were presented at European Society of Cardiology Heart Failure 2022.
 

More ED visits

The World Health Organization estimates around 7 million people die every year from exposure to polluted air, “as 91% of the world’s population lives in areas where air contaminants exceed safety levels,” Dr. Zanni said. Furthermore, “air pollution has been defined as the fourth-highest ranking risk factor for mortality – more important than LDL cholesterol, obesity, physical activity, or alcohol use.”

She noted that Piacenza has “historically been very attentive to the issues of early defibrillation and cardiac arrest.” Her group had previously found a correlation between out-of-hospital cardiac arrests and air pollution in the general population.

Moreover, her group recently observed that ED visits for patients with ICDs “tended to cluster; on some special days, many patients with ICDs had cardiac arrhythmias, and during those days, air pollution levels were particularly high.”

Her group therefore decided to compare the concentration of air pollutants on days when patients suffered from an arrhythmia event versus pollution levels on days without an arrhythmia, she said.
 

Further piece in a complex puzzle

The researchers studied 146 patients with ICDs between January 2013 and December 2017, assigning exposures (short, mid, and long term) to these patients based on their residential addresses.

They extracted day-by-day urban PM10, PM2.5, CO, NO₂, and O₃ levels from the Environmental Protection Agency monitoring stations and then, using time-stratified case-crossover analysis methodology, they calculated the association of ventricular arrhythmia onset with 0- to 7-day moving averages of the various air pollutants prior to the event.

Patients had received their ICD to control cardiac dysfunction brought on by previous myocardial infarction (n = 93), genetic or inflammatory conditions (n = 53), secondary prevention after a lethal arrhythmia (n = 67), and primary prevention (n = 79).

Of the 440 ventricular arrhythmias recorded, 322 were treated with antitachycardia pacing, while the remaining 118 were treated with direct current shock.

The researchers found a significant association between PM2.5 levels and ventricular arrhythmia treated with shock, corresponding to a 15% increased risk or every additional 10mg/m³ (P < .019).

They also found that, when PM2.5 concentrations were elevated by 1 mg/m³ for an entire week, compared with average levels, there was a 2.4% higher likelihood of ventricular arrhythmias, regardless of the temperature, and when PM10 was 1 mg/m³ above average for a week, there was a 2.1% increased risk for arrhythmias (odds ratio, 1,024; 95% confidence interval, 1,009-1,040] and OR, 1,021; 95% CI, 1,009-1,033, respectively), Dr. Zanni reported.

“Since the majority of out-of-hospital cardiac arrest causes still remain unclear, our data add a further piece to the complex puzzle of cardiac arrest triggers,” Dr. Zanni commented. “We think that particulate matter can cause acute inflammation of the heart muscle and potentially act as a trigger for lethal cardiac arrhythmias.

“As these toxic particles are emitted from power plants, industries, and cars, we think that cardiovascular research should highlight these new findings to promote green projects among the general population, clarifying the risks to the health of the human being, and we think strategies to prevent air pollutant exposure in high-risk patients [with previous cardiac disease] should be developed,” she added.

Further, “we advise patients at risk, during days with high PM2.5 (> 35 mg/m³) and PM10 (> 50 mg/m³) to use a mask of the N95 type outdoors, to reduce time spent outdoors – particularly in traffic – and to improve home air filtration,” Dr. Zanni said.
 

Entering the mainstream

In a comment, Joel Kaufman, MD, MPH, professor of internal medicine and environmental health, University of Washington, Seattle, said the study “adds to a fairly substantial literature already on this topic of short-term exposure to air pollution.”

The evidence that air pollutants “can be a trigger of worsening of cardiovascular disease is fairly consistent at this time, and although the effect sizes are small, they are consistent,” said Dr. Kaufman, who was the chair of the writing group for the American Heart Association’s 2020 policy statement, “Guidance to Reduce Cardiovascular Burden of Ambient Air Pollutants.”

“The research into this issue has become clearer during the past 10 years but still is not in the mainstream of most cardiologists’ awareness. They tend to focus more on controlling cholesterol and performing procedures, etc., but there are modifiable risk factors like air pollution that are increasingly recognized as being part of the picture,” said Dr. Kaufman, who was not involved with the current study.

Dr. Zanni added: “It is important that politics work hand in hand with the scientific community in order to win the battle against global warming, which will reduce the number of cardiovascular deaths – the leading cause of death worldwide – as well as environmental integrity.”

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Dr. Zanni and coauthors and Dr. Kaufman reported no relevant financial relationships.

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

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

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

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

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

The U.S. National Lipid Association has issued a new scientific statement on the management of patients with statin intolerance, which recommends different strategies to help patients stay on statin medications, and also suggests alternatives that can be used in patients who really cannot tolerate statin drugs.

The statement was published online in the Journal of Clinical Lipidology.  

It notes that, although statins are generally well tolerated, statin intolerance is reported in 5%-30% of patients and contributes to reduced statin adherence and persistence, as well as higher risk for adverse cardiovascular outcomes.

RogerAshford/Thinkstock

The statement acknowledges the importance of identifying modifiable risk factors for statin intolerance and recognizes the possibility of a “nocebo” effect, basically the patient expectation of harm resulting in perceived side effects.

To identify a tolerable statin regimen, it recommends that clinicians consider using several different strategies (different statin, dose, and/or dosing frequency), and to classify a patient as having statin intolerance, a minimum of two statins should have been attempted, including at least one at the lowest-approved daily dosage.

The statement says that nonstatin therapy may be required for patients who cannot reach therapeutic objectives with lifestyle and maximal tolerated statin therapy, and in these cases, therapies with outcomes data from randomized trials showing reduced cardiovascular events are favored.

In high and very high-risk patients who are statin intolerant, clinicians should consider initiating nonstatin therapy while additional attempts are made to identify a tolerable statin in order to limit the time of exposure to elevated levels of atherogenic lipoproteins, it suggests.

“There is strong evidence that statins reduce risk of cardiovascular events particularly in patients with atherosclerotic cardiovascular disease, but recent research shows that only about half of patients with ASCVD are on a statin,” Kevin C. Maki, PhD, coauthor of the statement and current president of the National Lipid Association, said in an interview.

“There is an urgent problem with underutilization of statins and undertreatment of ASCVD. And we know that perceived side effects associated with statins are a common reason for discontinuation of these drugs and the consequent failure to manage ASCVD adequately,” he said.  

Dr. Maki noted that the NLA’s first message is that, when experiencing symptoms taking statins, a large majority of patients can still tolerate a statin. “They can try a different agent or a different dose. But for those who still can’t tolerate a statin, we then recommend nonstatin therapies and we favor those therapies with evidence from randomized trials.”

He pointed out that many patients who believe they are experiencing side effects from taking statins still experience the same effects on a placebo, a condition known as the nocebo effect.

“Several studies have shown that the nocebo effect is very common and accounts for more than half of perceived statin side effects. It is therefore estimated that many of the complaints of statin intolerance are probably not directly related to the pharmacodynamic actions of the drugs,” Dr. Maki said.

One recent study on the nocebo effect, the SAMSON study, suggested that 90% of symptoms attributed to statins were elicited by placebo tablets too.

But Dr. Maki added that it can be a losing battle for the clinician if patients think their symptoms are related to taking a statin.

“We suggest that clinicians inform patients that most people can tolerate a statin – maybe with a different agent or an alternative dose – and it is really important to lower LDL cholesterol as that will lower the risk of MI and stroke, so we need to find a regimen that works for each individual,” he said. “Most people can find a regimen that works. If this means taking a lower dose of a statin, they can take some additional therapy as well. This is a better situation than stopping taking statins altogether and allowing ASCVD to progress.”

Dr. Maki stressed that statins should still be the first choice as they are effective, taken orally, and inexpensive.

“Other medications do not have all these advantages. For example, PCSK9 inhibitors are very effective but they are expensive and injectable,” he noted. “And while ezetimibe [Zetia] is now generic so inexpensive, it has a more modest effect on LDL-lowering compared to statins, so by itself it is not normally enough for most patients to get to their target LDL, but it is an option for use in combination with a statin.”

He added that the NLA message is to do everything possible to keep patients on a statin, especially patients with preexisting ASCVD.

“We would like these patients to be on high-intensity statins. If they really can’t tolerate this, then they could be on a low-intensity statin plus an additional agent.”

Commenting on the NLA statement, SAMSON study coauthor James Howard, MB BChir, PhD, Imperial College London, said he had reservations about some of the recommendations.

“Whilst I think it is great news that the existence and importance of the nocebo effect is increasingly recognized in international guidelines and statements, I think we need to be very careful about recommending reduced doses and frequencies of statins,” Dr. Howard said.

“Studies such as SAMSON and StatinWISE indicate the vast majority of side effects reported by patients taking statins are not caused by the statin molecule, but instead are caused by either the nocebo effect, or ever-present background symptoms that are wrongly attributed to the statins,” he commented. “Therefore, to recommend that the correct approach in a patient with a history of MI suffering symptoms on 80 mg of atorvastatin is to reduce the dose or try alternate daily dosing. This reinforces the view that these drugs are side-effect prone and need to be carefully titrated.”

Dr. Howard suggested that patients should be educated on the possibility of the nocebo effect or background symptoms and encouraged to retrial statins at the same dose. “If that doesn’t work, then formal recording with a symptom diary might help patients recognize background symptoms,” he added.

Dr. Howard noted that, if symptoms still persist, an “n-of-1” trial could be conducted, in which the patient rotates between multiple periods of taking a statin and a placebo, but he acknowledged that this is expensive and time consuming. 

Also commenting, Steve Nissen, MD, Cleveland Clinic, said he thought the NLA statement was “reasonable and thoughtful.”

“Regardless of whether the symptoms are due to the nocebo effect or not, some patients will just not take a statin no matter how hard you try to convince them to persevere, so we do need alternatives,” Dr. Nissen said.

He noted that current alternatives would include the PCSK9 inhibitors and ezetimibe, but a future candidate could be the oral bempedoic acid (Nexletol), which is currently being evaluated in a large outcomes trial (CLEAR Outcomes).

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

Your gut microbiome will thank you later

A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?

In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.

Beer? Yes. Beer.

Engin Akyurt/Pixabay

We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?

In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.

So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
 

We’ve lost our minds, but at least we know how fast they’re going

The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”

Massimiliano De Deo, LNGS-INFN

When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.

To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.

That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.

The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
 

Missing links: A real fish story

Dear LOTME:

Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?

Restless in Roswell

Dear Restless:

The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.

IVPP

For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?

The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.

“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.

In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.

So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
 

Can you lend me an ear?

If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?

850977/Pixabay

Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?

“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.

And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”

The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!

Your gut microbiome will thank you later

A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?

In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.

Beer? Yes. Beer.

Engin Akyurt/Pixabay

We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?

In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.

So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
 

We’ve lost our minds, but at least we know how fast they’re going

The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”

Massimiliano De Deo, LNGS-INFN

When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.

To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.

That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.

The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
 

Missing links: A real fish story

Dear LOTME:

Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?

Restless in Roswell

Dear Restless:

The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.

IVPP

For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?

The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.

“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.

In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.

So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
 

Can you lend me an ear?

If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?

850977/Pixabay

Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?

“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.

And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”

The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!

Your gut microbiome will thank you later

A healthy gut seems like the new catch-all to better overall health these days. Nutrition and diet culture has us drinking kombucha and ginger tea and coffee, but what if we told you that going to happy hour might also help?

In a recent double-blind study published in the Journal of Agricultural and Food Chemistry, 19 men were divided into two groups and asked to drink 11 ounces of alcoholic lager (5.2% by volume) or nonalcoholic lager with dinner for 4 weeks.

Beer? Yes. Beer.

Engin Akyurt/Pixabay

We humans have trillions of microorganisms running rampant through our digestive tracts. When they’re happy, we have a lower chance of developing heart disease and diabetes. You know what else has millions of happy microorganisms from fermentation? Beer. It also has polyphenols that can help the body’s tissues fight cancers, as well as heart disease and inflammation. So beer is looking a little more healthy now, isn’t it?

In the study, the researchers found that both the alcoholic- and nonalcoholic-lager groups had a boost in bacterial diversity in the gut and higher fecal alkaline phosphatase levels, which showed improved intestinal health. They acknowledged, however, that the nonalcoholic route would be safer and healthier for overall health.

So add a lager to the list of gut-healthy foods that you should be consuming. It may give the phrase “beer gut” a whole new meaning.
 

We’ve lost our minds, but at least we know how fast they’re going

The phrase “quantum consciousness” sounds like something out of a particularly cheesy episode of Star Trek: “Oh no, Captain, the quantum consciousness has invaded our computer, and the only way to drive it out is to reverse the polarity of a focused tachyon beam.”

Massimiliano De Deo, LNGS-INFN

When it comes to understanding such basic existential issues as the origin of consciousness, however, quantum mechanics wasn’t off the table. The theory of the quantum origin of consciousness dates back to the 1990s (thanks in part to noted physician Roger Penrose), and goes something like this: There are microtubules within neurons in the brain that are small enough and isolated enough from the warm, wet, and chaotic brain environment where quantum effects can briefly come into play. We’re talking miniscule fractions of a second here, but still, long enough for quantum calculations to take place in the form of system wavefunction collapse, courtesy of gravity.

To plunge even deeper into the rabbit hole of quantum mechanics, the reason Schrödinger’s cat doesn’t occur in real life is wavefunction collapse; the more massive a quantum system is, the more likely it is to collapse into one state or another (alive or dead, in the cat’s case). The quantum origin of consciousness, or Orch OR theory, holds that human consciousness arises from electrical oscillations within the neuronal microtubules caused by the computations stemming from the collapse of small quantum systems.

That is an awful lot of overly simplified explanation, especially considering the study that just came out essentially disproved it. Oops. The research, published in Physics of Life Reviews, is pretty simple. The researchers went to a lab deep underground to avoid interference from cosmic rays, and sat around for months, observing a chunk of germanium for signs of spontaneous radiation, attributable to the same sort of wavefunction collapse that is supposedly occurring in our brains. They found nothing out of the ordinary, pretty definitively disproving most of Orch OR theory.

The researchers were unwilling to completely dismiss the idea (this is quantum mechanics, after all, uncertainty kind of goes with the territory), but it does seem like we’ll have to search elsewhere for sources of human consciousness. Personally, we’re big fans of the cymbal-playing monkey.
 

Missing links: A real fish story

Dear LOTME:

Ear’s a question that’s been keeping me up at night. Is the human middle ear the result of top-secret government experiments involving alien technology, Abraham Lincoln, and the Illuminati?

Restless in Roswell

Dear Restless:

The paleoanthropologic community has been sorting through this mystery for decades, and fossils discovered in China over the past 20 years finally provide a much less conspiratorially satisfying answer.

IVPP

For some time now, experts in the field have believed that the bones of the human middle ear evolved from the spiracular gill of a fish. The spiracle is a small hole behind each eye that opens to the mouth in some fishes and was used to breathe air in the earliest, most primitive species. But how did we get from spiracle to ear?

The missing links come in the form of the cranial anatomy of Shuyu, a 438-million-year-old, fingernail-sized skull of a jawless fish, and the 419-million-year-old fossil of a completely preserved fish with gill filaments in the first branchial chamber.

“These fossils provided the first anatomical and fossil evidence for a vertebrate spiracle originating from fish gills,” senior author Gai Zhikun, PhD, of the Institute of Vertebrate Paleontology and Paleoanthropology, Beijing, said in a written statement.

In many ways, it seems, we are fish: “Many important structures of human beings can be traced back to our fish ancestors, such as our teeth, jaws, middle ears, etc,” added Zhu Min, PhD, also of the institute.

So, Restless, the next time you hear the soothing sounds of an angry mob storming the Capitol or you chew on a slab, slice, or chunk of mutant, laboratory-produced chicken in your favorite fast-food restaurant, be sure to thank Shuyu.
 

Can you lend me an ear?

If you thought locusts were only a nuisance, think again. They have their uses. If you take a locust’s ear and put it inside a robot, the robot will be able to hear and receive signals. Who knew?

850977/Pixabay

Researchers from Tel Aviv University in Israel showed the robot’s hearing abilities by giving clap signals that told the robot what to do: One clap means go forward, two claps mean move back. What do you think the robot would do if it heard the clap break from Cha Cha Slide?

“Our task was to replace the robot’s electronic microphone with a dead insect’s ear, use the ear’s ability to detect the electrical signals from the environment, in this case vibrations in the air, and, using a special chip, convert the insect input to that of the robot,” Ben M. Maoz, PhD, said in a statement from the university.

And how does a dead locust ear work in a robot? Well, Dr. Maoz explained: “My laboratory has developed a special device – Ear-on-a-Chip – that allows the ear to be kept alive throughout the experiment by supplying oxygen and food to the organ while allowing the electrical signals to be taken out of the locust’s ear and amplified and transmitted to the robot.”

The research won’t stop at hearing, he said, as the other four senses also will be taken into consideration. This could help us sense dangers in the future, such as earthquakes or diseases. We said it before and we’ll say it again: We’re rooting for you, science!

A phase 3 trial has associated the neurokinin-3 (NK3)–receptor inhibitor fezolinetant, an oral therapy taken once daily, with substantial control over the symptoms of menopause, according to results of the randomized SKYLIGHT 2 trial.

The nonhormonal therapy has the potential to address an important unmet need, Genevieve Neal-Perry, MD, PhD, said at the annual meeting of the Endocrine Society.

The health risks of hormone therapy (HT) have “caused quite a few women to consider whether hormone replacement is right for them, and, in addition, there are other individuals who have hormone-responsive cancers or other disorders that might prohibit them [from using HT],” Dr. Neal-Perry said.

The NK3 receptor stimulates the thermoregulatory center in the hypothalamus. By blocking the NK3 receptor, vasodilation and other downstream effects are inhibited, explained Dr. Neal-Perry. She credited relatively recent advances in understanding the mechanisms of menopausal symptoms for identifying this and other potentially targetable mediators.

SKYLIGHT 2 trial: Two phases

In the double-blind multinational phase 3 SKYLIGHT 2 trial, 484 otherwise healthy symptomatic menopausal women were randomized to 30 mg of fezolinetant, 45 mg of fezolinetant, or placebo. The 120 participating centers were in North American and Europe.

In the first phase, safety and efficacy were evaluated over 12 weeks. In a second extension phase, placebo patients were rerandomized to one of the fezolinetant study doses. Those on active therapy remained in their assigned groups. All patients were then followed for an additional 40 weeks.

The coprimary endpoints were frequency and severity of moderate to severe vasomotor symptoms as reported by patients using an electronic diary. There were several secondary endpoints, including patient-reported outcomes regarding sleep quality.

As expected from other controlled trials, placebo patients achieved about a 40% reduction in moderate to severe vasomotor symptom frequency over the first 12 weeks. Relative to placebo, symptom frequency declined more quickly and steeply on fezolinetant. By week 12, both achieved reductions of about 60%. Statistical P values for the differences in the three arms were not provided, but Dr. Neal-Perry reported they were significant.

Vasomotor severity, like frequency, is reduced

The change in vasomotor severity, which subjects in the trial rated as better or worse, was also significant. The differences in the severity curves were less, but they separated in favor of the two active treatment arms by about 2 weeks, and the curves continued to show an advantage for fezolinetant over both the first 12 weeks and then the remaining 40 weeks.

Overall, the decline in vasomotor symptom frequency remained on a persistent downward slope on both doses of fezolinetant for the full 52 weeks of the study, so that the reduction at 52 weeks was on the order of 25% greater than that seen at 12 weeks.

At 52 weeks, “you can see that individuals on placebo who were crossed over to an active treatment had a significant reduction in their hot flashes and look very much like those who were randomized to fezolinetant at the beginning of the study,” said Dr. Neal-Perry, who is chair of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Other outcomes also favored fezolinetant over placebo. For example, a reduction in sleep disturbance observed at 12 weeks was sustained over the full 52 weeks of the study. The reduction in sleep symptoms appeared to be slightly greater on the higher dose, but the benefit at 52 weeks among patients after the crossover was similar on either active arm.

No serious side effects identified

There were no serious drug-related treatment-emergent adverse events in any treatment group. One patient in the placebo arm (< 1%), two patients in the 30-mg fezolinetant arm (1.2%), and five patients in the 45-mg arm (3%) discontinued therapy for an adverse event considered to be treatment related.

“The most common side effect associated with fezolinetant was headache. There were no other side effects that led patients to pull out of the study,” Dr. Neal-Perry reported at the meeting, which was held in Atlanta and virtually.

According to Dr. Neal-Perry the vasomotor symptoms relative to menopause, which occur in almost all women, are moderate to severe in an estimated 35%-45%. Some groups, such as those with an elevated body mass index and African Americans, appear to be at even greater risk. Study enrollment was specifically designed to include these high-risk groups, but the subgroup efficacy data have not yet been analyzed.

Other drugs with a similar mechanism of action have not been brought forward because of concern about elevated liver enzymes, but Dr. Neal-Perry said that this does not appear to be an issue for fezolinetant, which was designed with greater specificity for the NK3 target than previous treatments.

If fezolinetant is approved, Dr. Neal-Perry expects this agent to fulfill an important unmet need because of the limitations of other nonhormonal solutions for control of menopause symptoms.

HT alternatives limited

For control of many menopause symptoms, particularly hot flashes, hormone therapy (HT) is the most efficacious, but Richard J. Santen, MD, emeritus professor and an endocrinologist at the University of Virginia, Charlottesville, agreed there is a need for alternatives.

In addition to those who have contraindications for HT, Dr. Santen said in an interview that this option is not acceptable to others “for a variety of reasons.” The problem is that the alternatives are limited.

“The SSRI agents and gabapentin are alternative nonhormonal agents, but they have side effects and are not as effective,” he said. Hot flashes “can be a major disruptor of quality of life,” so he is intrigued with the positive results achieved with fezolinetant.

“A new drug such as reported at the Endocrine Society meeting would be an important new addition to the armamentarium,” he said.

Dr. Neal-Perry reports no conflicts of interest.

A phase 3 trial has associated the neurokinin-3 (NK3)–receptor inhibitor fezolinetant, an oral therapy taken once daily, with substantial control over the symptoms of menopause, according to results of the randomized SKYLIGHT 2 trial.

The nonhormonal therapy has the potential to address an important unmet need, Genevieve Neal-Perry, MD, PhD, said at the annual meeting of the Endocrine Society.

The health risks of hormone therapy (HT) have “caused quite a few women to consider whether hormone replacement is right for them, and, in addition, there are other individuals who have hormone-responsive cancers or other disorders that might prohibit them [from using HT],” Dr. Neal-Perry said.

The NK3 receptor stimulates the thermoregulatory center in the hypothalamus. By blocking the NK3 receptor, vasodilation and other downstream effects are inhibited, explained Dr. Neal-Perry. She credited relatively recent advances in understanding the mechanisms of menopausal symptoms for identifying this and other potentially targetable mediators.

SKYLIGHT 2 trial: Two phases

In the double-blind multinational phase 3 SKYLIGHT 2 trial, 484 otherwise healthy symptomatic menopausal women were randomized to 30 mg of fezolinetant, 45 mg of fezolinetant, or placebo. The 120 participating centers were in North American and Europe.

In the first phase, safety and efficacy were evaluated over 12 weeks. In a second extension phase, placebo patients were rerandomized to one of the fezolinetant study doses. Those on active therapy remained in their assigned groups. All patients were then followed for an additional 40 weeks.

The coprimary endpoints were frequency and severity of moderate to severe vasomotor symptoms as reported by patients using an electronic diary. There were several secondary endpoints, including patient-reported outcomes regarding sleep quality.

As expected from other controlled trials, placebo patients achieved about a 40% reduction in moderate to severe vasomotor symptom frequency over the first 12 weeks. Relative to placebo, symptom frequency declined more quickly and steeply on fezolinetant. By week 12, both achieved reductions of about 60%. Statistical P values for the differences in the three arms were not provided, but Dr. Neal-Perry reported they were significant.

Vasomotor severity, like frequency, is reduced

The change in vasomotor severity, which subjects in the trial rated as better or worse, was also significant. The differences in the severity curves were less, but they separated in favor of the two active treatment arms by about 2 weeks, and the curves continued to show an advantage for fezolinetant over both the first 12 weeks and then the remaining 40 weeks.

Overall, the decline in vasomotor symptom frequency remained on a persistent downward slope on both doses of fezolinetant for the full 52 weeks of the study, so that the reduction at 52 weeks was on the order of 25% greater than that seen at 12 weeks.

At 52 weeks, “you can see that individuals on placebo who were crossed over to an active treatment had a significant reduction in their hot flashes and look very much like those who were randomized to fezolinetant at the beginning of the study,” said Dr. Neal-Perry, who is chair of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Other outcomes also favored fezolinetant over placebo. For example, a reduction in sleep disturbance observed at 12 weeks was sustained over the full 52 weeks of the study. The reduction in sleep symptoms appeared to be slightly greater on the higher dose, but the benefit at 52 weeks among patients after the crossover was similar on either active arm.

No serious side effects identified

There were no serious drug-related treatment-emergent adverse events in any treatment group. One patient in the placebo arm (< 1%), two patients in the 30-mg fezolinetant arm (1.2%), and five patients in the 45-mg arm (3%) discontinued therapy for an adverse event considered to be treatment related.

“The most common side effect associated with fezolinetant was headache. There were no other side effects that led patients to pull out of the study,” Dr. Neal-Perry reported at the meeting, which was held in Atlanta and virtually.

According to Dr. Neal-Perry the vasomotor symptoms relative to menopause, which occur in almost all women, are moderate to severe in an estimated 35%-45%. Some groups, such as those with an elevated body mass index and African Americans, appear to be at even greater risk. Study enrollment was specifically designed to include these high-risk groups, but the subgroup efficacy data have not yet been analyzed.

Other drugs with a similar mechanism of action have not been brought forward because of concern about elevated liver enzymes, but Dr. Neal-Perry said that this does not appear to be an issue for fezolinetant, which was designed with greater specificity for the NK3 target than previous treatments.

If fezolinetant is approved, Dr. Neal-Perry expects this agent to fulfill an important unmet need because of the limitations of other nonhormonal solutions for control of menopause symptoms.

HT alternatives limited

For control of many menopause symptoms, particularly hot flashes, hormone therapy (HT) is the most efficacious, but Richard J. Santen, MD, emeritus professor and an endocrinologist at the University of Virginia, Charlottesville, agreed there is a need for alternatives.

In addition to those who have contraindications for HT, Dr. Santen said in an interview that this option is not acceptable to others “for a variety of reasons.” The problem is that the alternatives are limited.

“The SSRI agents and gabapentin are alternative nonhormonal agents, but they have side effects and are not as effective,” he said. Hot flashes “can be a major disruptor of quality of life,” so he is intrigued with the positive results achieved with fezolinetant.

“A new drug such as reported at the Endocrine Society meeting would be an important new addition to the armamentarium,” he said.

Dr. Neal-Perry reports no conflicts of interest.

A phase 3 trial has associated the neurokinin-3 (NK3)–receptor inhibitor fezolinetant, an oral therapy taken once daily, with substantial control over the symptoms of menopause, according to results of the randomized SKYLIGHT 2 trial.

The nonhormonal therapy has the potential to address an important unmet need, Genevieve Neal-Perry, MD, PhD, said at the annual meeting of the Endocrine Society.

The health risks of hormone therapy (HT) have “caused quite a few women to consider whether hormone replacement is right for them, and, in addition, there are other individuals who have hormone-responsive cancers or other disorders that might prohibit them [from using HT],” Dr. Neal-Perry said.

The NK3 receptor stimulates the thermoregulatory center in the hypothalamus. By blocking the NK3 receptor, vasodilation and other downstream effects are inhibited, explained Dr. Neal-Perry. She credited relatively recent advances in understanding the mechanisms of menopausal symptoms for identifying this and other potentially targetable mediators.

SKYLIGHT 2 trial: Two phases

In the double-blind multinational phase 3 SKYLIGHT 2 trial, 484 otherwise healthy symptomatic menopausal women were randomized to 30 mg of fezolinetant, 45 mg of fezolinetant, or placebo. The 120 participating centers were in North American and Europe.

In the first phase, safety and efficacy were evaluated over 12 weeks. In a second extension phase, placebo patients were rerandomized to one of the fezolinetant study doses. Those on active therapy remained in their assigned groups. All patients were then followed for an additional 40 weeks.

The coprimary endpoints were frequency and severity of moderate to severe vasomotor symptoms as reported by patients using an electronic diary. There were several secondary endpoints, including patient-reported outcomes regarding sleep quality.

As expected from other controlled trials, placebo patients achieved about a 40% reduction in moderate to severe vasomotor symptom frequency over the first 12 weeks. Relative to placebo, symptom frequency declined more quickly and steeply on fezolinetant. By week 12, both achieved reductions of about 60%. Statistical P values for the differences in the three arms were not provided, but Dr. Neal-Perry reported they were significant.

Vasomotor severity, like frequency, is reduced

The change in vasomotor severity, which subjects in the trial rated as better or worse, was also significant. The differences in the severity curves were less, but they separated in favor of the two active treatment arms by about 2 weeks, and the curves continued to show an advantage for fezolinetant over both the first 12 weeks and then the remaining 40 weeks.

Overall, the decline in vasomotor symptom frequency remained on a persistent downward slope on both doses of fezolinetant for the full 52 weeks of the study, so that the reduction at 52 weeks was on the order of 25% greater than that seen at 12 weeks.

At 52 weeks, “you can see that individuals on placebo who were crossed over to an active treatment had a significant reduction in their hot flashes and look very much like those who were randomized to fezolinetant at the beginning of the study,” said Dr. Neal-Perry, who is chair of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.

Other outcomes also favored fezolinetant over placebo. For example, a reduction in sleep disturbance observed at 12 weeks was sustained over the full 52 weeks of the study. The reduction in sleep symptoms appeared to be slightly greater on the higher dose, but the benefit at 52 weeks among patients after the crossover was similar on either active arm.

No serious side effects identified

There were no serious drug-related treatment-emergent adverse events in any treatment group. One patient in the placebo arm (< 1%), two patients in the 30-mg fezolinetant arm (1.2%), and five patients in the 45-mg arm (3%) discontinued therapy for an adverse event considered to be treatment related.

“The most common side effect associated with fezolinetant was headache. There were no other side effects that led patients to pull out of the study,” Dr. Neal-Perry reported at the meeting, which was held in Atlanta and virtually.

According to Dr. Neal-Perry the vasomotor symptoms relative to menopause, which occur in almost all women, are moderate to severe in an estimated 35%-45%. Some groups, such as those with an elevated body mass index and African Americans, appear to be at even greater risk. Study enrollment was specifically designed to include these high-risk groups, but the subgroup efficacy data have not yet been analyzed.

Other drugs with a similar mechanism of action have not been brought forward because of concern about elevated liver enzymes, but Dr. Neal-Perry said that this does not appear to be an issue for fezolinetant, which was designed with greater specificity for the NK3 target than previous treatments.

If fezolinetant is approved, Dr. Neal-Perry expects this agent to fulfill an important unmet need because of the limitations of other nonhormonal solutions for control of menopause symptoms.

HT alternatives limited

For control of many menopause symptoms, particularly hot flashes, hormone therapy (HT) is the most efficacious, but Richard J. Santen, MD, emeritus professor and an endocrinologist at the University of Virginia, Charlottesville, agreed there is a need for alternatives.

In addition to those who have contraindications for HT, Dr. Santen said in an interview that this option is not acceptable to others “for a variety of reasons.” The problem is that the alternatives are limited.

“The SSRI agents and gabapentin are alternative nonhormonal agents, but they have side effects and are not as effective,” he said. Hot flashes “can be a major disruptor of quality of life,” so he is intrigued with the positive results achieved with fezolinetant.

“A new drug such as reported at the Endocrine Society meeting would be an important new addition to the armamentarium,” he said.

Dr. Neal-Perry reports no conflicts of interest.

Adults with type 1 diabetes had significantly better glycemic control on days they exercised, regardless of exercise type, compared to days when they were inactive, according to a prospective study in nearly 500 individuals.

Different types of exercise, such as aerobic workouts, interval training, or resistance training, may have different immediate glycemic effects in adults with type 1 diabetes (T1D), but the impact of exercise type on the percentage of time diabetes patients maintain glucose in the 70-180 mg/dL range on days when they are active vs. inactive has not been well studied, Zoey Li said in a presentation at the annual scientific sessions of the American Diabetes Association.

Yuri Nunes / EyeEm / Getty Images

In the Type 1 Diabetes Exercise Initiative (T1DEXI) study, Ms. Li and colleagues examined continuous glucose monitoring (CGM) data from 497 adults with T1D. The observational study included self-referred adults aged 18 years and older who had been living with T1D for at least 2 years. Participants were assigned to programs of aerobic exercise (defined as a target heart rate of 70%-80% of age-predicted maximum), interval exercise (defined as an interval heart rate of 80%-90% of age-predicted maximum), or resistance exercise (defined as muscle group fatigue after three sets of eight repetitions).

Participants completed the workouts at home via 30-minute videos at least six times over the 4-week study period. The study design involved an activity goal of at least 150 minutes per week, including the videos and self-reported usual activity, such as walking. The data were collected through an app designed for the study, a heart rate monitor, and a CGM.

The researchers compared glucose levels on days when the participants reported being active compared to days when they were sedentary. The goal of the study was to assess the effect of exercise type on time spent with glucose in the range of 70-180 mg/dL, defined as time in range (TIR).

The mean age of the participants was 37 years; 89% were White. The mean duration of diabetes was 18 years, and the mean hemoglobin A1c was 6.6%. “An astounding 95% were current continuous glucose monitoring [CGM] users,” said Ms. Li, a statistician at the Jaeb Center for Health Research in Tampa, Fla.

A total of 398 participants reported at least one exercise day and one sedentary day, for a total of 1,302 exercise days and 2,470 sedentary days.

Overall, the mean TIR was significantly higher on exercise days compared to sedentary days (75% vs. 70%, P < .001). The median time above 180 mg/dL also was significantly lower on exercise days compared to sedentary days (17% vs. 23%, P < .001), and mean glucose levels were 10 mg/dL lower on exercise days (145 mg/dL vs. 155 mg/dL)

“This all came with a slight hit to their time below range,” Ms. Li noted. The median time below 70 mg/dL was 1.1% on exercise days compared to 0.4% on sedentary days (P < .001). The percentage of days with hypoglycemic events was higher on exercise days compared to sedentary days (47% vs. 40%, P < .001), as they are related to time below 70 mg/dL, she added.

The differences for mean glucose level and TIR between exercise days and sedentary days were significant for each of the three exercise types, Ms. Li said.

“After establishing these glycemic trends, we looked at whether there were any factors that influenced the glycemic differences on exercise vs. sedentary days,” Ms. Li said.

Regardless of exercise type, age, sex, baseline A1c, diabetes duration, body mass index, insulin modality, CGM use, and percentage of time below range in the past 24 hours, there was higher TIR and higher hypoglycemia on exercise days compared to sedentary days.

Although the study was limited in part by the observational design, “with these data, we can better understand the glycemic benefits and disadvantages of exercise in adults with type 1 diabetes,” Ms. Li said.
 

Don’t forget the negative effects of exercise

“It is well known that the three types of exercise can modulate glucose levels. This can be very useful when attempting to reduce excessively high glucose levels, and when encouraging people to engage in frequent, regular, and consistent physical activity and exercise for general cardiovascular pulmonary and musculoskeletal health,” Helena W. Rodbard, MD, an endocrinologist in private practice in Rockville, Md., said in an interview.

“However, it was not known what effects various types of exercise would have on time in range (70-180 mg/dL) and time below range (< 70 mg/dL) measured over a full 24-hour period in people with type 1 diabetes,” said Dr. Rodbard, who was not involved with the study.

“I was surprised to see that the effect of the three different types of exercise were so similar,” Dr. Rodbard noted. “There had been previous reports suggesting that the time course of glucose could be different for these three types of exercise.”

The current study confirms prior knowledge that exercise can help reduce blood glucose, and increase TIR, said Dr. Rodbard. The study shows that TIR increases by roughly 5-7 percentage points (about 1 hour per day) and reduces mean glucose by 9-13 mg/dL irrespective of the three types of exercise,” she said. “There was a suggestion that the risk of increasing hypoglycemia below 70 mg/dL was less likely for resistance exercise than for the interval or aerobic types of exercise,” she noted.

As for additional research, “This study did not address the various ways in which one can mitigate the potentially deleterious effects of exercise, specifically with reference to rates of hypoglycemia, even mild symptomatic biochemical hypoglycemia,” said Dr. Rodbard. “Since the actual amount of time below 70 mg/dL is usually so small (0.3%-0.7% of the 1,440 minutes in the day, or about 5-10 minutes per day on average), it is difficult to measure and there is considerable variability between different people,” she emphasized. “Finding optimal and robust ways to achieve consistency in the reduction of glucose, between days within subjects, and between subjects, will need further examination of various types of protocols for diet, exercise and insulin administration, and of various methods for education of the patient,” she said.

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust. Ms. Li and Dr. Rodbard had no financial conflicts to disclose. Dr. Rodbard serves on the editorial advisory board of Clinical Endocrinology News.

Adults with type 1 diabetes had significantly better glycemic control on days they exercised, regardless of exercise type, compared to days when they were inactive, according to a prospective study in nearly 500 individuals.

Different types of exercise, such as aerobic workouts, interval training, or resistance training, may have different immediate glycemic effects in adults with type 1 diabetes (T1D), but the impact of exercise type on the percentage of time diabetes patients maintain glucose in the 70-180 mg/dL range on days when they are active vs. inactive has not been well studied, Zoey Li said in a presentation at the annual scientific sessions of the American Diabetes Association.

Yuri Nunes / EyeEm / Getty Images

In the Type 1 Diabetes Exercise Initiative (T1DEXI) study, Ms. Li and colleagues examined continuous glucose monitoring (CGM) data from 497 adults with T1D. The observational study included self-referred adults aged 18 years and older who had been living with T1D for at least 2 years. Participants were assigned to programs of aerobic exercise (defined as a target heart rate of 70%-80% of age-predicted maximum), interval exercise (defined as an interval heart rate of 80%-90% of age-predicted maximum), or resistance exercise (defined as muscle group fatigue after three sets of eight repetitions).

Participants completed the workouts at home via 30-minute videos at least six times over the 4-week study period. The study design involved an activity goal of at least 150 minutes per week, including the videos and self-reported usual activity, such as walking. The data were collected through an app designed for the study, a heart rate monitor, and a CGM.

The researchers compared glucose levels on days when the participants reported being active compared to days when they were sedentary. The goal of the study was to assess the effect of exercise type on time spent with glucose in the range of 70-180 mg/dL, defined as time in range (TIR).

The mean age of the participants was 37 years; 89% were White. The mean duration of diabetes was 18 years, and the mean hemoglobin A1c was 6.6%. “An astounding 95% were current continuous glucose monitoring [CGM] users,” said Ms. Li, a statistician at the Jaeb Center for Health Research in Tampa, Fla.

A total of 398 participants reported at least one exercise day and one sedentary day, for a total of 1,302 exercise days and 2,470 sedentary days.

Overall, the mean TIR was significantly higher on exercise days compared to sedentary days (75% vs. 70%, P < .001). The median time above 180 mg/dL also was significantly lower on exercise days compared to sedentary days (17% vs. 23%, P < .001), and mean glucose levels were 10 mg/dL lower on exercise days (145 mg/dL vs. 155 mg/dL)

“This all came with a slight hit to their time below range,” Ms. Li noted. The median time below 70 mg/dL was 1.1% on exercise days compared to 0.4% on sedentary days (P < .001). The percentage of days with hypoglycemic events was higher on exercise days compared to sedentary days (47% vs. 40%, P < .001), as they are related to time below 70 mg/dL, she added.

The differences for mean glucose level and TIR between exercise days and sedentary days were significant for each of the three exercise types, Ms. Li said.

“After establishing these glycemic trends, we looked at whether there were any factors that influenced the glycemic differences on exercise vs. sedentary days,” Ms. Li said.

Regardless of exercise type, age, sex, baseline A1c, diabetes duration, body mass index, insulin modality, CGM use, and percentage of time below range in the past 24 hours, there was higher TIR and higher hypoglycemia on exercise days compared to sedentary days.

Although the study was limited in part by the observational design, “with these data, we can better understand the glycemic benefits and disadvantages of exercise in adults with type 1 diabetes,” Ms. Li said.
 

Don’t forget the negative effects of exercise

“It is well known that the three types of exercise can modulate glucose levels. This can be very useful when attempting to reduce excessively high glucose levels, and when encouraging people to engage in frequent, regular, and consistent physical activity and exercise for general cardiovascular pulmonary and musculoskeletal health,” Helena W. Rodbard, MD, an endocrinologist in private practice in Rockville, Md., said in an interview.

“However, it was not known what effects various types of exercise would have on time in range (70-180 mg/dL) and time below range (< 70 mg/dL) measured over a full 24-hour period in people with type 1 diabetes,” said Dr. Rodbard, who was not involved with the study.

“I was surprised to see that the effect of the three different types of exercise were so similar,” Dr. Rodbard noted. “There had been previous reports suggesting that the time course of glucose could be different for these three types of exercise.”

The current study confirms prior knowledge that exercise can help reduce blood glucose, and increase TIR, said Dr. Rodbard. The study shows that TIR increases by roughly 5-7 percentage points (about 1 hour per day) and reduces mean glucose by 9-13 mg/dL irrespective of the three types of exercise,” she said. “There was a suggestion that the risk of increasing hypoglycemia below 70 mg/dL was less likely for resistance exercise than for the interval or aerobic types of exercise,” she noted.

As for additional research, “This study did not address the various ways in which one can mitigate the potentially deleterious effects of exercise, specifically with reference to rates of hypoglycemia, even mild symptomatic biochemical hypoglycemia,” said Dr. Rodbard. “Since the actual amount of time below 70 mg/dL is usually so small (0.3%-0.7% of the 1,440 minutes in the day, or about 5-10 minutes per day on average), it is difficult to measure and there is considerable variability between different people,” she emphasized. “Finding optimal and robust ways to achieve consistency in the reduction of glucose, between days within subjects, and between subjects, will need further examination of various types of protocols for diet, exercise and insulin administration, and of various methods for education of the patient,” she said.

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust. Ms. Li and Dr. Rodbard had no financial conflicts to disclose. Dr. Rodbard serves on the editorial advisory board of Clinical Endocrinology News.

Adults with type 1 diabetes had significantly better glycemic control on days they exercised, regardless of exercise type, compared to days when they were inactive, according to a prospective study in nearly 500 individuals.

Different types of exercise, such as aerobic workouts, interval training, or resistance training, may have different immediate glycemic effects in adults with type 1 diabetes (T1D), but the impact of exercise type on the percentage of time diabetes patients maintain glucose in the 70-180 mg/dL range on days when they are active vs. inactive has not been well studied, Zoey Li said in a presentation at the annual scientific sessions of the American Diabetes Association.

Yuri Nunes / EyeEm / Getty Images

In the Type 1 Diabetes Exercise Initiative (T1DEXI) study, Ms. Li and colleagues examined continuous glucose monitoring (CGM) data from 497 adults with T1D. The observational study included self-referred adults aged 18 years and older who had been living with T1D for at least 2 years. Participants were assigned to programs of aerobic exercise (defined as a target heart rate of 70%-80% of age-predicted maximum), interval exercise (defined as an interval heart rate of 80%-90% of age-predicted maximum), or resistance exercise (defined as muscle group fatigue after three sets of eight repetitions).

Participants completed the workouts at home via 30-minute videos at least six times over the 4-week study period. The study design involved an activity goal of at least 150 minutes per week, including the videos and self-reported usual activity, such as walking. The data were collected through an app designed for the study, a heart rate monitor, and a CGM.

The researchers compared glucose levels on days when the participants reported being active compared to days when they were sedentary. The goal of the study was to assess the effect of exercise type on time spent with glucose in the range of 70-180 mg/dL, defined as time in range (TIR).

The mean age of the participants was 37 years; 89% were White. The mean duration of diabetes was 18 years, and the mean hemoglobin A1c was 6.6%. “An astounding 95% were current continuous glucose monitoring [CGM] users,” said Ms. Li, a statistician at the Jaeb Center for Health Research in Tampa, Fla.

A total of 398 participants reported at least one exercise day and one sedentary day, for a total of 1,302 exercise days and 2,470 sedentary days.

Overall, the mean TIR was significantly higher on exercise days compared to sedentary days (75% vs. 70%, P < .001). The median time above 180 mg/dL also was significantly lower on exercise days compared to sedentary days (17% vs. 23%, P < .001), and mean glucose levels were 10 mg/dL lower on exercise days (145 mg/dL vs. 155 mg/dL)

“This all came with a slight hit to their time below range,” Ms. Li noted. The median time below 70 mg/dL was 1.1% on exercise days compared to 0.4% on sedentary days (P < .001). The percentage of days with hypoglycemic events was higher on exercise days compared to sedentary days (47% vs. 40%, P < .001), as they are related to time below 70 mg/dL, she added.

The differences for mean glucose level and TIR between exercise days and sedentary days were significant for each of the three exercise types, Ms. Li said.

“After establishing these glycemic trends, we looked at whether there were any factors that influenced the glycemic differences on exercise vs. sedentary days,” Ms. Li said.

Regardless of exercise type, age, sex, baseline A1c, diabetes duration, body mass index, insulin modality, CGM use, and percentage of time below range in the past 24 hours, there was higher TIR and higher hypoglycemia on exercise days compared to sedentary days.

Although the study was limited in part by the observational design, “with these data, we can better understand the glycemic benefits and disadvantages of exercise in adults with type 1 diabetes,” Ms. Li said.
 

Don’t forget the negative effects of exercise

“It is well known that the three types of exercise can modulate glucose levels. This can be very useful when attempting to reduce excessively high glucose levels, and when encouraging people to engage in frequent, regular, and consistent physical activity and exercise for general cardiovascular pulmonary and musculoskeletal health,” Helena W. Rodbard, MD, an endocrinologist in private practice in Rockville, Md., said in an interview.

“However, it was not known what effects various types of exercise would have on time in range (70-180 mg/dL) and time below range (< 70 mg/dL) measured over a full 24-hour period in people with type 1 diabetes,” said Dr. Rodbard, who was not involved with the study.

“I was surprised to see that the effect of the three different types of exercise were so similar,” Dr. Rodbard noted. “There had been previous reports suggesting that the time course of glucose could be different for these three types of exercise.”

The current study confirms prior knowledge that exercise can help reduce blood glucose, and increase TIR, said Dr. Rodbard. The study shows that TIR increases by roughly 5-7 percentage points (about 1 hour per day) and reduces mean glucose by 9-13 mg/dL irrespective of the three types of exercise,” she said. “There was a suggestion that the risk of increasing hypoglycemia below 70 mg/dL was less likely for resistance exercise than for the interval or aerobic types of exercise,” she noted.

As for additional research, “This study did not address the various ways in which one can mitigate the potentially deleterious effects of exercise, specifically with reference to rates of hypoglycemia, even mild symptomatic biochemical hypoglycemia,” said Dr. Rodbard. “Since the actual amount of time below 70 mg/dL is usually so small (0.3%-0.7% of the 1,440 minutes in the day, or about 5-10 minutes per day on average), it is difficult to measure and there is considerable variability between different people,” she emphasized. “Finding optimal and robust ways to achieve consistency in the reduction of glucose, between days within subjects, and between subjects, will need further examination of various types of protocols for diet, exercise and insulin administration, and of various methods for education of the patient,” she said.

The study was supported in part by the Leona M. and Harry B. Helmsley Charitable Trust. Ms. Li and Dr. Rodbard had no financial conflicts to disclose. Dr. Rodbard serves on the editorial advisory board of Clinical Endocrinology News.

Exposure to per- and polyfluoroalkyl substances (PFAS) – a class of widely used synthetic chemicals dubbed “forever chemicals” – may be a modifiable risk factor for the development of hypertension.

In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.

“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.

The study was published online  in Hypertension.
 

Everywhere and forever

“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.

Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.

“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.

For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.

During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.

Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).

Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.

The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).

“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.

They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.

“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.

“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.

The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.

“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
 

‘The more we learn, the worse it gets’

This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.

“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.

“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.

Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”

“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.

The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.

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

Exposure to per- and polyfluoroalkyl substances (PFAS) – a class of widely used synthetic chemicals dubbed “forever chemicals” – may be a modifiable risk factor for the development of hypertension.

In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.

“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.

The study was published online  in Hypertension.
 

Everywhere and forever

“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.

Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.

“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.

For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.

During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.

Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).

Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.

The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).

“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.

They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.

“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.

“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.

The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.

“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
 

‘The more we learn, the worse it gets’

This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.

“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.

“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.

Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”

“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.

The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.

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

Exposure to per- and polyfluoroalkyl substances (PFAS) – a class of widely used synthetic chemicals dubbed “forever chemicals” – may be a modifiable risk factor for the development of hypertension.

In a large, prospective study, researchers found an association between higher blood levels of PFAS and increased risk of hypertension in middle-aged women. Women in the highest tertile of overall PFAS concentrations had a 71% increased risk of developing hypertension.

“Our findings suggest that long-term cumulative exposure, even before midlife, may increase the risk of high blood pressure, and therefore, the benefit of reducing the population exposure to PFAS and potential prevention of high blood pressure and other health conditions would be enormous,” Sung Kyun Park, ScD, MPH, University of Michigan School of Public Health, Ann Arbor, said in an interview.

The study was published online  in Hypertension.
 

Everywhere and forever

“PFAS are forever chemicals as well as everywhere chemicals,” Dr. Park noted.

Possible sources of PFAS exposure run the gamut from nonstick cookware, food wrappers, and waterproof fabrics to cosmetics and drinking water. They have been detected in the blood of most people and have been linked to a variety of health concerns.

“A few studies showed an association between PFAS and hypertension, but those were cross-sectional and examined prevalence of hypertension. It was unclear whether PFAS are associated with the development (incidence) of hypertension,” Dr. Park explained.

For their study, the researchers examined the association between serum concentrations of PFAS and risks of incident hypertension in 1,058 initially normotensive women participating in the Study of Women’s Health Across the Nation-Multi-Pollutant Study (SWAN-MPS). They were followed annually between 1999 and 2017.

During 11,722 person-years of follow-up, 470 of the women developed hypertension, at a rate of 40.1 cases per 1,000 person-years. Hypertension was defined as blood pressure of at least 140 mm Hg systolic or at least 90 mm Hg diastolic or receiving antihypertensive treatment.

Women in the highest tertile of baseline serum concentration of perfluorooctane sulfonate (PFOS) had a 42% higher risk of developing hypertension, compared with peers in the lowest tertile (adjusted hazard ratio, 1.42; 95% confidence interval, 1.19-1.68; P trend = .01).

Similar results were found for perfluorooctanoate (PFOA) and 2-N-ethyl-perfluorooctane sulfonamido acetate (EtFOSAA), with 47% (aHR, 1.47; 95% CI, 1.24-1.75; P trend = .01) and 42% (aHR, 1.42; 95% CI, 1.19-1.70; P trend = .01) higher risks of incident hypertension, comparing the highest to the lowest tertiles.

The risks persisted after adjusting for various factors, including race, study site, education, financial strain, smoking status, alcohol use, total calorie intake, and menopausal status.

In the PFAS “mixture” analysis, women in the highest tertile of overall PFAS concentrations were 71% more likely to develop hypertension during follow-up, compared with women in the lowest tertile (aHR, 1.71; 95% CI, 1.15-2.54; P trend = .008).

“These findings suggest that PFAS might be an underappreciated contributing factor to women’s cardiovascular disease risk,” the researchers write.

They caution that the study only included middle-aged women and that it is unclear whether the findings hold for middle-aged men.

“This is an important question, but the answer is that we do not know,” Dr. Park told this news organization.

“Women become more susceptible to metabolic changes and hypertension risk during the menopausal transition. Our findings suggest that PFAS may play a role in the development of hypertension in women during this critical life stage,” Dr. Park said.

The researchers say more research is needed to confirm and expand the findings and to find ways to reduce PFAS exposure.

“If confirmed in future studies, these findings suggest that understanding human exposure to PFAS and developing effective strategies to reduce PFAS exposure may help prevent the development of hypertension and thereby reduce the global burden of CVD,” the researchers write.
 

‘The more we learn, the worse it gets’

This is an “interesting” study and shows that “the more we learn about PFAS, the worse it seems to get,” Ankur Shah, MD, division of kidney disease and hypertension, Warren Alpert Medical School of Brown University, Providence, R.I., said in an interview.

“This multisite, multiracial and multiethnic, community-based longitudinal study establishes an association between PFAS and hypertension,” said Dr. Shah, who wasn’t involved in the study.

“This adds to a growing literature base of associations of PFAS with illnesses, including malignancy, thyroid disorders, diabetes, ulcerative colitis, hyperlipidemia, and pregnancy-induced hypertension,” he noted.

Dr. Shah also noted that the authors adjusted for race and ethnicity, study site, education, financial strain, smoking status, environmental tobacco smoke, alcohol consumption, total calorie intake, and menopausal status “and still found a strong association.”

“Still to be determined are both whether PFAS are the causative agent or if there is an unmeasured/unadjusted for entity which has resulted in both increased PFAS exposure and hypertension, as well as if PFAS are causative, if reduction in PFAS exposure would be result in blood pressure reduction,” Dr. Shah added.

The study had no sources of funding. Dr. Park and Dr. Shah have disclosed no relevant financial relationships.

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