BUENOS AIRES – Antimicrobial resistance (AMR) has become a global concern. And while one issue to be addressed is the deficit in research and development for new antibiotics, efforts to tackle this public health threat also should be directed toward promoting more rational prescription practices and strengthening the ability to identify the microorganisms responsible for infections, according to the World Health Organization. This was the conclusion reached at the fourth meeting of the WHO AMR Surveillance and Quality Assessment Collaborating Centres Network, which was held in Buenos Aires.

“We have to provide assistance to countries to ensure that the drugs are being used responsibly. We can come up with new antibiotics, but the issue at hand is not simply one of innovation: If nothing is done to correct inappropriate prescription practices and to overcome the lack of diagnostic laboratories at the country level, we’re going to miss out on those drugs as soon as they become available,” Kitty van Weezenbeek, MD, PhD, MPH, director of the AMR Surveillance, Prevention, and Control (AMR/SPC) Department at the WHO’s headquarters in Geneva, told this news organization.

Dr. van Weezenbeek pointed out that although there are currently no shortages of antimicrobials, the development and launch of new drugs that fight multidrug-resistant infections – infections for which there are few therapeutic options – has proceeded slowly. “It takes 10 to 15 years to develop a new antibiotic,” she said, adding that “the majority of pharmaceutical companies that had been engaged in the development of antimicrobials have filed for bankruptcy.”

In 2019, more people died – 1.2 million – from AMR than from malaria, tuberculosis, and HIV combined. Why are there so few market incentives when there is such a great need for those drugs? “One reason is that the pharmaceutical industry makes more money with long-term treatments, such as those for cancer and respiratory diseases. The other problem is that people everywhere are told not to use antibiotics,” said Dr. van Weezenbeek.

“A course of antibiotics lasts a few days, especially because we’re promoting rational use. Therefore, the trend is for the total amount of antimicrobials being used to be lower. So, it’s not as profitable,” added Carmem Lucia Pessoa-Silva, MD, PhD, head of the Surveillance, Evidence, and Laboratory Strengthening Unit of the WHO’s AMR/SPC Department.

On that note, Dr. van Weezenbeek mentioned that member countries are working with pharmaceutical companies and universities to address this problem. The WHO, for its part, has responded by implementing a global mechanism with a public health approach to create a “healthy” and equitable market for these medicines.

AMR is one of the top 10 global threats to human health. But it also has an impact on animal production, agricultural production, and the environment. Strategies to tackle AMR based on the One Health approach should involve all actors, social sectors, and citizens, according to Eva Jané Llopis, PhD, the representative of the Pan American Health Organization/WHO in Argentina.

At the root of the AMR problem is the widespread use of these drugs as growth promoters in animal production – for which several countries have enacted regulations – as well as “misunderstandings” between patients and physicians when there is not sufficient, timely access to laboratory diagnostics, especially in low- and middle-income countries.

“People think that if they’re given broad-spectrum antibiotics, they’re being prescribed the best antibiotics; and doctors, because there are no laboratory services, prescribe broad-spectrum antibiotics because they want to help patients. But that ends up causing more resistance to drugs, and thus, those antibiotics aren’t good for the patients,” said Dr. van Weezenbeek.

The WHO Global AMR and Use Surveillance System (GLASS) was launched in 2015. Its 2022 report, which marked the end of the system’s early implementation period, noted that the reported AMR rates are often lower in countries, territories, and areas with better testing coverage for most pathogen-drug-infection site combinations. However, as Dr. Pessoa-Silva acknowledged, monitoring “has not yet generated representative data,” because in many cases, countries either do not have surveillance systems or have only recently started implementing them.

Even so, the indicators that are available paint an increasingly worrisome picture. “For example, in many countries, resistance rates to first-line antibiotics were around 10%-20% with respect to Escherichia coli urinary tract infections and bloodstream bacteriologically confirmed infections. So, the risk of treatment failure is very high,” explained Dr. Pessoa-Silva.

The latest estimates indicate that every 2 or 3 minutes, somewhere in the world, a child dies from AMR. And the situation is particularly “dramatic” in neonatal intensive care units, where outbreaks of multidrug-resistant infections have a mortality rate of 50%, said Pilar Ramón-Pardo, MD, PhD, lead of the Special Program on AMR at the Pan American Health Organization, the WHO Regional Office for the Americas.

AMR rates also got worse during the pandemic because of the inappropriate prescription of massive amounts of antibiotics to hospitalized patients – something that was not in compliance with guidelines or protocols. Silvia Bertagnolio, MD, is an infectious disease specialist and the head of the Control and Response Strategies Unit in the WHO’s AMR Division. She spoke about the global clinical platform data pertaining to more than 1,500,000 patients who were hospitalized for COVID-19. Since 2020, 85% received antimicrobial treatment, despite the fact that only 5% had a concomitant infection at admission. “It’s easier to give antibiotics than to make a proper diagnosis,” said Dr. Bertagnolio.

This article was translated from Medscape’s Spanish edition and a version appeared on Medscape.com.

BUENOS AIRES – Antimicrobial resistance (AMR) has become a global concern. And while one issue to be addressed is the deficit in research and development for new antibiotics, efforts to tackle this public health threat also should be directed toward promoting more rational prescription practices and strengthening the ability to identify the microorganisms responsible for infections, according to the World Health Organization. This was the conclusion reached at the fourth meeting of the WHO AMR Surveillance and Quality Assessment Collaborating Centres Network, which was held in Buenos Aires.

“We have to provide assistance to countries to ensure that the drugs are being used responsibly. We can come up with new antibiotics, but the issue at hand is not simply one of innovation: If nothing is done to correct inappropriate prescription practices and to overcome the lack of diagnostic laboratories at the country level, we’re going to miss out on those drugs as soon as they become available,” Kitty van Weezenbeek, MD, PhD, MPH, director of the AMR Surveillance, Prevention, and Control (AMR/SPC) Department at the WHO’s headquarters in Geneva, told this news organization.

Dr. van Weezenbeek pointed out that although there are currently no shortages of antimicrobials, the development and launch of new drugs that fight multidrug-resistant infections – infections for which there are few therapeutic options – has proceeded slowly. “It takes 10 to 15 years to develop a new antibiotic,” she said, adding that “the majority of pharmaceutical companies that had been engaged in the development of antimicrobials have filed for bankruptcy.”

In 2019, more people died – 1.2 million – from AMR than from malaria, tuberculosis, and HIV combined. Why are there so few market incentives when there is such a great need for those drugs? “One reason is that the pharmaceutical industry makes more money with long-term treatments, such as those for cancer and respiratory diseases. The other problem is that people everywhere are told not to use antibiotics,” said Dr. van Weezenbeek.

“A course of antibiotics lasts a few days, especially because we’re promoting rational use. Therefore, the trend is for the total amount of antimicrobials being used to be lower. So, it’s not as profitable,” added Carmem Lucia Pessoa-Silva, MD, PhD, head of the Surveillance, Evidence, and Laboratory Strengthening Unit of the WHO’s AMR/SPC Department.

On that note, Dr. van Weezenbeek mentioned that member countries are working with pharmaceutical companies and universities to address this problem. The WHO, for its part, has responded by implementing a global mechanism with a public health approach to create a “healthy” and equitable market for these medicines.

AMR is one of the top 10 global threats to human health. But it also has an impact on animal production, agricultural production, and the environment. Strategies to tackle AMR based on the One Health approach should involve all actors, social sectors, and citizens, according to Eva Jané Llopis, PhD, the representative of the Pan American Health Organization/WHO in Argentina.

At the root of the AMR problem is the widespread use of these drugs as growth promoters in animal production – for which several countries have enacted regulations – as well as “misunderstandings” between patients and physicians when there is not sufficient, timely access to laboratory diagnostics, especially in low- and middle-income countries.

“People think that if they’re given broad-spectrum antibiotics, they’re being prescribed the best antibiotics; and doctors, because there are no laboratory services, prescribe broad-spectrum antibiotics because they want to help patients. But that ends up causing more resistance to drugs, and thus, those antibiotics aren’t good for the patients,” said Dr. van Weezenbeek.

The WHO Global AMR and Use Surveillance System (GLASS) was launched in 2015. Its 2022 report, which marked the end of the system’s early implementation period, noted that the reported AMR rates are often lower in countries, territories, and areas with better testing coverage for most pathogen-drug-infection site combinations. However, as Dr. Pessoa-Silva acknowledged, monitoring “has not yet generated representative data,” because in many cases, countries either do not have surveillance systems or have only recently started implementing them.

Even so, the indicators that are available paint an increasingly worrisome picture. “For example, in many countries, resistance rates to first-line antibiotics were around 10%-20% with respect to Escherichia coli urinary tract infections and bloodstream bacteriologically confirmed infections. So, the risk of treatment failure is very high,” explained Dr. Pessoa-Silva.

The latest estimates indicate that every 2 or 3 minutes, somewhere in the world, a child dies from AMR. And the situation is particularly “dramatic” in neonatal intensive care units, where outbreaks of multidrug-resistant infections have a mortality rate of 50%, said Pilar Ramón-Pardo, MD, PhD, lead of the Special Program on AMR at the Pan American Health Organization, the WHO Regional Office for the Americas.

AMR rates also got worse during the pandemic because of the inappropriate prescription of massive amounts of antibiotics to hospitalized patients – something that was not in compliance with guidelines or protocols. Silvia Bertagnolio, MD, is an infectious disease specialist and the head of the Control and Response Strategies Unit in the WHO’s AMR Division. She spoke about the global clinical platform data pertaining to more than 1,500,000 patients who were hospitalized for COVID-19. Since 2020, 85% received antimicrobial treatment, despite the fact that only 5% had a concomitant infection at admission. “It’s easier to give antibiotics than to make a proper diagnosis,” said Dr. Bertagnolio.

This article was translated from Medscape’s Spanish edition and a version appeared on Medscape.com.

BUENOS AIRES – Antimicrobial resistance (AMR) has become a global concern. And while one issue to be addressed is the deficit in research and development for new antibiotics, efforts to tackle this public health threat also should be directed toward promoting more rational prescription practices and strengthening the ability to identify the microorganisms responsible for infections, according to the World Health Organization. This was the conclusion reached at the fourth meeting of the WHO AMR Surveillance and Quality Assessment Collaborating Centres Network, which was held in Buenos Aires.

“We have to provide assistance to countries to ensure that the drugs are being used responsibly. We can come up with new antibiotics, but the issue at hand is not simply one of innovation: If nothing is done to correct inappropriate prescription practices and to overcome the lack of diagnostic laboratories at the country level, we’re going to miss out on those drugs as soon as they become available,” Kitty van Weezenbeek, MD, PhD, MPH, director of the AMR Surveillance, Prevention, and Control (AMR/SPC) Department at the WHO’s headquarters in Geneva, told this news organization.

Dr. van Weezenbeek pointed out that although there are currently no shortages of antimicrobials, the development and launch of new drugs that fight multidrug-resistant infections – infections for which there are few therapeutic options – has proceeded slowly. “It takes 10 to 15 years to develop a new antibiotic,” she said, adding that “the majority of pharmaceutical companies that had been engaged in the development of antimicrobials have filed for bankruptcy.”

In 2019, more people died – 1.2 million – from AMR than from malaria, tuberculosis, and HIV combined. Why are there so few market incentives when there is such a great need for those drugs? “One reason is that the pharmaceutical industry makes more money with long-term treatments, such as those for cancer and respiratory diseases. The other problem is that people everywhere are told not to use antibiotics,” said Dr. van Weezenbeek.

“A course of antibiotics lasts a few days, especially because we’re promoting rational use. Therefore, the trend is for the total amount of antimicrobials being used to be lower. So, it’s not as profitable,” added Carmem Lucia Pessoa-Silva, MD, PhD, head of the Surveillance, Evidence, and Laboratory Strengthening Unit of the WHO’s AMR/SPC Department.

On that note, Dr. van Weezenbeek mentioned that member countries are working with pharmaceutical companies and universities to address this problem. The WHO, for its part, has responded by implementing a global mechanism with a public health approach to create a “healthy” and equitable market for these medicines.

AMR is one of the top 10 global threats to human health. But it also has an impact on animal production, agricultural production, and the environment. Strategies to tackle AMR based on the One Health approach should involve all actors, social sectors, and citizens, according to Eva Jané Llopis, PhD, the representative of the Pan American Health Organization/WHO in Argentina.

At the root of the AMR problem is the widespread use of these drugs as growth promoters in animal production – for which several countries have enacted regulations – as well as “misunderstandings” between patients and physicians when there is not sufficient, timely access to laboratory diagnostics, especially in low- and middle-income countries.

“People think that if they’re given broad-spectrum antibiotics, they’re being prescribed the best antibiotics; and doctors, because there are no laboratory services, prescribe broad-spectrum antibiotics because they want to help patients. But that ends up causing more resistance to drugs, and thus, those antibiotics aren’t good for the patients,” said Dr. van Weezenbeek.

The WHO Global AMR and Use Surveillance System (GLASS) was launched in 2015. Its 2022 report, which marked the end of the system’s early implementation period, noted that the reported AMR rates are often lower in countries, territories, and areas with better testing coverage for most pathogen-drug-infection site combinations. However, as Dr. Pessoa-Silva acknowledged, monitoring “has not yet generated representative data,” because in many cases, countries either do not have surveillance systems or have only recently started implementing them.

Even so, the indicators that are available paint an increasingly worrisome picture. “For example, in many countries, resistance rates to first-line antibiotics were around 10%-20% with respect to Escherichia coli urinary tract infections and bloodstream bacteriologically confirmed infections. So, the risk of treatment failure is very high,” explained Dr. Pessoa-Silva.

The latest estimates indicate that every 2 or 3 minutes, somewhere in the world, a child dies from AMR. And the situation is particularly “dramatic” in neonatal intensive care units, where outbreaks of multidrug-resistant infections have a mortality rate of 50%, said Pilar Ramón-Pardo, MD, PhD, lead of the Special Program on AMR at the Pan American Health Organization, the WHO Regional Office for the Americas.

AMR rates also got worse during the pandemic because of the inappropriate prescription of massive amounts of antibiotics to hospitalized patients – something that was not in compliance with guidelines or protocols. Silvia Bertagnolio, MD, is an infectious disease specialist and the head of the Control and Response Strategies Unit in the WHO’s AMR Division. She spoke about the global clinical platform data pertaining to more than 1,500,000 patients who were hospitalized for COVID-19. Since 2020, 85% received antimicrobial treatment, despite the fact that only 5% had a concomitant infection at admission. “It’s easier to give antibiotics than to make a proper diagnosis,” said Dr. Bertagnolio.

This article was translated from Medscape’s Spanish edition and a version appeared on Medscape.com.

A new federal rule seeks to reduce Medicare Advantage insurance plans’ prior authorization burdens on physicians while also ensuring that enrollees have the same access to necessary care that they would receive under traditional fee-for-service Medicare.

The prior authorization changes, announced this week, are part of the Centers for Medicare & Medicaid Services’ 2024 update of policy changes for Medicare Advantage and Part D pharmacy plans

Medicare Advantage plans’ business practices have raised significant concerns in recent years. More than 28 million Americans were enrolled in a Medicare Advantage plan in 2022, which is nearly half of all Medicare enrollees, according to the Kaiser Family Foundation.

Medicare pays a fixed amount per enrollee per year to these privately run managed care plans, in contrast to traditional fee-for-service Medicare. Medicare Advantage plans have been criticized for aggressive marketing, for overbilling the federal government for care, and for using prior authorization to inappropriately deny needed care to patients.

About 13% of prior authorization requests that are denied by Medicare Advantage plans actually met Medicare coverage rules and should have been approved, the Office of the Inspector General at the U.S. Department of Health & Human Services reported in 2022.

The newly finalized rule now requires Medicare Advantage plans to do the following.

• Ensure that a prior authorization approval, once granted, remains valid for as long as medically necessary to avoid disruptions in care.
• Conduct an annual review of utilization management policies.
• Ensure that coverage denials based on medical necessity be reviewed by health care professionals with relevant expertise before a denial can be issued.

Physician groups welcomed the changes. In a statement, the American Medical Association said that an initial reading of the rule suggested CMS had “taken important steps toward right-sizing the prior authorization process.”

The Medical Group Management Association praised CMS in a statement for having limited “dangerous disruptions and delays to necessary patient care” resulting from the cumbersome processes of prior approval. With the new rules, CMS will provide greater consistency across Advantage plans as well as traditional Medicare, said Anders Gilberg, MGMA’s senior vice president of government affairs, in a statement.
 

Peer consideration

The final rule did disappoint physician groups in one key way. CMS rebuffed requests to have CMS require Advantage plans to use reviewers of the same specialty as treating physicians in handling disputes about prior authorization. CMS said it expects plans to exercise judgment in finding reviewers with “sufficient expertise to make an informed and supportable decision.”

“In some instances, we expect that plans will use a physician or other health care professional of the same specialty or subspecialty as the treating physician,” CMS said. “In other instances, we expect that plans will utilize a reviewer with specialized training, certification, or clinical experience in the applicable field of medicine.”
 

Medicare Advantage marketing ‘sowing confusion’

With this final rule, CMS also sought to protect consumers from “potentially misleading marketing practices” used in promoting Medicare Advantage and Part D prescription drug plans.

The agency said it had received complaints about people who have received official-looking promotional materials for Medicare that directed them not to government sources of information but to Medicare Advantage and Part D plans or their agents and brokers.

Ads now must mention a specific plan name, and they cannot use the Medicare name, CMS logo, Medicare card, or other government information in a misleading way, CMS said.

“CMS can see no value or purpose in a non-governmental entity’s use of the Medicare logo or HHS logo except for the express purpose of sowing confusion and misrepresenting itself as the government,” the agency said.

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

A new federal rule seeks to reduce Medicare Advantage insurance plans’ prior authorization burdens on physicians while also ensuring that enrollees have the same access to necessary care that they would receive under traditional fee-for-service Medicare.

The prior authorization changes, announced this week, are part of the Centers for Medicare & Medicaid Services’ 2024 update of policy changes for Medicare Advantage and Part D pharmacy plans

Medicare Advantage plans’ business practices have raised significant concerns in recent years. More than 28 million Americans were enrolled in a Medicare Advantage plan in 2022, which is nearly half of all Medicare enrollees, according to the Kaiser Family Foundation.

Medicare pays a fixed amount per enrollee per year to these privately run managed care plans, in contrast to traditional fee-for-service Medicare. Medicare Advantage plans have been criticized for aggressive marketing, for overbilling the federal government for care, and for using prior authorization to inappropriately deny needed care to patients.

About 13% of prior authorization requests that are denied by Medicare Advantage plans actually met Medicare coverage rules and should have been approved, the Office of the Inspector General at the U.S. Department of Health & Human Services reported in 2022.

The newly finalized rule now requires Medicare Advantage plans to do the following.

• Ensure that a prior authorization approval, once granted, remains valid for as long as medically necessary to avoid disruptions in care.
• Conduct an annual review of utilization management policies.
• Ensure that coverage denials based on medical necessity be reviewed by health care professionals with relevant expertise before a denial can be issued.

Physician groups welcomed the changes. In a statement, the American Medical Association said that an initial reading of the rule suggested CMS had “taken important steps toward right-sizing the prior authorization process.”

The Medical Group Management Association praised CMS in a statement for having limited “dangerous disruptions and delays to necessary patient care” resulting from the cumbersome processes of prior approval. With the new rules, CMS will provide greater consistency across Advantage plans as well as traditional Medicare, said Anders Gilberg, MGMA’s senior vice president of government affairs, in a statement.
 

Peer consideration

The final rule did disappoint physician groups in one key way. CMS rebuffed requests to have CMS require Advantage plans to use reviewers of the same specialty as treating physicians in handling disputes about prior authorization. CMS said it expects plans to exercise judgment in finding reviewers with “sufficient expertise to make an informed and supportable decision.”

“In some instances, we expect that plans will use a physician or other health care professional of the same specialty or subspecialty as the treating physician,” CMS said. “In other instances, we expect that plans will utilize a reviewer with specialized training, certification, or clinical experience in the applicable field of medicine.”
 

Medicare Advantage marketing ‘sowing confusion’

With this final rule, CMS also sought to protect consumers from “potentially misleading marketing practices” used in promoting Medicare Advantage and Part D prescription drug plans.

The agency said it had received complaints about people who have received official-looking promotional materials for Medicare that directed them not to government sources of information but to Medicare Advantage and Part D plans or their agents and brokers.

Ads now must mention a specific plan name, and they cannot use the Medicare name, CMS logo, Medicare card, or other government information in a misleading way, CMS said.

“CMS can see no value or purpose in a non-governmental entity’s use of the Medicare logo or HHS logo except for the express purpose of sowing confusion and misrepresenting itself as the government,” the agency said.

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

A new federal rule seeks to reduce Medicare Advantage insurance plans’ prior authorization burdens on physicians while also ensuring that enrollees have the same access to necessary care that they would receive under traditional fee-for-service Medicare.

The prior authorization changes, announced this week, are part of the Centers for Medicare & Medicaid Services’ 2024 update of policy changes for Medicare Advantage and Part D pharmacy plans

Medicare Advantage plans’ business practices have raised significant concerns in recent years. More than 28 million Americans were enrolled in a Medicare Advantage plan in 2022, which is nearly half of all Medicare enrollees, according to the Kaiser Family Foundation.

Medicare pays a fixed amount per enrollee per year to these privately run managed care plans, in contrast to traditional fee-for-service Medicare. Medicare Advantage plans have been criticized for aggressive marketing, for overbilling the federal government for care, and for using prior authorization to inappropriately deny needed care to patients.

About 13% of prior authorization requests that are denied by Medicare Advantage plans actually met Medicare coverage rules and should have been approved, the Office of the Inspector General at the U.S. Department of Health & Human Services reported in 2022.

The newly finalized rule now requires Medicare Advantage plans to do the following.

• Ensure that a prior authorization approval, once granted, remains valid for as long as medically necessary to avoid disruptions in care.
• Conduct an annual review of utilization management policies.
• Ensure that coverage denials based on medical necessity be reviewed by health care professionals with relevant expertise before a denial can be issued.

Physician groups welcomed the changes. In a statement, the American Medical Association said that an initial reading of the rule suggested CMS had “taken important steps toward right-sizing the prior authorization process.”

The Medical Group Management Association praised CMS in a statement for having limited “dangerous disruptions and delays to necessary patient care” resulting from the cumbersome processes of prior approval. With the new rules, CMS will provide greater consistency across Advantage plans as well as traditional Medicare, said Anders Gilberg, MGMA’s senior vice president of government affairs, in a statement.
 

Peer consideration

The final rule did disappoint physician groups in one key way. CMS rebuffed requests to have CMS require Advantage plans to use reviewers of the same specialty as treating physicians in handling disputes about prior authorization. CMS said it expects plans to exercise judgment in finding reviewers with “sufficient expertise to make an informed and supportable decision.”

“In some instances, we expect that plans will use a physician or other health care professional of the same specialty or subspecialty as the treating physician,” CMS said. “In other instances, we expect that plans will utilize a reviewer with specialized training, certification, or clinical experience in the applicable field of medicine.”
 

Medicare Advantage marketing ‘sowing confusion’

With this final rule, CMS also sought to protect consumers from “potentially misleading marketing practices” used in promoting Medicare Advantage and Part D prescription drug plans.

The agency said it had received complaints about people who have received official-looking promotional materials for Medicare that directed them not to government sources of information but to Medicare Advantage and Part D plans or their agents and brokers.

Ads now must mention a specific plan name, and they cannot use the Medicare name, CMS logo, Medicare card, or other government information in a misleading way, CMS said.

“CMS can see no value or purpose in a non-governmental entity’s use of the Medicare logo or HHS logo except for the express purpose of sowing confusion and misrepresenting itself as the government,” the agency said.

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

In this video Naresh Gunaratnam, MD, discusses the gastroenterology fellowship program that Huron Gastroenterology developed with Trinity Health in Ann Arbor, Mich. Dr. Gunaratnam helped create the program because he and his colleagues felt that traditional fellowship programs don’t always provide information or guidance about non-academic career pathways in gastroenterology. Hear from Dr. Gunaratnam how the fellowship program at Huron Gastroenterology is training fellows to become excellent clinicians who care for patients in the community setting. He has no financial conflicts relative to the topics in this video.

Vidyard Video

In this video Naresh Gunaratnam, MD, discusses the gastroenterology fellowship program that Huron Gastroenterology developed with Trinity Health in Ann Arbor, Mich. Dr. Gunaratnam helped create the program because he and his colleagues felt that traditional fellowship programs don’t always provide information or guidance about non-academic career pathways in gastroenterology. Hear from Dr. Gunaratnam how the fellowship program at Huron Gastroenterology is training fellows to become excellent clinicians who care for patients in the community setting. He has no financial conflicts relative to the topics in this video.

Vidyard Video

In this video Naresh Gunaratnam, MD, discusses the gastroenterology fellowship program that Huron Gastroenterology developed with Trinity Health in Ann Arbor, Mich. Dr. Gunaratnam helped create the program because he and his colleagues felt that traditional fellowship programs don’t always provide information or guidance about non-academic career pathways in gastroenterology. Hear from Dr. Gunaratnam how the fellowship program at Huron Gastroenterology is training fellows to become excellent clinicians who care for patients in the community setting. He has no financial conflicts relative to the topics in this video.

Vidyard Video

With more than 306 million views, #hormonebalance and #hormonebalancing are among the latest hacks to take over the social media platform TikTok, on which users post short videos. Influencers offer advice such as eating raw carrots for “happy hormones,” eating protein followed by fat for breakfast to regulate blood glucose, or taking vitamin B2 supplements for thyroid health.

Have you ever wondered if you were asleep during the lecture on “hormone balancing” in medical school? No, you weren’t. It was never a class for good reason, and you didn’t fail to read any such breakthrough studies in The New England Journal of Medicine either.

Although the sound bites no doubt garner attention among TikTok users, “hormone balancing” is a fictional term that is practically meaningless.

There are over 50 different hormones produced by humans and animals, regulating sleep, growth, metabolism and reproduction, among many other biological processes, so there is certainly no one-size-fits-all solution to ensure these are all working in perfect harmony.

When someone mentions “hormone balancing,” my mind wanders to the last time I took my car to have my tires rotated and balanced. If only it were as simple to balance hormones in real life. The best we can hope for is to get a specific hormone within the ideal physiologic range for that person’s age.

The term “hormone” can mean many things to different people. When a woman comes in with a hormone question, for example, it is often related to estrogen, followed by thyroid hormones. A wealth of misinformation exists in popular literature regarding these hormones alone.

Estrogen can be replaced, but not everyone needs it replaced. It depends on variables including age, underlying medical conditions, the time of day a test was drawn, and concomitant medications. Having low levels of a given hormone does not necessarily call for replacement either.

Insulin is another example of a hormone that can never completely be replaced in people with diabetes in a way that exactly mimics the normal physiologic release.

There are many lesser-known hormones that are measurable and replaceable but are also more difficult to reset to original manufacturer specifications.

A Google search for “hormone balancing” often sends you to “naturopaths” or “integrative medicine” practitioners, who often propose similar solutions to the TikTok influencers. Users are told that their hormones are out of whack and that restoring this “balance” can be achieved by purchasing whatever “natural products” or concoction they are selling.

These TikTok videos and online “experts” are the home-brewed versions of the strip-mall hormone specialists. TikTok videos claiming to help “balance hormones” typically don’t name a specific hormone either, or the end organs that each would have an impact on. Rather, they lump all hormones into a monolithic entity, implying that there is a single solution for all health problems. And personal testimonials extolling the benefits of a TikTok intervention don’t constitute proof of efficacy no matter how many “likes” they get. These influencers assume that viewers can “sense” their hormones are out of tune and no lab tests can convince them otherwise.

In these inflationary times, the cost of seeking medical care from conventional channels is increasingly prohibitive. It’s easy to understand the appeal of getting free advice from TikTok or some other Internet site. At best, following the advice will not have much impact; at worst, it could be harmful.
 

Don’t try this at home

There are some things that should never be tried at home, and do-it-yourself hormone replacement or remediation both fall under this umbrella.

Generally, the body does a good job of balancing its own hormones. Most patients don’t need to be worried if they’re in good health. If they’re in doubt, they should seek advice from a doctor, ideally an endocrinologist, but an ob.gyn. or general practitioner are also good options.

One of the first questions to ask a patient is “Which hormone are you worried about?” or “What health issue is it specifically that is bothering you?” Narrowing the focus to a single thing, if possible, will lead to a more efficient evaluation.

Often, patients arrive with multiple concerns written on little pieces of paper. These ubiquitous pieces of paper are the red flag for the flood of questions to follow.

Ordering the appropriate tests for the conditions they are concerned about can help put their minds at ease. If there are any specific deficiencies, or excesses in any hormones, then appropriate solutions can be discussed.

TikTok hormone-balancing solutions are simply the 21st-century version of the snake oil sold on late-night cable TV in the 1990s.

Needless to say, you should gently encourage your patients to stay away from these non–FDA-approved products, without making them feel stupid. Off-label use of hormones when these are not indicated is also to be avoided, unless a medical practitioner feels it is warranted.

Dr. de la Rosa is an endocrinologist in Englewood, Fla. He disclosed no conflicts of interest.

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

With more than 306 million views, #hormonebalance and #hormonebalancing are among the latest hacks to take over the social media platform TikTok, on which users post short videos. Influencers offer advice such as eating raw carrots for “happy hormones,” eating protein followed by fat for breakfast to regulate blood glucose, or taking vitamin B2 supplements for thyroid health.

Have you ever wondered if you were asleep during the lecture on “hormone balancing” in medical school? No, you weren’t. It was never a class for good reason, and you didn’t fail to read any such breakthrough studies in The New England Journal of Medicine either.

Although the sound bites no doubt garner attention among TikTok users, “hormone balancing” is a fictional term that is practically meaningless.

There are over 50 different hormones produced by humans and animals, regulating sleep, growth, metabolism and reproduction, among many other biological processes, so there is certainly no one-size-fits-all solution to ensure these are all working in perfect harmony.

When someone mentions “hormone balancing,” my mind wanders to the last time I took my car to have my tires rotated and balanced. If only it were as simple to balance hormones in real life. The best we can hope for is to get a specific hormone within the ideal physiologic range for that person’s age.

The term “hormone” can mean many things to different people. When a woman comes in with a hormone question, for example, it is often related to estrogen, followed by thyroid hormones. A wealth of misinformation exists in popular literature regarding these hormones alone.

Estrogen can be replaced, but not everyone needs it replaced. It depends on variables including age, underlying medical conditions, the time of day a test was drawn, and concomitant medications. Having low levels of a given hormone does not necessarily call for replacement either.

Insulin is another example of a hormone that can never completely be replaced in people with diabetes in a way that exactly mimics the normal physiologic release.

There are many lesser-known hormones that are measurable and replaceable but are also more difficult to reset to original manufacturer specifications.

A Google search for “hormone balancing” often sends you to “naturopaths” or “integrative medicine” practitioners, who often propose similar solutions to the TikTok influencers. Users are told that their hormones are out of whack and that restoring this “balance” can be achieved by purchasing whatever “natural products” or concoction they are selling.

These TikTok videos and online “experts” are the home-brewed versions of the strip-mall hormone specialists. TikTok videos claiming to help “balance hormones” typically don’t name a specific hormone either, or the end organs that each would have an impact on. Rather, they lump all hormones into a monolithic entity, implying that there is a single solution for all health problems. And personal testimonials extolling the benefits of a TikTok intervention don’t constitute proof of efficacy no matter how many “likes” they get. These influencers assume that viewers can “sense” their hormones are out of tune and no lab tests can convince them otherwise.

In these inflationary times, the cost of seeking medical care from conventional channels is increasingly prohibitive. It’s easy to understand the appeal of getting free advice from TikTok or some other Internet site. At best, following the advice will not have much impact; at worst, it could be harmful.
 

Don’t try this at home

There are some things that should never be tried at home, and do-it-yourself hormone replacement or remediation both fall under this umbrella.

Generally, the body does a good job of balancing its own hormones. Most patients don’t need to be worried if they’re in good health. If they’re in doubt, they should seek advice from a doctor, ideally an endocrinologist, but an ob.gyn. or general practitioner are also good options.

One of the first questions to ask a patient is “Which hormone are you worried about?” or “What health issue is it specifically that is bothering you?” Narrowing the focus to a single thing, if possible, will lead to a more efficient evaluation.

Often, patients arrive with multiple concerns written on little pieces of paper. These ubiquitous pieces of paper are the red flag for the flood of questions to follow.

Ordering the appropriate tests for the conditions they are concerned about can help put their minds at ease. If there are any specific deficiencies, or excesses in any hormones, then appropriate solutions can be discussed.

TikTok hormone-balancing solutions are simply the 21st-century version of the snake oil sold on late-night cable TV in the 1990s.

Needless to say, you should gently encourage your patients to stay away from these non–FDA-approved products, without making them feel stupid. Off-label use of hormones when these are not indicated is also to be avoided, unless a medical practitioner feels it is warranted.

Dr. de la Rosa is an endocrinologist in Englewood, Fla. He disclosed no conflicts of interest.

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

With more than 306 million views, #hormonebalance and #hormonebalancing are among the latest hacks to take over the social media platform TikTok, on which users post short videos. Influencers offer advice such as eating raw carrots for “happy hormones,” eating protein followed by fat for breakfast to regulate blood glucose, or taking vitamin B2 supplements for thyroid health.

Have you ever wondered if you were asleep during the lecture on “hormone balancing” in medical school? No, you weren’t. It was never a class for good reason, and you didn’t fail to read any such breakthrough studies in The New England Journal of Medicine either.

Although the sound bites no doubt garner attention among TikTok users, “hormone balancing” is a fictional term that is practically meaningless.

There are over 50 different hormones produced by humans and animals, regulating sleep, growth, metabolism and reproduction, among many other biological processes, so there is certainly no one-size-fits-all solution to ensure these are all working in perfect harmony.

When someone mentions “hormone balancing,” my mind wanders to the last time I took my car to have my tires rotated and balanced. If only it were as simple to balance hormones in real life. The best we can hope for is to get a specific hormone within the ideal physiologic range for that person’s age.

The term “hormone” can mean many things to different people. When a woman comes in with a hormone question, for example, it is often related to estrogen, followed by thyroid hormones. A wealth of misinformation exists in popular literature regarding these hormones alone.

Estrogen can be replaced, but not everyone needs it replaced. It depends on variables including age, underlying medical conditions, the time of day a test was drawn, and concomitant medications. Having low levels of a given hormone does not necessarily call for replacement either.

Insulin is another example of a hormone that can never completely be replaced in people with diabetes in a way that exactly mimics the normal physiologic release.

There are many lesser-known hormones that are measurable and replaceable but are also more difficult to reset to original manufacturer specifications.

A Google search for “hormone balancing” often sends you to “naturopaths” or “integrative medicine” practitioners, who often propose similar solutions to the TikTok influencers. Users are told that their hormones are out of whack and that restoring this “balance” can be achieved by purchasing whatever “natural products” or concoction they are selling.

These TikTok videos and online “experts” are the home-brewed versions of the strip-mall hormone specialists. TikTok videos claiming to help “balance hormones” typically don’t name a specific hormone either, or the end organs that each would have an impact on. Rather, they lump all hormones into a monolithic entity, implying that there is a single solution for all health problems. And personal testimonials extolling the benefits of a TikTok intervention don’t constitute proof of efficacy no matter how many “likes” they get. These influencers assume that viewers can “sense” their hormones are out of tune and no lab tests can convince them otherwise.

In these inflationary times, the cost of seeking medical care from conventional channels is increasingly prohibitive. It’s easy to understand the appeal of getting free advice from TikTok or some other Internet site. At best, following the advice will not have much impact; at worst, it could be harmful.
 

Don’t try this at home

There are some things that should never be tried at home, and do-it-yourself hormone replacement or remediation both fall under this umbrella.

Generally, the body does a good job of balancing its own hormones. Most patients don’t need to be worried if they’re in good health. If they’re in doubt, they should seek advice from a doctor, ideally an endocrinologist, but an ob.gyn. or general practitioner are also good options.

One of the first questions to ask a patient is “Which hormone are you worried about?” or “What health issue is it specifically that is bothering you?” Narrowing the focus to a single thing, if possible, will lead to a more efficient evaluation.

Often, patients arrive with multiple concerns written on little pieces of paper. These ubiquitous pieces of paper are the red flag for the flood of questions to follow.

Ordering the appropriate tests for the conditions they are concerned about can help put their minds at ease. If there are any specific deficiencies, or excesses in any hormones, then appropriate solutions can be discussed.

TikTok hormone-balancing solutions are simply the 21st-century version of the snake oil sold on late-night cable TV in the 1990s.

Needless to say, you should gently encourage your patients to stay away from these non–FDA-approved products, without making them feel stupid. Off-label use of hormones when these are not indicated is also to be avoided, unless a medical practitioner feels it is warranted.

Dr. de la Rosa is an endocrinologist in Englewood, Fla. He disclosed no conflicts of interest.

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

PARIS – Exercise has a variable impact on the onset of gastroesophageal reflux disease (GERD) symptoms. The mechanisms at play are complex and seldom studied. Frank Zerbib, MD, head of the department of gastroenterology at Bordeaux (France) University Hospital, broke them down during a session dedicated to exercise, which was the common theme of the JFHOD 2023, a French-speaking hepato-gastroenterology and digestive oncology conference held this year in Paris.

A contributing factor

Several factors can affect how exercise causes gastroesophageal reflux.

“Vigorous,” or mainly sports-related, exercise has a detrimental effect on GERD. Approximately 60% of athletes are said to report GERD symptoms connected to an increase in abdominal pressure. This is not because of obesity, but because of the abdominal contraction that occurs during exercise.

Other pathophysiological factors at the root of exercise-induced GERD can be involved in this phenomenon, namely a decrease in lower esophageal sphincter (LES) pressure and esophageal motility, in addition to phases of dissociation between the LES and the diaphragm, which is when most GERD episodes occur.

In such contexts, “it would appear that sports-related exercise has a relatively detrimental effect on the gastroesophageal junction and anti-GERD mechanisms,” said Dr. Zerbib. Meta-analyses provide answers to some questions, but not all; the situation is much less clear when it comes to non–sports-related exercise.”
 

Not so simple

“Taking into account only patients whose GERD has been confirmed through esophageal pH monitoring, exercise does not appear to significantly impact GERD symptoms or the characteristics seen on pH monitoring,” said Dr. Zerbib.

These results come from a study of 100 patients whose exercise level was assessed using the International Physical Activity Questionnaire and expressed using the standard metric of metabolic rate by minutes of performance during a week (METs-minute/week).

This questionnaire is used for most studies that assess exercise and separates patients into three groups (low, moderate, or high) based on their level of exercise. In essence, it considers the duration of exercise but not the type (that is, professional, recreational, and so on) or intensity, resulting in a key methodological issue to consider during the analysis, for example, of the results of a large meta-analysis on the topic.

The meta-analysis in question included 78,000 patients, of whom 10,000 had GERD symptoms.

Based on the results, exercise decreases the risk of GERD by about one-third, after adjustment for body mass index (BMI). “This last point is important,” Dr. Zerbib noted, “since adjusting for BMI without providing the nonadjusted data fails to identify whether exercise decreases the risk of GERD because of the effect on the BMI.* What’s more, when it comes to complications of GERD, like Barrett’s esophagus or adenocarcinoma, the data are far fewer and less robust, with negative case-control studies for the most part.”

One of these two studies, which concerned non–sports-related exercise and the onset of Barrett’s esophagus, reported no association (odds ratio, 1.19; 95% confidence interval, 0.82-1.73).

“Exercise considered vigorous (sports-related) contributes to GERD by altering the antireflux barrier (LES/diaphragm dissociation) and increasing constraints on the esophageal junction (abdominal pressure). In the general population, regular exercise likely decreases the risk of pathological GERD. When it comes to complications of GERD, the data are not very robust, mostly because the studies omitted several exercise-related (healthy lifestyle) factors,” said Dr. Zerbib.
 

Several confounding factors

It’s difficult to issue an opinion under these conditions. There are several confounding factors that studies rarely address. Although the studies always included factors such as age, sex, or BMI, other parameters related to a healthy lifestyle, whether directly or indirectly connected to exercise, were never mentioned. Indeed, diet (such as high calorie or high fat) is known to lead to an increased incidence of GERD. The same goes for alcohol use. Occupation also likely plays a role, but the studies do not mention this.

“So, it’s easy to imagine that a patient who regularly exercises likely eats healthier than a sedentary patient, which comes with the likelihood of a lower risk of developing GERD symptoms,” said Dr. Zerbib. “Overall, evaluating the impact of exercise on GERD is no small feat. It can be said with relative certainty that exercise contributes to GERD through a proven pathophysiology. In the general population, however, exercise likely reduces the risk of GERD but not of its complications. Other than the impact on weight and abdominal obesity, the reality is that a lack of exercise is associated with a less healthy lifestyle and, therefore, behaviors that contribute to GERD.”

Dr. Zerbib reported no conflicts of interest connected to this presentation.

* From a pathophysiological standpoint, the evidence is clear that a high BMI increases the gastroesophageal pressure gradient and dissociation between the LES and the diaphragm, whether temporarily or permanently, as in the case of a hiatal hernia. Abdominal obesity increases constraints on the gastroesophageal junction and results in a two- to threefold increase in the risk of GERD and its complications.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

PARIS – Exercise has a variable impact on the onset of gastroesophageal reflux disease (GERD) symptoms. The mechanisms at play are complex and seldom studied. Frank Zerbib, MD, head of the department of gastroenterology at Bordeaux (France) University Hospital, broke them down during a session dedicated to exercise, which was the common theme of the JFHOD 2023, a French-speaking hepato-gastroenterology and digestive oncology conference held this year in Paris.

A contributing factor

Several factors can affect how exercise causes gastroesophageal reflux.

“Vigorous,” or mainly sports-related, exercise has a detrimental effect on GERD. Approximately 60% of athletes are said to report GERD symptoms connected to an increase in abdominal pressure. This is not because of obesity, but because of the abdominal contraction that occurs during exercise.

Other pathophysiological factors at the root of exercise-induced GERD can be involved in this phenomenon, namely a decrease in lower esophageal sphincter (LES) pressure and esophageal motility, in addition to phases of dissociation between the LES and the diaphragm, which is when most GERD episodes occur.

In such contexts, “it would appear that sports-related exercise has a relatively detrimental effect on the gastroesophageal junction and anti-GERD mechanisms,” said Dr. Zerbib. Meta-analyses provide answers to some questions, but not all; the situation is much less clear when it comes to non–sports-related exercise.”
 

Not so simple

“Taking into account only patients whose GERD has been confirmed through esophageal pH monitoring, exercise does not appear to significantly impact GERD symptoms or the characteristics seen on pH monitoring,” said Dr. Zerbib.

These results come from a study of 100 patients whose exercise level was assessed using the International Physical Activity Questionnaire and expressed using the standard metric of metabolic rate by minutes of performance during a week (METs-minute/week).

This questionnaire is used for most studies that assess exercise and separates patients into three groups (low, moderate, or high) based on their level of exercise. In essence, it considers the duration of exercise but not the type (that is, professional, recreational, and so on) or intensity, resulting in a key methodological issue to consider during the analysis, for example, of the results of a large meta-analysis on the topic.

The meta-analysis in question included 78,000 patients, of whom 10,000 had GERD symptoms.

Based on the results, exercise decreases the risk of GERD by about one-third, after adjustment for body mass index (BMI). “This last point is important,” Dr. Zerbib noted, “since adjusting for BMI without providing the nonadjusted data fails to identify whether exercise decreases the risk of GERD because of the effect on the BMI.* What’s more, when it comes to complications of GERD, like Barrett’s esophagus or adenocarcinoma, the data are far fewer and less robust, with negative case-control studies for the most part.”

One of these two studies, which concerned non–sports-related exercise and the onset of Barrett’s esophagus, reported no association (odds ratio, 1.19; 95% confidence interval, 0.82-1.73).

“Exercise considered vigorous (sports-related) contributes to GERD by altering the antireflux barrier (LES/diaphragm dissociation) and increasing constraints on the esophageal junction (abdominal pressure). In the general population, regular exercise likely decreases the risk of pathological GERD. When it comes to complications of GERD, the data are not very robust, mostly because the studies omitted several exercise-related (healthy lifestyle) factors,” said Dr. Zerbib.
 

Several confounding factors

It’s difficult to issue an opinion under these conditions. There are several confounding factors that studies rarely address. Although the studies always included factors such as age, sex, or BMI, other parameters related to a healthy lifestyle, whether directly or indirectly connected to exercise, were never mentioned. Indeed, diet (such as high calorie or high fat) is known to lead to an increased incidence of GERD. The same goes for alcohol use. Occupation also likely plays a role, but the studies do not mention this.

“So, it’s easy to imagine that a patient who regularly exercises likely eats healthier than a sedentary patient, which comes with the likelihood of a lower risk of developing GERD symptoms,” said Dr. Zerbib. “Overall, evaluating the impact of exercise on GERD is no small feat. It can be said with relative certainty that exercise contributes to GERD through a proven pathophysiology. In the general population, however, exercise likely reduces the risk of GERD but not of its complications. Other than the impact on weight and abdominal obesity, the reality is that a lack of exercise is associated with a less healthy lifestyle and, therefore, behaviors that contribute to GERD.”

Dr. Zerbib reported no conflicts of interest connected to this presentation.

* From a pathophysiological standpoint, the evidence is clear that a high BMI increases the gastroesophageal pressure gradient and dissociation between the LES and the diaphragm, whether temporarily or permanently, as in the case of a hiatal hernia. Abdominal obesity increases constraints on the gastroesophageal junction and results in a two- to threefold increase in the risk of GERD and its complications.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

PARIS – Exercise has a variable impact on the onset of gastroesophageal reflux disease (GERD) symptoms. The mechanisms at play are complex and seldom studied. Frank Zerbib, MD, head of the department of gastroenterology at Bordeaux (France) University Hospital, broke them down during a session dedicated to exercise, which was the common theme of the JFHOD 2023, a French-speaking hepato-gastroenterology and digestive oncology conference held this year in Paris.

A contributing factor

Several factors can affect how exercise causes gastroesophageal reflux.

“Vigorous,” or mainly sports-related, exercise has a detrimental effect on GERD. Approximately 60% of athletes are said to report GERD symptoms connected to an increase in abdominal pressure. This is not because of obesity, but because of the abdominal contraction that occurs during exercise.

Other pathophysiological factors at the root of exercise-induced GERD can be involved in this phenomenon, namely a decrease in lower esophageal sphincter (LES) pressure and esophageal motility, in addition to phases of dissociation between the LES and the diaphragm, which is when most GERD episodes occur.

In such contexts, “it would appear that sports-related exercise has a relatively detrimental effect on the gastroesophageal junction and anti-GERD mechanisms,” said Dr. Zerbib. Meta-analyses provide answers to some questions, but not all; the situation is much less clear when it comes to non–sports-related exercise.”
 

Not so simple

“Taking into account only patients whose GERD has been confirmed through esophageal pH monitoring, exercise does not appear to significantly impact GERD symptoms or the characteristics seen on pH monitoring,” said Dr. Zerbib.

These results come from a study of 100 patients whose exercise level was assessed using the International Physical Activity Questionnaire and expressed using the standard metric of metabolic rate by minutes of performance during a week (METs-minute/week).

This questionnaire is used for most studies that assess exercise and separates patients into three groups (low, moderate, or high) based on their level of exercise. In essence, it considers the duration of exercise but not the type (that is, professional, recreational, and so on) or intensity, resulting in a key methodological issue to consider during the analysis, for example, of the results of a large meta-analysis on the topic.

The meta-analysis in question included 78,000 patients, of whom 10,000 had GERD symptoms.

Based on the results, exercise decreases the risk of GERD by about one-third, after adjustment for body mass index (BMI). “This last point is important,” Dr. Zerbib noted, “since adjusting for BMI without providing the nonadjusted data fails to identify whether exercise decreases the risk of GERD because of the effect on the BMI.* What’s more, when it comes to complications of GERD, like Barrett’s esophagus or adenocarcinoma, the data are far fewer and less robust, with negative case-control studies for the most part.”

One of these two studies, which concerned non–sports-related exercise and the onset of Barrett’s esophagus, reported no association (odds ratio, 1.19; 95% confidence interval, 0.82-1.73).

“Exercise considered vigorous (sports-related) contributes to GERD by altering the antireflux barrier (LES/diaphragm dissociation) and increasing constraints on the esophageal junction (abdominal pressure). In the general population, regular exercise likely decreases the risk of pathological GERD. When it comes to complications of GERD, the data are not very robust, mostly because the studies omitted several exercise-related (healthy lifestyle) factors,” said Dr. Zerbib.
 

Several confounding factors

It’s difficult to issue an opinion under these conditions. There are several confounding factors that studies rarely address. Although the studies always included factors such as age, sex, or BMI, other parameters related to a healthy lifestyle, whether directly or indirectly connected to exercise, were never mentioned. Indeed, diet (such as high calorie or high fat) is known to lead to an increased incidence of GERD. The same goes for alcohol use. Occupation also likely plays a role, but the studies do not mention this.

“So, it’s easy to imagine that a patient who regularly exercises likely eats healthier than a sedentary patient, which comes with the likelihood of a lower risk of developing GERD symptoms,” said Dr. Zerbib. “Overall, evaluating the impact of exercise on GERD is no small feat. It can be said with relative certainty that exercise contributes to GERD through a proven pathophysiology. In the general population, however, exercise likely reduces the risk of GERD but not of its complications. Other than the impact on weight and abdominal obesity, the reality is that a lack of exercise is associated with a less healthy lifestyle and, therefore, behaviors that contribute to GERD.”

Dr. Zerbib reported no conflicts of interest connected to this presentation.

* From a pathophysiological standpoint, the evidence is clear that a high BMI increases the gastroesophageal pressure gradient and dissociation between the LES and the diaphragm, whether temporarily or permanently, as in the case of a hiatal hernia. Abdominal obesity increases constraints on the gastroesophageal junction and results in a two- to threefold increase in the risk of GERD and its complications.

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

A previously healthy 37-year-old runner presented to his primary care physician with acute-onset floaters and scotoma in his left eye, which he first noticed less than 24 hours earlier. He denied eye pain, diplopia, headache, fever, chills, slurred speech, weakness, or other focal neurologic deficits. His vital signs were normal.

Despite the acute visual disturbances, visual acuity was 20/20 in both eyes with corrective lenses; pupils were equal, round, and reactive to light and accommodation; and extraocular movements were intact. On a dilated funduscopic exam, the physician discovered edema of the optic cup, tortuous vasculature, and microhemorrhages in the left eye (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient was given a diagnosis of central retinal vein occlusion (CRVO). In this condition, a blockage causes the central retinal vein to leak blood and excess fluid into the retina. This fluid can collect in the macula, leading to visual disturbance.

Cases of central retinal vein occlusion have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise.

Retinal vein occlusion is the second most common retinal vascular disease in the United States and is one of the most common causes of vision loss in the elderly.¹ Advancing age (≥ 70 years), increasing mean arterial blood pressure, and retinal atherosclerotic signs (focal narrowing, arteriovenous nicking, and opacification) are significant predictors of retinal vein occlusion.² Other risk factors include diabetes, hyperlipidemia, cardiovascular disease, smoking, obesity, hypercoagulable state, and glaucoma.^3-7 However, retinal vein occlusion may also occur in younger, healthier patients who lack the aforementioned risk factors. In such cases, thrombophilic risk factors should be considered.⁸

CRVO is classified as either ischemic or nonischemic (perfused) based on retinal angiography. More than 80% of CRVO cases are nonischemic,⁹ of which the majority has visual acuity better than 20/400, mild or no pupillary defect, and mild, unilateral visual changes.¹⁰ Nonischemic CRVO can progress to ischemic CRVO, which can result in permanent vision loss. Visual outcome is good in nonischemic CRVO and poor in ischemic CRVO.¹¹ Early detection of poor prognostic features, such as macular edema and neovascularization, is essential for minimizing the risk for permanent damage.¹²

Dilated funduscopic exam of a patient with CRVO may reveal widespread retinal hemorrhages, markedly dilated and tortuous retinal vessels, cotton wool spots, optic disc or macular edema, and/or vitreous hemorrhages.¹⁰

Differential includes varied conditions that can affect vision

CRVO may manifest similarly to the following:

Proliferative diabetic retinopathy can manifest with retinal edema or vitreous and retinal hemorrhages, which also are seen in CRVO.¹³ Macular edema, retinal hemorrhage, and neovascularization on the optic disc or retinal surface also may be seen on funduscopy in proliferative diabetic retinopathy.¹⁴ However, proliferative diabetic retinopathy is often bilateral and gradual in onset in patients with longstanding, uncontrolled diabetes.

Continue to: Hyperviscosity retinopathy

Hyperviscosity retinopathy, which is commonly caused by plasma cell and erythrocyte disorders, also manifests similarly to CRVO. Two noticeable differences include its bilateral presentation and Roth spots, neither of which are commonly seen in CRVO. In addition to visual abnormalities, mucosal bleeding and neurologic abnormalities complete the classic triad of hyperviscosity.¹⁵

Ocular ischemic syndrome is often confused with diabetic retinopathies and CRVO on funduscopy. However, patients with this condition may have narrowed retinal arteries, perifoveal telangiectasias, and periorbital pain—findings rarely seen in CRVO.¹⁶ Because ocular ischemic syndrome is a manifestation of severe carotid artery atherosclerosis, constitutional symptoms also may be present.

The work-up

When CRVO is suspected, an extensive laboratory work-up is necessary to determine the underlying etiology, including: blood pressure, electrocardiogram, complete blood count, random glucose level, electrolytes, lipid panel, plasma protein electrophoresis, thyroid function tests, and inflammatory markers.¹

Additional testing may be required for younger patients who lack vasculopathic risk factors, who have bilateral CRVO, or who have a personal or family history of thrombosis.¹ These patients should be screened for thrombophilia, hypercoagulable disorders, and homocysteinuria.¹

Cases of CRVO have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise, excessive vomiting, or extended periods of fasting.^17-19

Continue to: Treatment may include injections, surgery, or nothing at all

Currently, there are no proven treatments to reopen occluded retinal veins. Thus, management is directed at complications that contribute to vision loss, including macular edema and neovascularization.^20-21 Intravitreal anti-vascular endothelial growth factor (VEGF) agents are recognized as first-line therapy for macular edema in numerous studies.^22-26 Intravitreal corticosteroids are an alternative treatment for patients with macular edema who do not respond to anti-VEGF therapy; however, monitoring is required as these corticosteroids increase the risk for glaucoma and cataract formation.²⁷ In patients with CRVO with neovascularization, panretinal laser photocoagulation may be used.²⁸

Observation and monitoring for the development of complications, rather than initiation of treatment, is appropriate for patients with CRVO without macular edema or neovascularization, with follow-up intervals and duration dictated by the severity of visual loss and whether the CRVO was ischemic or nonischemic.

Our patient’s diagnosis was confirmed by retinal specialists with optic coherence tomography, gonioscopy, and fluorescein angiography. He underwent an extensive laboratory work-up and hypercoagulation studies to determine the etiology. All results returned within normal limits with the exception of a nonspecific pattern found on serum protein electrophoresis that suggested dehydration.

Observation and monitoring for the development of complications is appropriate for patients with central retinal vein occlusion without macular edema.

Given his negative hypercoagulation studies, normal laboratory values, and new exercise regimen, dehydration was concluded to be the likely etiology. Since his visual acuity was not affected, observation with bimonthly follow-up for 6 months was the management strategy. He was also encouraged to maintain adequate hydration during exercise. His vision returned to normal 2 weeks after the initial event, and he did not have recurrence during the monitoring period.

A previously healthy 37-year-old runner presented to his primary care physician with acute-onset floaters and scotoma in his left eye, which he first noticed less than 24 hours earlier. He denied eye pain, diplopia, headache, fever, chills, slurred speech, weakness, or other focal neurologic deficits. His vital signs were normal.

Despite the acute visual disturbances, visual acuity was 20/20 in both eyes with corrective lenses; pupils were equal, round, and reactive to light and accommodation; and extraocular movements were intact. On a dilated funduscopic exam, the physician discovered edema of the optic cup, tortuous vasculature, and microhemorrhages in the left eye (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient was given a diagnosis of central retinal vein occlusion (CRVO). In this condition, a blockage causes the central retinal vein to leak blood and excess fluid into the retina. This fluid can collect in the macula, leading to visual disturbance.

Cases of central retinal vein occlusion have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise.

Retinal vein occlusion is the second most common retinal vascular disease in the United States and is one of the most common causes of vision loss in the elderly.¹ Advancing age (≥ 70 years), increasing mean arterial blood pressure, and retinal atherosclerotic signs (focal narrowing, arteriovenous nicking, and opacification) are significant predictors of retinal vein occlusion.² Other risk factors include diabetes, hyperlipidemia, cardiovascular disease, smoking, obesity, hypercoagulable state, and glaucoma.^3-7 However, retinal vein occlusion may also occur in younger, healthier patients who lack the aforementioned risk factors. In such cases, thrombophilic risk factors should be considered.⁸

CRVO is classified as either ischemic or nonischemic (perfused) based on retinal angiography. More than 80% of CRVO cases are nonischemic,⁹ of which the majority has visual acuity better than 20/400, mild or no pupillary defect, and mild, unilateral visual changes.¹⁰ Nonischemic CRVO can progress to ischemic CRVO, which can result in permanent vision loss. Visual outcome is good in nonischemic CRVO and poor in ischemic CRVO.¹¹ Early detection of poor prognostic features, such as macular edema and neovascularization, is essential for minimizing the risk for permanent damage.¹²

Dilated funduscopic exam of a patient with CRVO may reveal widespread retinal hemorrhages, markedly dilated and tortuous retinal vessels, cotton wool spots, optic disc or macular edema, and/or vitreous hemorrhages.¹⁰

Differential includes varied conditions that can affect vision

CRVO may manifest similarly to the following:

Proliferative diabetic retinopathy can manifest with retinal edema or vitreous and retinal hemorrhages, which also are seen in CRVO.¹³ Macular edema, retinal hemorrhage, and neovascularization on the optic disc or retinal surface also may be seen on funduscopy in proliferative diabetic retinopathy.¹⁴ However, proliferative diabetic retinopathy is often bilateral and gradual in onset in patients with longstanding, uncontrolled diabetes.

Continue to: Hyperviscosity retinopathy

Hyperviscosity retinopathy, which is commonly caused by plasma cell and erythrocyte disorders, also manifests similarly to CRVO. Two noticeable differences include its bilateral presentation and Roth spots, neither of which are commonly seen in CRVO. In addition to visual abnormalities, mucosal bleeding and neurologic abnormalities complete the classic triad of hyperviscosity.¹⁵

Ocular ischemic syndrome is often confused with diabetic retinopathies and CRVO on funduscopy. However, patients with this condition may have narrowed retinal arteries, perifoveal telangiectasias, and periorbital pain—findings rarely seen in CRVO.¹⁶ Because ocular ischemic syndrome is a manifestation of severe carotid artery atherosclerosis, constitutional symptoms also may be present.

The work-up

When CRVO is suspected, an extensive laboratory work-up is necessary to determine the underlying etiology, including: blood pressure, electrocardiogram, complete blood count, random glucose level, electrolytes, lipid panel, plasma protein electrophoresis, thyroid function tests, and inflammatory markers.¹

Additional testing may be required for younger patients who lack vasculopathic risk factors, who have bilateral CRVO, or who have a personal or family history of thrombosis.¹ These patients should be screened for thrombophilia, hypercoagulable disorders, and homocysteinuria.¹

Cases of CRVO have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise, excessive vomiting, or extended periods of fasting.^17-19

Continue to: Treatment may include injections, surgery, or nothing at all

Currently, there are no proven treatments to reopen occluded retinal veins. Thus, management is directed at complications that contribute to vision loss, including macular edema and neovascularization.^20-21 Intravitreal anti-vascular endothelial growth factor (VEGF) agents are recognized as first-line therapy for macular edema in numerous studies.^22-26 Intravitreal corticosteroids are an alternative treatment for patients with macular edema who do not respond to anti-VEGF therapy; however, monitoring is required as these corticosteroids increase the risk for glaucoma and cataract formation.²⁷ In patients with CRVO with neovascularization, panretinal laser photocoagulation may be used.²⁸

Observation and monitoring for the development of complications, rather than initiation of treatment, is appropriate for patients with CRVO without macular edema or neovascularization, with follow-up intervals and duration dictated by the severity of visual loss and whether the CRVO was ischemic or nonischemic.

Our patient’s diagnosis was confirmed by retinal specialists with optic coherence tomography, gonioscopy, and fluorescein angiography. He underwent an extensive laboratory work-up and hypercoagulation studies to determine the etiology. All results returned within normal limits with the exception of a nonspecific pattern found on serum protein electrophoresis that suggested dehydration.

Observation and monitoring for the development of complications is appropriate for patients with central retinal vein occlusion without macular edema.

Given his negative hypercoagulation studies, normal laboratory values, and new exercise regimen, dehydration was concluded to be the likely etiology. Since his visual acuity was not affected, observation with bimonthly follow-up for 6 months was the management strategy. He was also encouraged to maintain adequate hydration during exercise. His vision returned to normal 2 weeks after the initial event, and he did not have recurrence during the monitoring period.

A previously healthy 37-year-old runner presented to his primary care physician with acute-onset floaters and scotoma in his left eye, which he first noticed less than 24 hours earlier. He denied eye pain, diplopia, headache, fever, chills, slurred speech, weakness, or other focal neurologic deficits. His vital signs were normal.

Despite the acute visual disturbances, visual acuity was 20/20 in both eyes with corrective lenses; pupils were equal, round, and reactive to light and accommodation; and extraocular movements were intact. On a dilated funduscopic exam, the physician discovered edema of the optic cup, tortuous vasculature, and microhemorrhages in the left eye (FIGURE).

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

The patient was given a diagnosis of central retinal vein occlusion (CRVO). In this condition, a blockage causes the central retinal vein to leak blood and excess fluid into the retina. This fluid can collect in the macula, leading to visual disturbance.

Cases of central retinal vein occlusion have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise.

Retinal vein occlusion is the second most common retinal vascular disease in the United States and is one of the most common causes of vision loss in the elderly.¹ Advancing age (≥ 70 years), increasing mean arterial blood pressure, and retinal atherosclerotic signs (focal narrowing, arteriovenous nicking, and opacification) are significant predictors of retinal vein occlusion.² Other risk factors include diabetes, hyperlipidemia, cardiovascular disease, smoking, obesity, hypercoagulable state, and glaucoma.^3-7 However, retinal vein occlusion may also occur in younger, healthier patients who lack the aforementioned risk factors. In such cases, thrombophilic risk factors should be considered.⁸

CRVO is classified as either ischemic or nonischemic (perfused) based on retinal angiography. More than 80% of CRVO cases are nonischemic,⁹ of which the majority has visual acuity better than 20/400, mild or no pupillary defect, and mild, unilateral visual changes.¹⁰ Nonischemic CRVO can progress to ischemic CRVO, which can result in permanent vision loss. Visual outcome is good in nonischemic CRVO and poor in ischemic CRVO.¹¹ Early detection of poor prognostic features, such as macular edema and neovascularization, is essential for minimizing the risk for permanent damage.¹²

Dilated funduscopic exam of a patient with CRVO may reveal widespread retinal hemorrhages, markedly dilated and tortuous retinal vessels, cotton wool spots, optic disc or macular edema, and/or vitreous hemorrhages.¹⁰

Differential includes varied conditions that can affect vision

CRVO may manifest similarly to the following:

Proliferative diabetic retinopathy can manifest with retinal edema or vitreous and retinal hemorrhages, which also are seen in CRVO.¹³ Macular edema, retinal hemorrhage, and neovascularization on the optic disc or retinal surface also may be seen on funduscopy in proliferative diabetic retinopathy.¹⁴ However, proliferative diabetic retinopathy is often bilateral and gradual in onset in patients with longstanding, uncontrolled diabetes.

Continue to: Hyperviscosity retinopathy

Hyperviscosity retinopathy, which is commonly caused by plasma cell and erythrocyte disorders, also manifests similarly to CRVO. Two noticeable differences include its bilateral presentation and Roth spots, neither of which are commonly seen in CRVO. In addition to visual abnormalities, mucosal bleeding and neurologic abnormalities complete the classic triad of hyperviscosity.¹⁵

Ocular ischemic syndrome is often confused with diabetic retinopathies and CRVO on funduscopy. However, patients with this condition may have narrowed retinal arteries, perifoveal telangiectasias, and periorbital pain—findings rarely seen in CRVO.¹⁶ Because ocular ischemic syndrome is a manifestation of severe carotid artery atherosclerosis, constitutional symptoms also may be present.

The work-up

When CRVO is suspected, an extensive laboratory work-up is necessary to determine the underlying etiology, including: blood pressure, electrocardiogram, complete blood count, random glucose level, electrolytes, lipid panel, plasma protein electrophoresis, thyroid function tests, and inflammatory markers.¹

Additional testing may be required for younger patients who lack vasculopathic risk factors, who have bilateral CRVO, or who have a personal or family history of thrombosis.¹ These patients should be screened for thrombophilia, hypercoagulable disorders, and homocysteinuria.¹

Cases of CRVO have been linked to dehydration as well, with acute vision changes occurring after strenuous exercise, excessive vomiting, or extended periods of fasting.^17-19

Continue to: Treatment may include injections, surgery, or nothing at all

Currently, there are no proven treatments to reopen occluded retinal veins. Thus, management is directed at complications that contribute to vision loss, including macular edema and neovascularization.^20-21 Intravitreal anti-vascular endothelial growth factor (VEGF) agents are recognized as first-line therapy for macular edema in numerous studies.^22-26 Intravitreal corticosteroids are an alternative treatment for patients with macular edema who do not respond to anti-VEGF therapy; however, monitoring is required as these corticosteroids increase the risk for glaucoma and cataract formation.²⁷ In patients with CRVO with neovascularization, panretinal laser photocoagulation may be used.²⁸

Observation and monitoring for the development of complications, rather than initiation of treatment, is appropriate for patients with CRVO without macular edema or neovascularization, with follow-up intervals and duration dictated by the severity of visual loss and whether the CRVO was ischemic or nonischemic.

Our patient’s diagnosis was confirmed by retinal specialists with optic coherence tomography, gonioscopy, and fluorescein angiography. He underwent an extensive laboratory work-up and hypercoagulation studies to determine the etiology. All results returned within normal limits with the exception of a nonspecific pattern found on serum protein electrophoresis that suggested dehydration.

Observation and monitoring for the development of complications is appropriate for patients with central retinal vein occlusion without macular edema.

Given his negative hypercoagulation studies, normal laboratory values, and new exercise regimen, dehydration was concluded to be the likely etiology. Since his visual acuity was not affected, observation with bimonthly follow-up for 6 months was the management strategy. He was also encouraged to maintain adequate hydration during exercise. His vision returned to normal 2 weeks after the initial event, and he did not have recurrence during the monitoring period.

I’ve always thought it was interesting that the first cases of COVID-19 were reported to the World Health Organization on December 31, 2019.¹ How close we came to having COVID-20! On January 31, 2020, the US Department of Health and Human Services declared a national public health emergency due to COVID-19, and it’s been in effect ever since.

As COVID and our knowledge about it changed, we rewrote policies dozens of times, and each time the staff retrained in a hurry.

A national public health emergency allows the Department of Health and Human Services to access and designate funds to diagnose, treat, and prevent disease in response to the emergency. The declaration also facilitates the Centers for Disease Control and Prevention response to an infectious disease emergency. There are provisions for modifications to Medicare, Medicaid, and the Children’s Health Insurance Program so clinicians can continue seeing patients and be reimbursed for doing so, even in a situation in which the emergency disrupts usual reporting and documentation requirements. The declaration is essentially a shortcut through the typical bureaucracy that too often gums up the practice of medicine²; it allows for the rapid deployment of funds and personnel to a community affected by an emergency.

Unprecedented change. In the early days, plastic partitions were erected between patients in the hospital, and the scarce supply of N-95 masks was stored in paper bags and baked at low temperatures in ovens overnight.

My hospital enacted its incident command response procedures, just as we did the day our community experienced a mass shooting—except incident command stayed open for months. We had to adapt quickly. My office never closed to in-­person visits; we decided that we took care of too many people who did not have other access to care to make closing practical. My practice partners and I spent a Friday afternoon in March 2020 writing policies. A policy for our residency practice. A policy for how to see patients who might have COVID. A policy for how to cover the residents and faculty when we inevitably got sick. A policy for how to do telehealth visits. By the following Monday, when the office reopened, we had already trained the staff on the new policies, and we were ready to implement them with our patients.

As COVID and our knowledge about it changed, we rewrote those policies dozens of times, and each time the staff retrained in a hurry. We all learned so much so quickly. So as the official public health emergency comes to an end, there are things that I think I will take from it, and things that I wish all of medicine could take from it too.

We adapted as a team. I will never forget the stress of the early days of the emergency, when the patient volume was overwhelming and the death rate was staggering. But shining through those dark times were wonderful moments of connection with the teams with which I worked. I think about the residents whose training shifted suddenly to full-time ­COVID, the nurses who learned new things every weekend for so many months, and everyone who went out on a limb to do the right thing.

We provided care without bureaucracy. I wish medicine could leave the bureaucracy behind along with the emergency. It was so much easier to practice medicine when we knew that the testing and treatment were covered, without “we’ll see” or “it depends on your insurance.” Telehealth is probably here to stay, thanks to widespread uptake by patients and clinicians alike during the pandemic. My wish is that we can make it as easy as possible to use going forward, instead of choosing to return to a more restricted and difficult path.^3,4

Family physicians have much to be proud of. We can look back on the COVID-19 public health emergency as a time when we absorbed a huge amount of rapidly changing information and showed our adaptability to a frightening and uncertain environment. We are not returning to the office, as so many Americans are these days, because we never left the many settings where family physicians practice. We remained at work during the emergency and we took care of our patients.

When the next emergency is declared—whether it be national or local—we will once again be there for our patients.

I’ve always thought it was interesting that the first cases of COVID-19 were reported to the World Health Organization on December 31, 2019.¹ How close we came to having COVID-20! On January 31, 2020, the US Department of Health and Human Services declared a national public health emergency due to COVID-19, and it’s been in effect ever since.

As COVID and our knowledge about it changed, we rewrote policies dozens of times, and each time the staff retrained in a hurry.

A national public health emergency allows the Department of Health and Human Services to access and designate funds to diagnose, treat, and prevent disease in response to the emergency. The declaration also facilitates the Centers for Disease Control and Prevention response to an infectious disease emergency. There are provisions for modifications to Medicare, Medicaid, and the Children’s Health Insurance Program so clinicians can continue seeing patients and be reimbursed for doing so, even in a situation in which the emergency disrupts usual reporting and documentation requirements. The declaration is essentially a shortcut through the typical bureaucracy that too often gums up the practice of medicine²; it allows for the rapid deployment of funds and personnel to a community affected by an emergency.

Unprecedented change. In the early days, plastic partitions were erected between patients in the hospital, and the scarce supply of N-95 masks was stored in paper bags and baked at low temperatures in ovens overnight.

My hospital enacted its incident command response procedures, just as we did the day our community experienced a mass shooting—except incident command stayed open for months. We had to adapt quickly. My office never closed to in-­person visits; we decided that we took care of too many people who did not have other access to care to make closing practical. My practice partners and I spent a Friday afternoon in March 2020 writing policies. A policy for our residency practice. A policy for how to see patients who might have COVID. A policy for how to cover the residents and faculty when we inevitably got sick. A policy for how to do telehealth visits. By the following Monday, when the office reopened, we had already trained the staff on the new policies, and we were ready to implement them with our patients.

As COVID and our knowledge about it changed, we rewrote those policies dozens of times, and each time the staff retrained in a hurry. We all learned so much so quickly. So as the official public health emergency comes to an end, there are things that I think I will take from it, and things that I wish all of medicine could take from it too.

We adapted as a team. I will never forget the stress of the early days of the emergency, when the patient volume was overwhelming and the death rate was staggering. But shining through those dark times were wonderful moments of connection with the teams with which I worked. I think about the residents whose training shifted suddenly to full-time ­COVID, the nurses who learned new things every weekend for so many months, and everyone who went out on a limb to do the right thing.

We provided care without bureaucracy. I wish medicine could leave the bureaucracy behind along with the emergency. It was so much easier to practice medicine when we knew that the testing and treatment were covered, without “we’ll see” or “it depends on your insurance.” Telehealth is probably here to stay, thanks to widespread uptake by patients and clinicians alike during the pandemic. My wish is that we can make it as easy as possible to use going forward, instead of choosing to return to a more restricted and difficult path.^3,4

Family physicians have much to be proud of. We can look back on the COVID-19 public health emergency as a time when we absorbed a huge amount of rapidly changing information and showed our adaptability to a frightening and uncertain environment. We are not returning to the office, as so many Americans are these days, because we never left the many settings where family physicians practice. We remained at work during the emergency and we took care of our patients.

When the next emergency is declared—whether it be national or local—we will once again be there for our patients.

I’ve always thought it was interesting that the first cases of COVID-19 were reported to the World Health Organization on December 31, 2019.¹ How close we came to having COVID-20! On January 31, 2020, the US Department of Health and Human Services declared a national public health emergency due to COVID-19, and it’s been in effect ever since.

As COVID and our knowledge about it changed, we rewrote policies dozens of times, and each time the staff retrained in a hurry.

A national public health emergency allows the Department of Health and Human Services to access and designate funds to diagnose, treat, and prevent disease in response to the emergency. The declaration also facilitates the Centers for Disease Control and Prevention response to an infectious disease emergency. There are provisions for modifications to Medicare, Medicaid, and the Children’s Health Insurance Program so clinicians can continue seeing patients and be reimbursed for doing so, even in a situation in which the emergency disrupts usual reporting and documentation requirements. The declaration is essentially a shortcut through the typical bureaucracy that too often gums up the practice of medicine²; it allows for the rapid deployment of funds and personnel to a community affected by an emergency.

Unprecedented change. In the early days, plastic partitions were erected between patients in the hospital, and the scarce supply of N-95 masks was stored in paper bags and baked at low temperatures in ovens overnight.

My hospital enacted its incident command response procedures, just as we did the day our community experienced a mass shooting—except incident command stayed open for months. We had to adapt quickly. My office never closed to in-­person visits; we decided that we took care of too many people who did not have other access to care to make closing practical. My practice partners and I spent a Friday afternoon in March 2020 writing policies. A policy for our residency practice. A policy for how to see patients who might have COVID. A policy for how to cover the residents and faculty when we inevitably got sick. A policy for how to do telehealth visits. By the following Monday, when the office reopened, we had already trained the staff on the new policies, and we were ready to implement them with our patients.

As COVID and our knowledge about it changed, we rewrote those policies dozens of times, and each time the staff retrained in a hurry. We all learned so much so quickly. So as the official public health emergency comes to an end, there are things that I think I will take from it, and things that I wish all of medicine could take from it too.

We adapted as a team. I will never forget the stress of the early days of the emergency, when the patient volume was overwhelming and the death rate was staggering. But shining through those dark times were wonderful moments of connection with the teams with which I worked. I think about the residents whose training shifted suddenly to full-time ­COVID, the nurses who learned new things every weekend for so many months, and everyone who went out on a limb to do the right thing.

We provided care without bureaucracy. I wish medicine could leave the bureaucracy behind along with the emergency. It was so much easier to practice medicine when we knew that the testing and treatment were covered, without “we’ll see” or “it depends on your insurance.” Telehealth is probably here to stay, thanks to widespread uptake by patients and clinicians alike during the pandemic. My wish is that we can make it as easy as possible to use going forward, instead of choosing to return to a more restricted and difficult path.^3,4

Family physicians have much to be proud of. We can look back on the COVID-19 public health emergency as a time when we absorbed a huge amount of rapidly changing information and showed our adaptability to a frightening and uncertain environment. We are not returning to the office, as so many Americans are these days, because we never left the many settings where family physicians practice. We remained at work during the emergency and we took care of our patients.

When the next emergency is declared—whether it be national or local—we will once again be there for our patients.

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ­ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

Copyright KO Studios

Much of the persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVDby ascertaining LDL-C

The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL), estimation of LDL-C is invalid.

The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very-low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC – HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴

National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵

Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ­ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

Continue to: Apolipoprotein B

Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the ­LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴

Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

Continue to: How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention:Stratification by age

40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force ­(USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

Continue to: In adults at borderline risk...

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify ­moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴

Continue to: > 75 years, without ASCVD

> 75 years, without ASCVD. In this group, the ­benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

A meta-analysis of 28 trials demonstrated that people > 75 years of age had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C.

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ­ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

Base a recommendation for preventive intervention, such as lipidlowering therapy, on the estimated 10-year risk for ASCVD.

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/­kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy

Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

Ezetimibe, a selective cholesterol-­absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴

PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23

Continue to: Inclisiran

Inclisiran, an injectable small-­interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴

Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28

Bempedoic acid is a small-molecule ­inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-­intolerant patients, bempedoic acid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰

Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL) and TG (42 mg/dL).^31,32

Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; ­HDL-C < 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

At-risk patients should follow a dietary pattern that emphasizes vegetables, fruits, and whole grains and limits sweets, sugarsweetened beverages, and red meat.

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴

CORRESPONDENCE
Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; [email protected]

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ­ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

Copyright KO Studios

Much of the persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVDby ascertaining LDL-C

The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL), estimation of LDL-C is invalid.

The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very-low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC – HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴

National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵

Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ­ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

Continue to: Apolipoprotein B

Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the ­LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴

Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

Continue to: How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention:Stratification by age

40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force ­(USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

Continue to: In adults at borderline risk...

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify ­moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴

Continue to: > 75 years, without ASCVD

> 75 years, without ASCVD. In this group, the ­benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

A meta-analysis of 28 trials demonstrated that people > 75 years of age had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C.

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ­ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

Base a recommendation for preventive intervention, such as lipidlowering therapy, on the estimated 10-year risk for ASCVD.

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/­kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy

Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

Ezetimibe, a selective cholesterol-­absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴

PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23

Continue to: Inclisiran

Inclisiran, an injectable small-­interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴

Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28

Bempedoic acid is a small-molecule ­inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-­intolerant patients, bempedoic acid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰

Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL) and TG (42 mg/dL).^31,32

Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; ­HDL-C < 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

At-risk patients should follow a dietary pattern that emphasizes vegetables, fruits, and whole grains and limits sweets, sugarsweetened beverages, and red meat.

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴

CORRESPONDENCE
Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; [email protected]

An elevated serum level of cholesterol has been recognized as a risk factor for atherosclerotic cardiovascular disease (ASCVD) since the publication of the Framingham Study in 1961.¹ Although clinical outcomes related to ASCVD have improved in recent decades, ASCVD remains the leading cause of morbidity and mortality across the globe and remains, in the United States, the leading cause of death among most racial and ethnic groups. Much of this persistent disease burden can be attributed to inadequate control of ­ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.²

Copyright KO Studios

Much of the persistent disease burden can be attributed to inadequate control of ASCVD risk factors and suboptimal implementation of prevention strategies in the general population.

The most recent (2019) iteration of the American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease emphasizes a comprehensive, patient-centered, team-based approach to the management of ASCVD risk factors.² In this article, I review how, first, medication to reduce ASCVD risk should be considered only when a patient’s risk is sufficiently high and, second, shared decision-making and social determinants of health should, in all cases, guide and inform optimal implementation of treatment.²

Estimating risk for ASCVDby ascertaining LDL-C

The Friedewald equation. Traditionally, low-density lipoprotein cholesterol (LDL-C) is estimated using the Friedewald equation^a applied to a fasting lipid profile. In patients who have a low level of LDL-C (< 70 mg/dL), however, the Friedewald equation becomes less accurate; in patients with hypertriglyceridemia (TG ≥ 400 mg/dL), estimation of LDL-C is invalid.

The Martin–Hopkins equation offers a validated estimation of LDL-C when the LDL-C value is < 70 mg/dL.³ This equation—in which the fixed factor of 5 used in the Friedewald equation to estimate very-low-density lipoprotein cholesterol is replaced by an adjustable factor that is based on the patient’s non-HDL-C (ie, TC – HDL-C) and TG values—is preferred by the ACC/AHA Task Force on Clinical Practice Guidelines in this clinical circumstance.⁴

National Institutes of Health equation. This newer equation provides an accurate estimate of the LDL-C level in patients whose TG value is ≤ 800 mg/dL. The equation has not been fully validated for clinical use, however.⁵

Direct measurement obviates the need for an equation to estimate LDL-C, but the test is not available in all health care settings.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ­ASCVD risk and document the baseline LDL-C level. If the TG level is ≥ 400 mg/dL, the test should be administered in the fasting state.⁴

Continue to: Apolipoprotein B

Apolipoprotein B. Alternatively, apolipoprotein B (apoB) can be measured. Because each LDL-C particle contains 1 apoB molecule, the apoB level describes the ­LDL-C level more accurately than a calculation of LDL-C. Many patients with type 2 diabetes and metabolic syndrome have a relatively low calculated LDL-C (thereby falsely reassuring the testing clinician) but have an elevated apoB level. An apoB level ≥ 130 mg/dL corresponds to an LDL-C level >160 mg/dL.⁴

Calculation of non-HDL-C. Because the nonfasting state does not have a significant impact on a patient’s TC and HDL-C levels, the non-HDL-C level also can be calculated from the results of a nonfasting lipid profile.

Non-HDL-C and apoB are equivalent predictors of ASCVD risk. These 2 assessments might offer better risk estimation than other available tools in patients who have type 2 diabetes and metabolic syndrome.⁶

Applying the estimate of 10-year ASCVD risk

Your recommendation for preventive intervention, such as lipid-lowering therapy, should be based on the estimated 10-year risk for ASCVD. Although multiple validated risk assessment tools are available, ACC/AHA recommends the pooled cohort risk equations (PCE), introduced in the 2013 ACC/AHA cholesterol treatment guidelines. The Framingham Heart Study now recommends the ACC/AHA PCE for risk assessment as well.⁷

The PCE, developed from 5 large cohorts, is based on hard atherosclerotic events: nonfatal myocardial infarction, death from coronary artery disease, and stroke. The ACC/AHA PCE is the only risk assessment tool developed using a significant percentage of patients who self-identify as Black.⁸ Alternatives to the ACC/AHA PCE include:

• Multi-ethnic Study of Atherosclerosis (MESA) 10-year ASCVD risk calculator, which incorporates the coronary artery calcium (CAC) score.
• Reynolds Risk Score, which incorporates high-sensitivity C-reactive protein measurement and a family history of premature ASCVD.⁹

Continue to: How much does lifestyle modification actually matter?

The absolute impact of diet and exercise on lipid parameters is relatively modest. No studies have demonstrated a reduction in adverse cardiovascular outcomes with specific interventions regarding diet or activity.

Diet. Nevertheless, ACC/AHA recommends that at-risk patients follow a dietary pattern that (1) emphasizes vegetables, fruits, and whole grains and (2) limits sweets, sugar-sweetened beverages, and red meat.

For adults ≥ 20 years of age who are not receiving lipid-lowering therapy, a nonfasting lipid profile can be used to estimate ASCVD risk and document the baseline LDL-C level.

Saturated fat should constitute no more than 5% or 6% of total calories. In controlled-feeding trials,¹⁰ for every 1% of calories from saturated fat that are replaced with carbohydrate or monounsaturated or polyunsaturated fat, the LDL-C level was found to decline by as much as 1.8 mg/dL. Evidence is insufficient to assert that lowering dietary cholesterol reduces LDL-C.¹¹

Activity. Trials of aerobic physical activity, compared with a more sedentary activity pattern, have demonstrated a reduction in the LDL-C level of as much as 6 mg/dL. All adult patients should be counseled to engage in aerobic physical activity of moderate or vigorous intensity—averaging ≥ 40 minutes per session, 3 or 4 sessions per week.¹¹

Primary prevention:Stratification by age

40 to 75 years. ACC/AHA recommends that you routinely assess traditional cardiovascular risk factors for these patients and calculate their 10-year risk for ASCVD using the PCE. Statin therapy as primary prevention is indicated for 3 major groups (TABLE 1).⁴ The US Preventive Services Task Force ­(USPSTF) recommends a 10-year ASCVD risk ≥ 10%, in conjunction with 1 or more additional CVD risk factors (dyslipidemia, diabetes, hypertension, smoking), as the threshold for initiating low- or moderate-intensity statin therapy in this age group.¹²

Continue to: In adults at borderline risk...

In adults at borderline risk (5% to < 7.5% 10-year ASCVD risk) or intermediate risk (≥ 7.5% to < 20% 10-year ASCVD risk), consider risk-enhancing factors to better inform your recommendation for preventive interventions. In these 2 groups, the presence of risk-enhancing factors might justify ­moderate-intensity statin therapy (TABLE 2⁴).

If your decision regarding preventive intervention remains uncertain, measuring CAC might further guide your discussion with the patient.⁴ When the CAC score is:

• 0 Agatston units and higher-risk conditions (eg, diabetes, family history of premature coronary artery disease, smoking) are absent, statin therapy can be withheld; reassess ASCVD risk in 5 to 10 years.
• 1-99 Agatston units, statin therapy can be started, especially for patients ≥ 55 years of age.
• ≥ 100 Agatston units or ≥ 75th percentile, statin therapy is indicated for all patients, regardless of additional risk factors.⁴

Because statins promote progression from unstable, inflammatory atherosclerotic plaque to more stable, calcified plaque, CAC scoring is not valid in patients already on statin therapy.¹³

In primary prevention, patients who have been classified as having low or intermediate risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have an annual all-cause mortality < 1%, regardless of age and gender. Patients classified as being at high risk, based on ASCVD risk scoring, with a CAC score of 0 Agatston units, have a significantly lower annual mortality than low- or intermediate-risk patients with a CAC score > 0 Agatston units.¹⁴

20 to 39 years. Focus on evaluation of lifetime ASCVD risk, rather than short-term (10-year) risk. Lifestyle modification is the primary intervention for younger patients; for those with moderate hypercholesterolemia (LDL-C, 160-189 mg/dL) and a family history of premature ASCVD, however, consider statin therapy. For patients with LDL-C ≥ 190 mg/dL, lifetime ASCVD risk is markedly increased, and high-intensity statin therapy is recommended, regardless of age. In this group, reassess ASCVD risk factors every 4 to 6 years.⁴

Continue to: > 75 years, without ASCVD

> 75 years, without ASCVD. In this group, the ­benefit of statin therapy is less clear and might be lessened by an increased potential for adverse effects. A meta-analysis of 28 trials demonstrated that people ages > 75 years had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C, which is comparable to the risk reduction seen in people ages 40 to 75 years.¹⁵

A meta-analysis of 28 trials demonstrated that people > 75 years of age had a 24% relative reduction in major coronary events for every 38.7 mg/dL (1.0 mmol/L) reduction in LDL-C.

With increasing age, however, the relative reduction in major coronary events with statin therapy decreased,¹⁵ although other trials have not demonstrated age heterogeneity.¹⁶ Because people > 75 years of age have a significantly higher ASCVD event rate, a comparable relative rate reduction with statin therapy results in a larger absolute rate reduction (ARR) and, therefore, a smaller number needed to treat (NNT) to prevent an event, compared to the NNT in younger people.

Secondary prevention

ACC/AHA guidelines define clinical ASCVD as a history of:

• acute coronary syndrome
• myocardial infarction
• coronary or other arterial revascularization
• cerebrovascular event
• symptomatic peripheral artery disease, including aortic aneurysm.

High-intensity statin therapy is indicated for all patients ≤ 75 years who have clinical ­ASCVD. In patients > 75 years, consider a taper to moderate-intensity statin therapy. An upper age limit for seeing benefit from statin therapy in secondary prevention has not been identified.⁴

Base a recommendation for preventive intervention, such as lipidlowering therapy, on the estimated 10-year risk for ASCVD.

In high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy, ezetimibe (discussed in the next section) can be added. In very-high-risk patients, if LDL-C remains ≥ 70 mg/dL despite maximally tolerated statin therapy plus ezetimibe, a proprotein convertase subtilisin/­kexin type 9 (PCSK9) inhibitor (also discussed next) can be added. Always precede initiation of a PCSK9 inhibitor with a discussion of the net benefit, safety, and cost with the patient.⁴

Continue to: Options for lipid-lowering pharmacotherapy

Statins (formally, hydroxymethylglutaryl-coenzyme A reductase inhibitors) offer the most predictable reduction in ASCVD risk of any lipid-lowering therapy. The evidence report that accompanied the 2016 USPSTF guidelines on statins for the prevention of cardiovascular disease (CVD) stated that low- or moderate-dosage statin therapy is associated with approximately a 30% relative risk reduction (RRR) in CVD events and CVD deaths and a 10% to 15% RRR in all-cause mortality.¹⁷

High-intensity statin therapy reduces LDL-C by ≥ 50%. Moderate-intensity statin therapy reduces LDL-C by 30% to 49% (TABLE 3).⁴

Statins are not without risk: A 2016 report¹⁸ estimated that treating 10,000 patients with a statin for 5 years would cause 1 case of rhabdomyolysis, 5 cases of myopathy, 75 new cases of diabetes, and 7 cases of hemorrhagic stroke. The same treatment would, however, avert approximately 1000 CVD events among patients with preexisting disease and approximately 500 CVD events among patients at elevated risk but without preexisting disease.¹⁸

Ezetimibe, a selective cholesterol-­absorption inhibitor, lowers LDL-C by 13% to 20% and typically is well tolerated. The use of ezetimibe in ASCVD risk reduction is supported by a single randomized controlled trial of more than 18,000 patients with recent acute coronary syndrome. Adding ezetimibe to simvastatin 40 mg resulted in a 2% absolute reduction in major adverse cardiovascular events over a median follow-up of 6 years (NNT = 50), compared to simvastatin alone.¹⁹ ACC/AHA guidelines recommend adding ezetimibe to maximally tolerated statin therapy in patients with clinical ASCVD who do not reach their goal LDL reduction with a statin alone. Ezetimibe also can be considered a statin alternative in patients who are statin intolerant.⁴

PCSK9 inhibitors. When added to statin therapy, evolocumab and alirocumab—monoclonal antibodies that inhibit PCSK9—offer an incremental decrease in LDL-C of approximately 60%.^20-22 In a meta-analysis of 35 trials evaluating the incremental benefit of PCSK9 inhibitor therapy, a significant reduction in cardiovascular events, including myocardial infarction (ARR = 1.3%; NNT = 77), stroke (ARR = 0.4%; NNT = 250), and coronary revascularization (ARR = 1.6%; NNT = 63) was reported. No significant difference was observed in all-cause or cardiovascular mortality.^21,23

Continue to: Inclisiran

Inclisiran, an injectable small-­interfering RNA that inhibits PCSK9 synthesis, provides an incremental decrease in LDL-C of > 50% in patients already receiving statin therapy. Meta-analysis of 3 small cardiovascular outcomes trials revealed no significant difference in the rate of myocardial infarction, stroke, or cardiovascular mortality with inclisiran compared to placebo. Larger outcomes trials are underway and might offer additional insight into this agent’s role in ASCVD risk management.²⁴

Omega-3 fatty acids. Multiple trials have demonstrated that adding omega-3 fatty acids to usual lipid-lowering therapy does not offer a consistent reduction in adverse cardiovascular outcomes, despite providing a significant reduction in TG levels. In a high-risk population with persistently elevated TG despite statin therapy, icosapent ethyl, a purified eicosapentaenoic acid ethyl ester, reduced major ASCVD outcomes by 25% over a median 4.9 years (ARR = 4.8%; NNT = 21), and cardiovascular death by 20% (ARR = 0.9%; NNT = 111), compared with a mineral oil placebo.²⁵ Subsequent trials, using a corn oil placebo, failed to duplicate these data²⁶—raising concern that the mineral oil comparator might have altered results of the eicosapentaenoic acid ethyl ester study.^27,28

Bempedoic acid is a small-molecule ­inhibitor of ATP citrate lyase that increases LDL uptake by the liver. Pooled data from studies of bempedoic acid show, on average, a 15% reduction in TC, a 23% reduction in LDL-C, and a 6% increase in HDL-C, without a significant change in TG.²⁹ In statin-­intolerant patients, bempedoic acid reduced major ASCVD outcomes by 13% over a median 40 months (ARR = 1.6%; NNT = 63), with no significant reduction in cardiovascular death.³⁰

Niacin. Two large trials failed to demonstrate improvement in major cardiovascular events or other clinical benefit when niacin is added to moderate-intensity statin therapy, despite a significant increase in the HDL-C level (on average, 6 mg/dL) and a decrease in the LDL-C level (10-12 mg/dL) and TG (42 mg/dL).^31,32

Fenofibrate lowers TG and increases HDL-C but does not consistently improve cardiovascular outcomes.³³ In a trial of patients with type 2 diabetes and persistent dyslipidemia (serum TG > 204 mg/dL; ­HDL-C < 34 mg/dL) despite statin therapy, adding fenofibrate reduced CVD outcomes by 4.9%—although this absolute difference did not reach statistical significance.³⁴

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.

Neither niacin nor fenofibrate is considered useful for reducing ASCVD risk across broad populations.⁴

Follow-up to assess progress toward goals

At-risk patients should follow a dietary pattern that emphasizes vegetables, fruits, and whole grains and limits sweets, sugarsweetened beverages, and red meat.

Recheck the lipid profile 4 to 12 weeks after starting lipid-lowering therapy to verify adherence to medication and assess response. The primary goal is the percentage reduction in LDL-C based on ASCVD risk. An additional goal for very-high-risk patients is an LDL-C value ≤ 70 mg/dL. If the reduction in LDL-C is less than desired and adherence is assured, consider titrating the statin dosage or augmenting statin therapy with a nonstatin drug (eg, ezetimibe), or both.⁴

CORRESPONDENCE
Jonathon M. Firnhaber, MD, MAEd, MBA, East Carolina University, Family Medicine Center, 101 Heart Drive, Greenville, NC 27834; [email protected]

Approximately 10,000 suicide deaths are recorded in Brazil every year. The suicide risk is highest among patients with depressive disorders, particularly women (> 18% vs. 11% for men).

There are countless people who work to prevent suicide, and the challenges they face are many. But now, on the horizon, there are new tools that could prove invaluable to their efforts – tools such as biomarkers. In a study recently published in the journal Frontiers in Psychiatry, researchers from the Catholic University of Pelotas (UCPel), Brazil, reported an association of glutathione (GSH) with the degree of suicide risk in women at 18 months postpartum. Specifically, they found that reduced serum GSH levels were significantly lower for those with moderate to high suicide risk than for those without suicide risk. Their findings suggest that GSH may be a potential biomarker or etiologic factor among women at risk for suicide, with therapeutic implications.

This was a case-control study nested within a cohort study. From this cohort, 45 women were selected at 18 months postpartum. Thirty of them had mood disorders, such as major depression and bipolar disorder. The other 15 participants, none of whom had a mood disorder, made up the control group.

Depression and the risk for suicide were assessed using the Mini International Neuropsychiatric Interview Plus (MINI-Plus 5.0.0 Brazilian version), module A and module C, respectively. Blood samples were collected to evaluate serum levels of the following oxidative stress biomarkers: reactive oxygen species, superoxide dismutase, and GSH.

The prevalence of suicide risk observed in the women at 18 months postpartum was 24.4%. The prevalence of suicide risk in the mood disorder group was 36.7%.

In addition, the statistical analysis found that women with moderate to high suicide risk had cerebral redox imbalance, resulting in a decrease in blood GSH levels.

The study team was led by neuroscientist Adriano Martimbianco de Assis, PhD, the coordinator of UCPel’s postgraduate program in health and behavior. He said that the correlation identified between GSH serum levels and suicide risk gives rise to two possible applications: using GSH as a biomarker for suicide risk and using GSH therapeutically.

Regarding the former application, Dr. Martimbianco de Assis explained that additional studies are needed to take a step forward. “Although we believe that most of the GSH came from the brain – given that it’s the brain’s main antioxidant – as we analyze blood samples, we’re not yet able to rule out the possibility that it came from other organs,” he said in an interview. So, confirming that hypothesis will require studies that involve imaging brain tissue. According to Dr. Martimbianco de Assis, once there is confirmation, it will be possible to move to using the antioxidant as a biomarker for suicide risk.

He also shared his views about the second application: using GSH therapeutically. “We already know that there are very simple alternatives that can influence GSH levels, [and they] mostly have to do with exercise and [improving the quality of] the food one eats. But there are also drugs: for example, N-acetyl cysteine, which is a precursor of GSH.” Adopting strategies to increase the levels of this antioxidant in the body should reverse the imbalance identified in the study and, as a result, may lead to lowering the risk for suicide. But, he reiterated, “getting to a place where GSH [can be used] in clinical practice hinges on getting that confirmation that it did, in fact, come from the brain. Recall that our study found lower levels of GSH in women at risk for suicide.”

Even though the study evaluated postpartum women, it’s possible that the results can be extrapolated to other populations, said Dr. Martimbianco de Assis. This is because when the data were collected, 18 months had already passed since giving birth. The participants’ physiological condition at that point was more similar to the one prior to becoming pregnant.

The UCPel researchers continue to follow the cohort. “We intend to continue monitoring GSH levels at other times. Forty-eight months have now passed since the women gave birth, and the idea is to continue studying [the patients involved in the study],” said Dr. Martimbianco de Assis, adding that the team also intends to analyze brain tissue from in vitro studies using cell cultures.

This article was translated from the Medscape Portuguese Edition and a version appeared on Medscape.com.

Approximately 10,000 suicide deaths are recorded in Brazil every year. The suicide risk is highest among patients with depressive disorders, particularly women (> 18% vs. 11% for men).

There are countless people who work to prevent suicide, and the challenges they face are many. But now, on the horizon, there are new tools that could prove invaluable to their efforts – tools such as biomarkers. In a study recently published in the journal Frontiers in Psychiatry, researchers from the Catholic University of Pelotas (UCPel), Brazil, reported an association of glutathione (GSH) with the degree of suicide risk in women at 18 months postpartum. Specifically, they found that reduced serum GSH levels were significantly lower for those with moderate to high suicide risk than for those without suicide risk. Their findings suggest that GSH may be a potential biomarker or etiologic factor among women at risk for suicide, with therapeutic implications.

This was a case-control study nested within a cohort study. From this cohort, 45 women were selected at 18 months postpartum. Thirty of them had mood disorders, such as major depression and bipolar disorder. The other 15 participants, none of whom had a mood disorder, made up the control group.

Depression and the risk for suicide were assessed using the Mini International Neuropsychiatric Interview Plus (MINI-Plus 5.0.0 Brazilian version), module A and module C, respectively. Blood samples were collected to evaluate serum levels of the following oxidative stress biomarkers: reactive oxygen species, superoxide dismutase, and GSH.

The prevalence of suicide risk observed in the women at 18 months postpartum was 24.4%. The prevalence of suicide risk in the mood disorder group was 36.7%.

In addition, the statistical analysis found that women with moderate to high suicide risk had cerebral redox imbalance, resulting in a decrease in blood GSH levels.

The study team was led by neuroscientist Adriano Martimbianco de Assis, PhD, the coordinator of UCPel’s postgraduate program in health and behavior. He said that the correlation identified between GSH serum levels and suicide risk gives rise to two possible applications: using GSH as a biomarker for suicide risk and using GSH therapeutically.

Regarding the former application, Dr. Martimbianco de Assis explained that additional studies are needed to take a step forward. “Although we believe that most of the GSH came from the brain – given that it’s the brain’s main antioxidant – as we analyze blood samples, we’re not yet able to rule out the possibility that it came from other organs,” he said in an interview. So, confirming that hypothesis will require studies that involve imaging brain tissue. According to Dr. Martimbianco de Assis, once there is confirmation, it will be possible to move to using the antioxidant as a biomarker for suicide risk.

He also shared his views about the second application: using GSH therapeutically. “We already know that there are very simple alternatives that can influence GSH levels, [and they] mostly have to do with exercise and [improving the quality of] the food one eats. But there are also drugs: for example, N-acetyl cysteine, which is a precursor of GSH.” Adopting strategies to increase the levels of this antioxidant in the body should reverse the imbalance identified in the study and, as a result, may lead to lowering the risk for suicide. But, he reiterated, “getting to a place where GSH [can be used] in clinical practice hinges on getting that confirmation that it did, in fact, come from the brain. Recall that our study found lower levels of GSH in women at risk for suicide.”

Even though the study evaluated postpartum women, it’s possible that the results can be extrapolated to other populations, said Dr. Martimbianco de Assis. This is because when the data were collected, 18 months had already passed since giving birth. The participants’ physiological condition at that point was more similar to the one prior to becoming pregnant.

The UCPel researchers continue to follow the cohort. “We intend to continue monitoring GSH levels at other times. Forty-eight months have now passed since the women gave birth, and the idea is to continue studying [the patients involved in the study],” said Dr. Martimbianco de Assis, adding that the team also intends to analyze brain tissue from in vitro studies using cell cultures.

This article was translated from the Medscape Portuguese Edition and a version appeared on Medscape.com.

Approximately 10,000 suicide deaths are recorded in Brazil every year. The suicide risk is highest among patients with depressive disorders, particularly women (> 18% vs. 11% for men).

There are countless people who work to prevent suicide, and the challenges they face are many. But now, on the horizon, there are new tools that could prove invaluable to their efforts – tools such as biomarkers. In a study recently published in the journal Frontiers in Psychiatry, researchers from the Catholic University of Pelotas (UCPel), Brazil, reported an association of glutathione (GSH) with the degree of suicide risk in women at 18 months postpartum. Specifically, they found that reduced serum GSH levels were significantly lower for those with moderate to high suicide risk than for those without suicide risk. Their findings suggest that GSH may be a potential biomarker or etiologic factor among women at risk for suicide, with therapeutic implications.

This was a case-control study nested within a cohort study. From this cohort, 45 women were selected at 18 months postpartum. Thirty of them had mood disorders, such as major depression and bipolar disorder. The other 15 participants, none of whom had a mood disorder, made up the control group.

Depression and the risk for suicide were assessed using the Mini International Neuropsychiatric Interview Plus (MINI-Plus 5.0.0 Brazilian version), module A and module C, respectively. Blood samples were collected to evaluate serum levels of the following oxidative stress biomarkers: reactive oxygen species, superoxide dismutase, and GSH.

The prevalence of suicide risk observed in the women at 18 months postpartum was 24.4%. The prevalence of suicide risk in the mood disorder group was 36.7%.

In addition, the statistical analysis found that women with moderate to high suicide risk had cerebral redox imbalance, resulting in a decrease in blood GSH levels.

The study team was led by neuroscientist Adriano Martimbianco de Assis, PhD, the coordinator of UCPel’s postgraduate program in health and behavior. He said that the correlation identified between GSH serum levels and suicide risk gives rise to two possible applications: using GSH as a biomarker for suicide risk and using GSH therapeutically.

Regarding the former application, Dr. Martimbianco de Assis explained that additional studies are needed to take a step forward. “Although we believe that most of the GSH came from the brain – given that it’s the brain’s main antioxidant – as we analyze blood samples, we’re not yet able to rule out the possibility that it came from other organs,” he said in an interview. So, confirming that hypothesis will require studies that involve imaging brain tissue. According to Dr. Martimbianco de Assis, once there is confirmation, it will be possible to move to using the antioxidant as a biomarker for suicide risk.

He also shared his views about the second application: using GSH therapeutically. “We already know that there are very simple alternatives that can influence GSH levels, [and they] mostly have to do with exercise and [improving the quality of] the food one eats. But there are also drugs: for example, N-acetyl cysteine, which is a precursor of GSH.” Adopting strategies to increase the levels of this antioxidant in the body should reverse the imbalance identified in the study and, as a result, may lead to lowering the risk for suicide. But, he reiterated, “getting to a place where GSH [can be used] in clinical practice hinges on getting that confirmation that it did, in fact, come from the brain. Recall that our study found lower levels of GSH in women at risk for suicide.”

Even though the study evaluated postpartum women, it’s possible that the results can be extrapolated to other populations, said Dr. Martimbianco de Assis. This is because when the data were collected, 18 months had already passed since giving birth. The participants’ physiological condition at that point was more similar to the one prior to becoming pregnant.

The UCPel researchers continue to follow the cohort. “We intend to continue monitoring GSH levels at other times. Forty-eight months have now passed since the women gave birth, and the idea is to continue studying [the patients involved in the study],” said Dr. Martimbianco de Assis, adding that the team also intends to analyze brain tissue from in vitro studies using cell cultures.

This article was translated from the Medscape Portuguese Edition and a version appeared on Medscape.com.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.

For women with excessive menstrual blood loss, the contraceptive levonorgestrel 52 mg delivered via an intrauterine device (IUD) reduced monthly blood loss by more than 90% over six monthly cycles, a multicenter open-label study reports.

Median blood loss decreased by more than 90% in the first three cycles. Overall, treatment was successful in 81.8% of 99 patients (95% confidence interval, 74.2%-89.4%), according to findings published in Obstetrics & Gynecology.

Racially diverse cohort

Conducted at 29 U.S. sites prior to seeking FDA registration for this new use, the phase 3 open-label trial of the 52 mg progestin-releasing IUD enrolled 105 participants with a mean age of 35.4 years. Unlike previous trials, this one included obese or severely obese women (44.8%), with 42 participants having a body mass index (BMI) of more than 35 kg/m², and also 28 nulliparous women (27.6%).

Those with abnormalities such as fibroids or coagulopathies were excluded. Although most of the cohort was White (n = 68), the study included Black (n = 25), Asian (n = 4), and Hispanic (n = 10) women, plus 7 from other minorities, suggesting the results would be widely applicable.

Mean baseline blood loss in the cohort ranged from 73 mL to 520 mL (median, 143 mL). Of 89 treated women with follow-up, participants had a median absolute blood-loss decreases of 93.3% (86.1%-97.8%) at cycle three and 97.6% (90.4%-100%) at cycle six. Median bleeding reductions at cycle six were similar between women with and without obesity at 97.6% and 97.5%, respectively, and between nulliparous and parous women at 97.0% and 98.1%, respectively (P = .43). The study, however, was not sufficiently powered to fully analyze these subgroups, the authors acknowledged.

Although results were overall comparable with those of a previous study on a different IUD, the expulsion rate was somewhat higher, at 9%, than the 6% reported in the earlier study.

Brigham and Women’s Hospital

“Although this strategy for reducing blood loss is not new, this study is notable because it looked at high-BMI women and nulliparous women,” said Kathryn J. Gray, MD, PhD, an attending physician in the department of obstetrics and gynecology at Brigham and Women’s Hospital in Boston, who was not involved in the research.“No prior trials have included patients with BMIs exceeding 35 kg/m² or nulliparous patients, while this study enrolled a full array of patients, which allowed exploratory analyses of these subpopulations,” Dr. Creinin confirmed.

According to Dr. Gray, the IUD approach has advantages over systemic treatment with oral medication. “First, treatment is not user-dependent so the user doesn’t have to remember to take it. In addition, because the medication is locally targeted in the uterus, it is more effective and there is less fluctuation and variability in drug levels than when taken orally.”

As to treatment durability, Dr. Creinin said, “Long-term studies in a population being treated for heavy menstrual bleeding would be helpful to have an idea of how long this effect lasts. Still, there is no reason to expect that the effect will not last for many years.”

And with this treatment, he added, both patient and clinician can readily detect its effect. “If bleeding begins to increase, they will know!”

Would there be a lingering residual effect even after removal of the IUD? “That is an excellent question that remains to be answered,” Dr. Creinin said. “There are no data on when the heavy bleeding returns, but it would be expected to do so.”

This study was funded, designed, and supervised by Medicines360, which also provided the study treatment. Dr. Creinin disclosed financial relationships with various private-sector companies, including Medicines360, Organon, Fuji Pharma, GlaxoSmithKline, and Merck & Co. Multiple study coauthors disclosed similar financial ties to industry partners, including Medicines360. Dr. Gray had no potential conflicts of interest with regard to her comments.