Clinician Reviews

New COVID boosters that target the fast-spreading Omicron strains of the virus are rolling out this week, with the Centers for Disease Control and Prevention recommending these bivalent mRNA shots for Americans 12 and older.

Here are answers to frequently asked questions about the shots produced by Moderna and Pfizer/BioNTech, based on information provided by the CDC and Keri Althoff, PhD, and virologist Andrew Pekosz, PhD, Johns Hopkins Bloomberg School of Public Health epidemiologists.

Question: Who is eligible for the new bivalent boosters?

Answer: The CDC greenlighted the upgraded Pfizer/BioNTech shots for Americans 12 and older and the Moderna booster for those 18 and over, if they have received a primary vaccine series or a booster at least 2 months before.

The boosters have been redesigned to protect against the predominant BA.4 and BA.5 strains of the virus. The Biden administration is making 160 million of the booster shots available free of charge through pharmacies, doctor’s offices, clinics, and state health departments.

Q: What about children under 12?

A: The new boosters are not approved for children under 12. Additional testing and trials need to be conducted for safety and effectiveness. But officials recommend that children 5 and above receive the primary vaccine series and be boosted with one shot. Children 6 months to under 5 years are not yet eligible for boosters.

Pfizer said it hopes to ask the Food and Drug Administration for authorization in 5- to 11-year-olds in October.

Q: How do the new bivalent boosters differ from previous shots?

A: The new shots use the same mRNA technology as the prior Moderna and Pfizer/BioNTech vaccines and boosters but have been upgraded to target the newer Omicron strains. The shots use mRNA created in a lab to teach our cells to produce a specific protein that triggers an immune-system response and make antibodies that help protect us from SARS-CoV-2, the virus that causes COVID.

The recipe for the new shots incorporates the so-called “spike protein” of both the original (ancestral) strain of the virus and more highly transmissible Omicron strains (BA.4, BA.5). Once your body produces these proteins, your immune system kicks into gear to mount a response.

It’s also possible – but yet to be determined – that the new bivalent boosters will offer protection against newer but less common strains known as BA.4.6 and BA.2.75.

Q: Are there any new risks or side effects associated with these boosters?

A: Health experts don’t expect to see anything beyond what has already been noted with prior mRNA vaccines, with the vast majority of recipients experiencing only mild issues such as redness from the shot, soreness, and fatigue.

Q: Do I need one of the new shots if I’ve already had past boosters or had COVID?

A: Yes. Even if you’ve been infected with COVID in the past year and/or received the prior series of primary vaccines and boosters, you should get a bivalent Omicron shot.

Doing so will give you broader immunity against COVID and also help limit the emergence of other variants. The more Americans with high immunity, the better; it makes it less likely other variants will emerge that can escape the immunity provided by vaccines and COVID infections.

Q: How long should I wait, from the time of my last shot, before getting a new booster?

A: The bivalent boosters are most effective when given after a period of time has passed between your last shot and the new one. A 2- to 3-month waiting period is the minimum, but some evidence suggests extending it out to 4-6 months might be good timing.

To determine when you should get a new booster, check out the CDC’s Stay Up to Date with COVID-19 Vaccines Including Boosters website.

Q: What if I’ve recently had COVID?

A: There are no specific rules about a waiting period after COVID infection. But if you have been infected with the virus in the last 8 weeks, you may want to wait for 8 weeks to pass before receiving the bivalent booster to allow your immune system to get greater benefit from the shot.

Q: If I never got the original vaccines, do I need to get those shots first?

A: Yes. The bivalent vaccine has a lower dose of mRNA than the vaccines used in the primary series of vaccines, rolled out in late 2020. The bivalent vaccine is authorized for use as a booster dose and not a primary vaccine series dose.

Q: Do the Omicron-specific boosters entirely replace the other boosters?

A: Yes. The new booster shots, which target the original strain and the Omicron subvariants, are now the only available boosters for people ages 12 and older. The FDA no longer authorizes the previous booster doses for people in the approved age groups.

Q: What if I received a non-mRNA vaccine produced by Novavax or Johnson & Johnson? Should I still get an mRNA booster?

A: You can mix and match COVID vaccines, and you are eligible to get the bivalent booster 8 weeks after completing the primary COVID vaccination series – whether that was two doses of mRNA or Novavax, or one shot of J&J.

Q: How effective are the new boosters?

A: Scientists don’t have complete effectiveness data from the bivalent vaccines yet. But because the new boosters contain mRNA from the Omicron and the original strains, they are believed to offer greater protection against COVID overall.

Cellular-level data support this, with studies showing the bivalent vaccines increase neutralizing antibodies to BA.4/BA.5 strains. Scientists regard these kinds of studies as surrogate stand-ins for clinical trials. But officials will be studying the effectiveness of the new boosters, examining to what degree they reduce hospitalizations and deaths.

Q: How long will the boosters’ protection last?

A: Research shows that vaccine effectiveness eventually wanes, which is why we have the boosters. Scientists will be monitoring to see how long the protection lasts from the bivalent boosters through studies of antibody levels as well as assessments of severe COVID illnesses over time, throughout the fall and winter.

Q: Is it OK to get a flu shot and a COVID booster at the same time?

A: Yes. In fact, it’s important to get a flu shot this year because some experts believe we could see overlapping COVID-influenza surges this fall – a phenomenon some have fancifully called a “twindemic.” Getting a flu shot and COVID booster – simultaneously, if possible – is particularly important if you’re in a high-risk group.

People who are susceptible to severe complications from COVID – such as older people, people with weakened immune systems, and those with chronic health conditions – are also especially vulnerable to severe influenza complications.

Q: Will a new booster mean I can stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID?

A: No. It’s still a good idea to mask up, keep your distance from others, avoid indoor spaces with people whose vaccine status is unknown, and take other precautions against COVID.

Although the new boosters are front of mind, it’s a good idea to also use other tools in the toolbox, as well, particularly if you have contact with someone who is older, immune-suppressed, or has a chronic condition that puts them at higher risk from COVID.

Keep in mind: The community risk of infection nationwide is still high today, with about 67,400 new cases and nearly 320 deaths reported each day in the United States, according to the latest CDC reports.A version of this article first appeared on WebMD.

New COVID boosters that target the fast-spreading Omicron strains of the virus are rolling out this week, with the Centers for Disease Control and Prevention recommending these bivalent mRNA shots for Americans 12 and older.

Here are answers to frequently asked questions about the shots produced by Moderna and Pfizer/BioNTech, based on information provided by the CDC and Keri Althoff, PhD, and virologist Andrew Pekosz, PhD, Johns Hopkins Bloomberg School of Public Health epidemiologists.

Question: Who is eligible for the new bivalent boosters?

Answer: The CDC greenlighted the upgraded Pfizer/BioNTech shots for Americans 12 and older and the Moderna booster for those 18 and over, if they have received a primary vaccine series or a booster at least 2 months before.

The boosters have been redesigned to protect against the predominant BA.4 and BA.5 strains of the virus. The Biden administration is making 160 million of the booster shots available free of charge through pharmacies, doctor’s offices, clinics, and state health departments.

Q: What about children under 12?

A: The new boosters are not approved for children under 12. Additional testing and trials need to be conducted for safety and effectiveness. But officials recommend that children 5 and above receive the primary vaccine series and be boosted with one shot. Children 6 months to under 5 years are not yet eligible for boosters.

Pfizer said it hopes to ask the Food and Drug Administration for authorization in 5- to 11-year-olds in October.

Q: How do the new bivalent boosters differ from previous shots?

A: The new shots use the same mRNA technology as the prior Moderna and Pfizer/BioNTech vaccines and boosters but have been upgraded to target the newer Omicron strains. The shots use mRNA created in a lab to teach our cells to produce a specific protein that triggers an immune-system response and make antibodies that help protect us from SARS-CoV-2, the virus that causes COVID.

The recipe for the new shots incorporates the so-called “spike protein” of both the original (ancestral) strain of the virus and more highly transmissible Omicron strains (BA.4, BA.5). Once your body produces these proteins, your immune system kicks into gear to mount a response.

It’s also possible – but yet to be determined – that the new bivalent boosters will offer protection against newer but less common strains known as BA.4.6 and BA.2.75.

Q: Are there any new risks or side effects associated with these boosters?

A: Health experts don’t expect to see anything beyond what has already been noted with prior mRNA vaccines, with the vast majority of recipients experiencing only mild issues such as redness from the shot, soreness, and fatigue.

Q: Do I need one of the new shots if I’ve already had past boosters or had COVID?

A: Yes. Even if you’ve been infected with COVID in the past year and/or received the prior series of primary vaccines and boosters, you should get a bivalent Omicron shot.

Doing so will give you broader immunity against COVID and also help limit the emergence of other variants. The more Americans with high immunity, the better; it makes it less likely other variants will emerge that can escape the immunity provided by vaccines and COVID infections.

Q: How long should I wait, from the time of my last shot, before getting a new booster?

A: The bivalent boosters are most effective when given after a period of time has passed between your last shot and the new one. A 2- to 3-month waiting period is the minimum, but some evidence suggests extending it out to 4-6 months might be good timing.

To determine when you should get a new booster, check out the CDC’s Stay Up to Date with COVID-19 Vaccines Including Boosters website.

Q: What if I’ve recently had COVID?

A: There are no specific rules about a waiting period after COVID infection. But if you have been infected with the virus in the last 8 weeks, you may want to wait for 8 weeks to pass before receiving the bivalent booster to allow your immune system to get greater benefit from the shot.

Q: If I never got the original vaccines, do I need to get those shots first?

A: Yes. The bivalent vaccine has a lower dose of mRNA than the vaccines used in the primary series of vaccines, rolled out in late 2020. The bivalent vaccine is authorized for use as a booster dose and not a primary vaccine series dose.

Q: Do the Omicron-specific boosters entirely replace the other boosters?

A: Yes. The new booster shots, which target the original strain and the Omicron subvariants, are now the only available boosters for people ages 12 and older. The FDA no longer authorizes the previous booster doses for people in the approved age groups.

Q: What if I received a non-mRNA vaccine produced by Novavax or Johnson & Johnson? Should I still get an mRNA booster?

A: You can mix and match COVID vaccines, and you are eligible to get the bivalent booster 8 weeks after completing the primary COVID vaccination series – whether that was two doses of mRNA or Novavax, or one shot of J&J.

Q: How effective are the new boosters?

A: Scientists don’t have complete effectiveness data from the bivalent vaccines yet. But because the new boosters contain mRNA from the Omicron and the original strains, they are believed to offer greater protection against COVID overall.

Cellular-level data support this, with studies showing the bivalent vaccines increase neutralizing antibodies to BA.4/BA.5 strains. Scientists regard these kinds of studies as surrogate stand-ins for clinical trials. But officials will be studying the effectiveness of the new boosters, examining to what degree they reduce hospitalizations and deaths.

Q: How long will the boosters’ protection last?

A: Research shows that vaccine effectiveness eventually wanes, which is why we have the boosters. Scientists will be monitoring to see how long the protection lasts from the bivalent boosters through studies of antibody levels as well as assessments of severe COVID illnesses over time, throughout the fall and winter.

Q: Is it OK to get a flu shot and a COVID booster at the same time?

A: Yes. In fact, it’s important to get a flu shot this year because some experts believe we could see overlapping COVID-influenza surges this fall – a phenomenon some have fancifully called a “twindemic.” Getting a flu shot and COVID booster – simultaneously, if possible – is particularly important if you’re in a high-risk group.

People who are susceptible to severe complications from COVID – such as older people, people with weakened immune systems, and those with chronic health conditions – are also especially vulnerable to severe influenza complications.

Q: Will a new booster mean I can stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID?

A: No. It’s still a good idea to mask up, keep your distance from others, avoid indoor spaces with people whose vaccine status is unknown, and take other precautions against COVID.

Although the new boosters are front of mind, it’s a good idea to also use other tools in the toolbox, as well, particularly if you have contact with someone who is older, immune-suppressed, or has a chronic condition that puts them at higher risk from COVID.

Keep in mind: The community risk of infection nationwide is still high today, with about 67,400 new cases and nearly 320 deaths reported each day in the United States, according to the latest CDC reports.A version of this article first appeared on WebMD.

New COVID boosters that target the fast-spreading Omicron strains of the virus are rolling out this week, with the Centers for Disease Control and Prevention recommending these bivalent mRNA shots for Americans 12 and older.

Here are answers to frequently asked questions about the shots produced by Moderna and Pfizer/BioNTech, based on information provided by the CDC and Keri Althoff, PhD, and virologist Andrew Pekosz, PhD, Johns Hopkins Bloomberg School of Public Health epidemiologists.

Question: Who is eligible for the new bivalent boosters?

Answer: The CDC greenlighted the upgraded Pfizer/BioNTech shots for Americans 12 and older and the Moderna booster for those 18 and over, if they have received a primary vaccine series or a booster at least 2 months before.

The boosters have been redesigned to protect against the predominant BA.4 and BA.5 strains of the virus. The Biden administration is making 160 million of the booster shots available free of charge through pharmacies, doctor’s offices, clinics, and state health departments.

Q: What about children under 12?

A: The new boosters are not approved for children under 12. Additional testing and trials need to be conducted for safety and effectiveness. But officials recommend that children 5 and above receive the primary vaccine series and be boosted with one shot. Children 6 months to under 5 years are not yet eligible for boosters.

Pfizer said it hopes to ask the Food and Drug Administration for authorization in 5- to 11-year-olds in October.

Q: How do the new bivalent boosters differ from previous shots?

A: The new shots use the same mRNA technology as the prior Moderna and Pfizer/BioNTech vaccines and boosters but have been upgraded to target the newer Omicron strains. The shots use mRNA created in a lab to teach our cells to produce a specific protein that triggers an immune-system response and make antibodies that help protect us from SARS-CoV-2, the virus that causes COVID.

The recipe for the new shots incorporates the so-called “spike protein” of both the original (ancestral) strain of the virus and more highly transmissible Omicron strains (BA.4, BA.5). Once your body produces these proteins, your immune system kicks into gear to mount a response.

It’s also possible – but yet to be determined – that the new bivalent boosters will offer protection against newer but less common strains known as BA.4.6 and BA.2.75.

Q: Are there any new risks or side effects associated with these boosters?

A: Health experts don’t expect to see anything beyond what has already been noted with prior mRNA vaccines, with the vast majority of recipients experiencing only mild issues such as redness from the shot, soreness, and fatigue.

Q: Do I need one of the new shots if I’ve already had past boosters or had COVID?

A: Yes. Even if you’ve been infected with COVID in the past year and/or received the prior series of primary vaccines and boosters, you should get a bivalent Omicron shot.

Doing so will give you broader immunity against COVID and also help limit the emergence of other variants. The more Americans with high immunity, the better; it makes it less likely other variants will emerge that can escape the immunity provided by vaccines and COVID infections.

Q: How long should I wait, from the time of my last shot, before getting a new booster?

A: The bivalent boosters are most effective when given after a period of time has passed between your last shot and the new one. A 2- to 3-month waiting period is the minimum, but some evidence suggests extending it out to 4-6 months might be good timing.

To determine when you should get a new booster, check out the CDC’s Stay Up to Date with COVID-19 Vaccines Including Boosters website.

Q: What if I’ve recently had COVID?

A: There are no specific rules about a waiting period after COVID infection. But if you have been infected with the virus in the last 8 weeks, you may want to wait for 8 weeks to pass before receiving the bivalent booster to allow your immune system to get greater benefit from the shot.

Q: If I never got the original vaccines, do I need to get those shots first?

A: Yes. The bivalent vaccine has a lower dose of mRNA than the vaccines used in the primary series of vaccines, rolled out in late 2020. The bivalent vaccine is authorized for use as a booster dose and not a primary vaccine series dose.

Q: Do the Omicron-specific boosters entirely replace the other boosters?

A: Yes. The new booster shots, which target the original strain and the Omicron subvariants, are now the only available boosters for people ages 12 and older. The FDA no longer authorizes the previous booster doses for people in the approved age groups.

Q: What if I received a non-mRNA vaccine produced by Novavax or Johnson & Johnson? Should I still get an mRNA booster?

A: You can mix and match COVID vaccines, and you are eligible to get the bivalent booster 8 weeks after completing the primary COVID vaccination series – whether that was two doses of mRNA or Novavax, or one shot of J&J.

Q: How effective are the new boosters?

A: Scientists don’t have complete effectiveness data from the bivalent vaccines yet. But because the new boosters contain mRNA from the Omicron and the original strains, they are believed to offer greater protection against COVID overall.

Cellular-level data support this, with studies showing the bivalent vaccines increase neutralizing antibodies to BA.4/BA.5 strains. Scientists regard these kinds of studies as surrogate stand-ins for clinical trials. But officials will be studying the effectiveness of the new boosters, examining to what degree they reduce hospitalizations and deaths.

Q: How long will the boosters’ protection last?

A: Research shows that vaccine effectiveness eventually wanes, which is why we have the boosters. Scientists will be monitoring to see how long the protection lasts from the bivalent boosters through studies of antibody levels as well as assessments of severe COVID illnesses over time, throughout the fall and winter.

Q: Is it OK to get a flu shot and a COVID booster at the same time?

A: Yes. In fact, it’s important to get a flu shot this year because some experts believe we could see overlapping COVID-influenza surges this fall – a phenomenon some have fancifully called a “twindemic.” Getting a flu shot and COVID booster – simultaneously, if possible – is particularly important if you’re in a high-risk group.

People who are susceptible to severe complications from COVID – such as older people, people with weakened immune systems, and those with chronic health conditions – are also especially vulnerable to severe influenza complications.

Q: Will a new booster mean I can stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID?

A: No. It’s still a good idea to mask up, keep your distance from others, avoid indoor spaces with people whose vaccine status is unknown, and take other precautions against COVID.

Although the new boosters are front of mind, it’s a good idea to also use other tools in the toolbox, as well, particularly if you have contact with someone who is older, immune-suppressed, or has a chronic condition that puts them at higher risk from COVID.

Keep in mind: The community risk of infection nationwide is still high today, with about 67,400 new cases and nearly 320 deaths reported each day in the United States, according to the latest CDC reports.A version of this article first appeared on WebMD.

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

Chronic lack of exercise – dubbed “exercise deficiency” – is associated with cardiac atrophy, reduced cardiac output and chamber size, and diminished cardiorespiratory fitness (CRF) in a subgroup of patients with heart failure with preserved ejection fraction (HFpEF), researchers say.

Increasing the physical activity levels of these sedentary individuals could be an effective preventive strategy, particularly for those who are younger and middle-aged, they suggest.

Thinking of HFpEF as an exercise deficiency syndrome leading to a small heart “flies in the face of decades of cardiovascular teaching, because traditionally, we’ve thought of heart failure as the big floppy heart,” Andre La Gerche, MBBS, PhD, of the Baker Heart and Diabetes Institute, Melbourne, told this news organization.

“While it is true that some people with HFpEF have thick, stiff hearts, we propose that another subset has a normal heart, except it’s small because it’s been underexercised,” he said.

The article, published online  as part of a Focus Seminar series in the Journal of the American College of Cardiology, has “gone viral on social media,” Jason C. Kovacic, MBBS, PhD, of the Victor Chang Cardiac Research Institute, Darlinghurst, Australia, told this news organization.

Dr. Kovacic is a JACC section editor and the coordinating and senior author of the series, which covers other issues surrounding physical activity, both in athletes and the general public.
 

‘Coin-dropping moment’

To support their hypothesis that HFpEF is an exercise deficiency in certain patients, Dr. La Gerche and colleagues conducted a literature review that highlights the following points:

• There is a strong association between physical activity and both CRF and heart function.
• Exercise deficiency is a major risk factor for HFpEF in a subset of patients.
• Increasing physical activity is associated with greater cardiac mass, stroke volumes, cardiac output, and peak oxygen consumption.
• Physical inactivity leads to loss of heart muscle, reduced output and chamber size, and less ability to improve cardiac performance with exercise.
• Aging results in a smaller, stiffer heart; however, this effect is mitigated by regular exercise.
• Individuals who are sedentary throughout life cannot attenuate age-related reductions in heart size and have increasing chamber stiffness.

“When we explain it, it’s like a coin-dropping moment, because it’s actually a really simple concept,” Dr. La Gerche said. “A small heart has a small stroke volume. A patient with a small heart with a maximal stroke volume of 60 mL can generate a cardiac output of 9 L/min at a heart rate of 150 beats/min during exercise – an output that just isn’t enough. It’s like trying to drive a truck with a 50cc motorbike engine.”

“Plus,” Dr. La Gerche added, “exercise deficiency also sets the stage for comorbidities such as obesity, diabetes, and high blood pressure, all of which can ultimately lead to HFpEF.”

Considering HFpEF as an exercise deficiency syndrome has two clinical implications, Dr. La Gerche said. “First, it helps us understand the condition and diagnose more cases. For example, I think practitioners will start to recognize that breathlessness in some of their patients is associated with a small heart.”

“Second,” he said, “if it’s an exercise deficiency syndrome, the treatment is exercise. For most people, that means exercising regularly before the age of 60 to prevent HFpEF, because studies have found that after the age of 60, the heart is a bit fixed and harder to remodel. That doesn’t mean you shouldn’t try after 60 or that you won’t get benefit. But the real sweet spot is in middle age and younger.”
 

The bigger picture

The JACC Focus Seminar series starts with an article that underscores the benefits of regular physical activity. “The key is getting our patients to meet the guidelines: 150 to 300 minutes of moderate intensity exercise per week, or 75 to 250 minutes of vigorous activity per week,” Dr. Kovacic emphasized.

“Yes, we can give a statin to lower cholesterol. Yes, we can give a blood pressure medication to lower blood pressure. But when you prescribe exercise, you impact patients’ blood pressure, their cholesterol, their weight, their sense of well-being,” he said. “It cuts across so many different aspects of people’s lives that it’s important to underscore the value of exercise to everybody.”

That includes physicians, he affirmed. “It behooves all physicians to be leading by example. I would encourage those who are overweight or aren’t exercising as much as they should be to make the time to be healthy and to exercise. If you don’t, then bad health will force you to make the time to deal with bad health issues.”

Other articles in the series deal with the athlete’s heart. Christopher Semsarian, MBBS, PhD, MPH, University of Sydney, and colleagues discuss emerging data on hypertrophic cardiomyopathy and other genetic cardiovascular diseases, with the conclusion that it is probably okay for more athletes with these conditions to participate in recreational and competitive sports than was previously thought – another paradigm shift, according to Dr. Kovacic.

The final article addresses some of the challenges and controversies related to the athlete’s heart, including whether extreme exercise is associated with vulnerability to atrial fibrillation and other arrhythmias, and the impact of gender on the cardiac response to exercise, which can’t be determined now because of a paucity of data on women in sports.

Overall, Dr. Kovacic said, the series makes for “compelling” reading that should encourage readers to embark on their own studies to add to the data and support exercise prescription across the board.

No commercial funding or relevant conflicts of interest were reported.

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

A new study provides yet more evidence that a significant subset of people who experience persistent fatigue and exercise intolerance following COVID-19 will meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Data from the prospective observational study of 42 patients with “post-COVID-19 syndrome (PCS),” including persistent fatigue and exercise intolerance, suggest that a large proportion will meet strict diagnostic criteria for ME/CFS, including the hallmark postexertional malaise (PEM). Still others may experience similar disability but lack duration and/or severity requirements for the diagnosis.

Moreover, disease severity and symptom burden were found similar in those with ME/CFS following COVID-19 and in a group of 19 age- and sex-matched individuals with ME/CFS that wasn’t associated with COVID-19.

“The major finding is that ME/CFS is indeed part of the spectrum of the post-COVID syndrome and very similar to the ME/CFS we know after other infectious triggers,” senior author Carmen Scheibenbogen, MD, acting director of the Institute for Medical Immunology at the Charité University Medicine Campus Virchow-Klinikum, Berlin, told this news organization.

Importantly, from a clinical standpoint, both diminished hand-grip strength (HGS) and orthostatic intolerance were common across all patient groups, as were several laboratory values, Claudia Kedor, MD, and colleagues at Charité report in the paper, published online in Nature Communications.

Of the 42 with PCS, including persistent fatigue and exercise intolerance lasting at least 6 months, 19 met the rigorous Canadian Consensus Criteria (CCC) for ME/CFS, established in 2003, which require PEM, along with sleep dysfunction, significant persistent fatigue, pain, and several other symptoms from neurological/cognitive, autonomic, neuroendocrine, and immune categories that persist for at least 6 months.

Of the 23 who did not meet the CCC criteria, 18 still experienced PEM but for less than the required 14 hours set by the authors based on recent data. The original CCC had suggested 24 hours as the PEM duration. Eight subjects met all the Canadian criteria except for the neurological/cognitive symptoms. None of the 42 had evidence of severe depression.

The previously widely used 1994 “Fukuda” criteria for ME/CFS are no longer recommended because they don’t require PEM, which is now considered a key symptom. The more recent 2015 Institute (now Academy) of Medicine criteria don’t define the length of PEM, the authors note in the paper.

Dr. Scheibenbogen said, “Post-COVID has a spectrum of syndromes and conditions. We see that a subset of patients have similar symptoms of ME/CFS but don’t fulfill the CCC, although they may meet less stringent criteria. We think this is of relevance for both diagnostic markers and development of therapy, because there may be different pathomechanisms between the subsets of post-COVID patients.”

She pointed to other studies from her group suggesting that inflammation is present early in post-COVID (not yet published), while in the subset that goes on to ME/CFS, autoantibodies or endothelial dysfunction play a more important role. «At the moment, it’s quite complex, and I don’t think in the end we will have just one pathomechanism. So I think we’ll need to develop various treatment strategies.”

Asked to comment on the new data, Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital, both in Boston, and editor in chief of the Harvard Health Letter, told this news organization, “This paper adds to the evidence that an illness with symptoms that meet criteria for ME/CFS can follow COVID-19 in nearly half of those patients who have lingering symptoms. This can occur even in people who initially have only mild symptoms from COVID-19, although it is more likely to happen in the people who are sickest when they first get COVID-19. And those who meet criteria for ME/CFS were seriously impaired in their ability to function, [both] at work and at home.”

But, Dr. Komaroff also cautioned, “the study does not help in determining what fraction of all people who are infected with SARS-CoV-2 go on to develop a condition like ME/CFS, nor how long that condition will last. It is crucial that we get answers to these questions, as the impact on the economy, the health care system, and the disability system could be substantial.”

He pointed to a recent report from the Brookings Institution (2022 Aug 24. “New data shows long Covid is keeping as many as 4 million people out of work” Katie Bach) “finding that “long COVID may be a major contributor to the shortage of job applicants plaguing many businesses.”
 

Biomarkers include hand-grip strength, orthostatic intolerance, lab measures

Hand-grip strength, as assessed by 10 repeat grips at maximum force and repeated after 60 minutes, were lower for all those meeting ME/CFS criteria, compared with the healthy controls. Hand-grip strength parameters were also positively correlated with laboratory hemoglobin measures in both PCS groups who did and didn’t meet the Canadian ME/CFS criteria.

A total of three patients with PCS who didn’t meet ME/CFS criteria and seven with PCS who met ME/CFS criteria had sitting blood pressures of greater than 140 mm Hg systolic and/or greater than 90 mm Hg diastolic. Five patients with PCS – four who met ME/CFS criteria and one who didn’t – fulfilled criteria for postural orthostatic tachycardia syndrome. Orthostatic hypotension was diagnosed in a total of seven with PCS, including one who did not meet ME/CFS criteria and the rest who did.

Among significant laboratory findings, mannose-binding lectin deficiency, which is associated with increased infection susceptibility and found in only about 6% of historical controls, was found more frequently in both of the PCS cohorts (17% of those with ME/CFS and 23% of those without) than it has been in the past among those with ME/CFS, compared with historical controls (15%).

There was only slight elevation in C-reactive protein, the most commonly measured marker of inflammation. However, another marker indicating inflammation within the last 3-4 months, interleukin 8 assessed in erythrocytes, was above normal in 37% with PCS and ME/CFS and in 48% with PCS who did not meet the ME/CFS criteria.

Elevated antinuclear antibodies, anti–thyroid peroxidase antibodies, vitamin D deficiencies, and folic acid deficiencies were all seen in small numbers of the PCS patients. Angiotensin-converting enzyme 1 levels were below the normal range in 31% of all patients.

“We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients,” Dr. Kedor and colleagues write. “At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis. Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.”

Dr. Scheibenbogen and Dr. Komaroff reported no relevant financial relationships.

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

A new study provides yet more evidence that a significant subset of people who experience persistent fatigue and exercise intolerance following COVID-19 will meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Data from the prospective observational study of 42 patients with “post-COVID-19 syndrome (PCS),” including persistent fatigue and exercise intolerance, suggest that a large proportion will meet strict diagnostic criteria for ME/CFS, including the hallmark postexertional malaise (PEM). Still others may experience similar disability but lack duration and/or severity requirements for the diagnosis.

Moreover, disease severity and symptom burden were found similar in those with ME/CFS following COVID-19 and in a group of 19 age- and sex-matched individuals with ME/CFS that wasn’t associated with COVID-19.

“The major finding is that ME/CFS is indeed part of the spectrum of the post-COVID syndrome and very similar to the ME/CFS we know after other infectious triggers,” senior author Carmen Scheibenbogen, MD, acting director of the Institute for Medical Immunology at the Charité University Medicine Campus Virchow-Klinikum, Berlin, told this news organization.

Importantly, from a clinical standpoint, both diminished hand-grip strength (HGS) and orthostatic intolerance were common across all patient groups, as were several laboratory values, Claudia Kedor, MD, and colleagues at Charité report in the paper, published online in Nature Communications.

Of the 42 with PCS, including persistent fatigue and exercise intolerance lasting at least 6 months, 19 met the rigorous Canadian Consensus Criteria (CCC) for ME/CFS, established in 2003, which require PEM, along with sleep dysfunction, significant persistent fatigue, pain, and several other symptoms from neurological/cognitive, autonomic, neuroendocrine, and immune categories that persist for at least 6 months.

Of the 23 who did not meet the CCC criteria, 18 still experienced PEM but for less than the required 14 hours set by the authors based on recent data. The original CCC had suggested 24 hours as the PEM duration. Eight subjects met all the Canadian criteria except for the neurological/cognitive symptoms. None of the 42 had evidence of severe depression.

The previously widely used 1994 “Fukuda” criteria for ME/CFS are no longer recommended because they don’t require PEM, which is now considered a key symptom. The more recent 2015 Institute (now Academy) of Medicine criteria don’t define the length of PEM, the authors note in the paper.

Dr. Scheibenbogen said, “Post-COVID has a spectrum of syndromes and conditions. We see that a subset of patients have similar symptoms of ME/CFS but don’t fulfill the CCC, although they may meet less stringent criteria. We think this is of relevance for both diagnostic markers and development of therapy, because there may be different pathomechanisms between the subsets of post-COVID patients.”

She pointed to other studies from her group suggesting that inflammation is present early in post-COVID (not yet published), while in the subset that goes on to ME/CFS, autoantibodies or endothelial dysfunction play a more important role. «At the moment, it’s quite complex, and I don’t think in the end we will have just one pathomechanism. So I think we’ll need to develop various treatment strategies.”

Asked to comment on the new data, Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital, both in Boston, and editor in chief of the Harvard Health Letter, told this news organization, “This paper adds to the evidence that an illness with symptoms that meet criteria for ME/CFS can follow COVID-19 in nearly half of those patients who have lingering symptoms. This can occur even in people who initially have only mild symptoms from COVID-19, although it is more likely to happen in the people who are sickest when they first get COVID-19. And those who meet criteria for ME/CFS were seriously impaired in their ability to function, [both] at work and at home.”

But, Dr. Komaroff also cautioned, “the study does not help in determining what fraction of all people who are infected with SARS-CoV-2 go on to develop a condition like ME/CFS, nor how long that condition will last. It is crucial that we get answers to these questions, as the impact on the economy, the health care system, and the disability system could be substantial.”

He pointed to a recent report from the Brookings Institution (2022 Aug 24. “New data shows long Covid is keeping as many as 4 million people out of work” Katie Bach) “finding that “long COVID may be a major contributor to the shortage of job applicants plaguing many businesses.”
 

Biomarkers include hand-grip strength, orthostatic intolerance, lab measures

Hand-grip strength, as assessed by 10 repeat grips at maximum force and repeated after 60 minutes, were lower for all those meeting ME/CFS criteria, compared with the healthy controls. Hand-grip strength parameters were also positively correlated with laboratory hemoglobin measures in both PCS groups who did and didn’t meet the Canadian ME/CFS criteria.

A total of three patients with PCS who didn’t meet ME/CFS criteria and seven with PCS who met ME/CFS criteria had sitting blood pressures of greater than 140 mm Hg systolic and/or greater than 90 mm Hg diastolic. Five patients with PCS – four who met ME/CFS criteria and one who didn’t – fulfilled criteria for postural orthostatic tachycardia syndrome. Orthostatic hypotension was diagnosed in a total of seven with PCS, including one who did not meet ME/CFS criteria and the rest who did.

Among significant laboratory findings, mannose-binding lectin deficiency, which is associated with increased infection susceptibility and found in only about 6% of historical controls, was found more frequently in both of the PCS cohorts (17% of those with ME/CFS and 23% of those without) than it has been in the past among those with ME/CFS, compared with historical controls (15%).

There was only slight elevation in C-reactive protein, the most commonly measured marker of inflammation. However, another marker indicating inflammation within the last 3-4 months, interleukin 8 assessed in erythrocytes, was above normal in 37% with PCS and ME/CFS and in 48% with PCS who did not meet the ME/CFS criteria.

Elevated antinuclear antibodies, anti–thyroid peroxidase antibodies, vitamin D deficiencies, and folic acid deficiencies were all seen in small numbers of the PCS patients. Angiotensin-converting enzyme 1 levels were below the normal range in 31% of all patients.

“We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients,” Dr. Kedor and colleagues write. “At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis. Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.”

Dr. Scheibenbogen and Dr. Komaroff reported no relevant financial relationships.

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

A new study provides yet more evidence that a significant subset of people who experience persistent fatigue and exercise intolerance following COVID-19 will meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Data from the prospective observational study of 42 patients with “post-COVID-19 syndrome (PCS),” including persistent fatigue and exercise intolerance, suggest that a large proportion will meet strict diagnostic criteria for ME/CFS, including the hallmark postexertional malaise (PEM). Still others may experience similar disability but lack duration and/or severity requirements for the diagnosis.

Moreover, disease severity and symptom burden were found similar in those with ME/CFS following COVID-19 and in a group of 19 age- and sex-matched individuals with ME/CFS that wasn’t associated with COVID-19.

“The major finding is that ME/CFS is indeed part of the spectrum of the post-COVID syndrome and very similar to the ME/CFS we know after other infectious triggers,” senior author Carmen Scheibenbogen, MD, acting director of the Institute for Medical Immunology at the Charité University Medicine Campus Virchow-Klinikum, Berlin, told this news organization.

Importantly, from a clinical standpoint, both diminished hand-grip strength (HGS) and orthostatic intolerance were common across all patient groups, as were several laboratory values, Claudia Kedor, MD, and colleagues at Charité report in the paper, published online in Nature Communications.

Of the 42 with PCS, including persistent fatigue and exercise intolerance lasting at least 6 months, 19 met the rigorous Canadian Consensus Criteria (CCC) for ME/CFS, established in 2003, which require PEM, along with sleep dysfunction, significant persistent fatigue, pain, and several other symptoms from neurological/cognitive, autonomic, neuroendocrine, and immune categories that persist for at least 6 months.

Of the 23 who did not meet the CCC criteria, 18 still experienced PEM but for less than the required 14 hours set by the authors based on recent data. The original CCC had suggested 24 hours as the PEM duration. Eight subjects met all the Canadian criteria except for the neurological/cognitive symptoms. None of the 42 had evidence of severe depression.

The previously widely used 1994 “Fukuda” criteria for ME/CFS are no longer recommended because they don’t require PEM, which is now considered a key symptom. The more recent 2015 Institute (now Academy) of Medicine criteria don’t define the length of PEM, the authors note in the paper.

Dr. Scheibenbogen said, “Post-COVID has a spectrum of syndromes and conditions. We see that a subset of patients have similar symptoms of ME/CFS but don’t fulfill the CCC, although they may meet less stringent criteria. We think this is of relevance for both diagnostic markers and development of therapy, because there may be different pathomechanisms between the subsets of post-COVID patients.”

She pointed to other studies from her group suggesting that inflammation is present early in post-COVID (not yet published), while in the subset that goes on to ME/CFS, autoantibodies or endothelial dysfunction play a more important role. «At the moment, it’s quite complex, and I don’t think in the end we will have just one pathomechanism. So I think we’ll need to develop various treatment strategies.”

Asked to comment on the new data, Anthony L. Komaroff, MD, professor of medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital, both in Boston, and editor in chief of the Harvard Health Letter, told this news organization, “This paper adds to the evidence that an illness with symptoms that meet criteria for ME/CFS can follow COVID-19 in nearly half of those patients who have lingering symptoms. This can occur even in people who initially have only mild symptoms from COVID-19, although it is more likely to happen in the people who are sickest when they first get COVID-19. And those who meet criteria for ME/CFS were seriously impaired in their ability to function, [both] at work and at home.”

But, Dr. Komaroff also cautioned, “the study does not help in determining what fraction of all people who are infected with SARS-CoV-2 go on to develop a condition like ME/CFS, nor how long that condition will last. It is crucial that we get answers to these questions, as the impact on the economy, the health care system, and the disability system could be substantial.”

He pointed to a recent report from the Brookings Institution (2022 Aug 24. “New data shows long Covid is keeping as many as 4 million people out of work” Katie Bach) “finding that “long COVID may be a major contributor to the shortage of job applicants plaguing many businesses.”
 

Biomarkers include hand-grip strength, orthostatic intolerance, lab measures

Hand-grip strength, as assessed by 10 repeat grips at maximum force and repeated after 60 minutes, were lower for all those meeting ME/CFS criteria, compared with the healthy controls. Hand-grip strength parameters were also positively correlated with laboratory hemoglobin measures in both PCS groups who did and didn’t meet the Canadian ME/CFS criteria.

A total of three patients with PCS who didn’t meet ME/CFS criteria and seven with PCS who met ME/CFS criteria had sitting blood pressures of greater than 140 mm Hg systolic and/or greater than 90 mm Hg diastolic. Five patients with PCS – four who met ME/CFS criteria and one who didn’t – fulfilled criteria for postural orthostatic tachycardia syndrome. Orthostatic hypotension was diagnosed in a total of seven with PCS, including one who did not meet ME/CFS criteria and the rest who did.

Among significant laboratory findings, mannose-binding lectin deficiency, which is associated with increased infection susceptibility and found in only about 6% of historical controls, was found more frequently in both of the PCS cohorts (17% of those with ME/CFS and 23% of those without) than it has been in the past among those with ME/CFS, compared with historical controls (15%).

There was only slight elevation in C-reactive protein, the most commonly measured marker of inflammation. However, another marker indicating inflammation within the last 3-4 months, interleukin 8 assessed in erythrocytes, was above normal in 37% with PCS and ME/CFS and in 48% with PCS who did not meet the ME/CFS criteria.

Elevated antinuclear antibodies, anti–thyroid peroxidase antibodies, vitamin D deficiencies, and folic acid deficiencies were all seen in small numbers of the PCS patients. Angiotensin-converting enzyme 1 levels were below the normal range in 31% of all patients.

“We must anticipate that this pandemic has the potential to dramatically increase the number of ME/CFS patients,” Dr. Kedor and colleagues write. “At the same time, it offers the unique chance to identify ME/CFS patients in a very early stage of disease and apply interventions such as pacing and coping early with a better therapeutic prognosis. Further, it is an unprecedented opportunity to understand the underlying pathomechanism and characterize targets for specific treatment approaches.”

Dr. Scheibenbogen and Dr. Komaroff reported no relevant financial relationships.

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

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

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

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

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

COVID-19 infection is significantly associated with chronically impaired cerebral vasoreactivity (CVR), results of a small study show.

In a small prospective study, participants who previously had COVID-19, even those with mild illness, had significantly decreased CVR, compared with never-infected individuals.

Results also showed cerebral blood flow (CBF) was greater in never-infected versus previously infected participants, and whole-brain CVR was lower in previously infected versus never-infected participants. Although CVR was also smaller in those with versus those without post-COVID neurologic conditions, the difference was not considered significant.

“It is important to remember that while our findings were statistically significant, we had a relatively small sample size – 25 total participants – and so we encourage future larger studies in this domain to see if these results are reproducible at a larger scale,” lead author Andrew Callen, MD, assistant professor of radiology, Neuroradiology Section, University of Colorado at Denver, Aurora, said in an interview.

“In a practical sense, it may encourage treating clinicians to be more aggressive with preventative neurovascular and cardiovascular health measures and/or screening in this patient population,” Dr. Callen said.

The findings were published online  in the American Journal of Roentgenology.
 

Endothelial dysfunction

The acute phase SARS-CoV-2 infection “is associated with strokes that have features of both vascular inflammation and thromboembolism,” the investigators note.

Moreover, following the acute phase of infection, up to three-quarters of patients “experience persistent neurologic symptoms not attributable to another diagnosis, including headache, difficulty concentrating, vision changes, disequilibrium, and fatigue,” they write.

Preliminary studies “suggest a potential role for endothelial and circulatory dysfunction” in these symptoms, they add.

The researchers note that vessel wall imaging is an MRI technique that can detect and characterize arterial vascular inflammation and may differentiate vasculitic arterial pathology from atherosclerotic pathology.

Dr. Callen conducted previous research assessing cerebral vasoreactivity in women living with HIV. He noted that this is a population at a much higher risk of stroke, compared with uninfected individuals with otherwise similar cardiovascular risk factors, even when their viral load is controlled with antiretroviral therapies.

Evidence has pointed to chronic endothelial dysfunction in these individuals, and endothelial function and dysfunction can be measured through vasoreactivity testing, Dr. Callen said.

“As the COVID pandemic progressed, not only did we observe an increased rate of stroke in individuals acutely infected with COVID, but histopathological evidence began to emerge which suggested that the COVID-19 virus had tropism to and often damaged the vascular endothelium,” he noted.

This emerging evidence prompted Dr. Callen to wonder whether “individuals previously infected with COVID might also demonstrate long-term impairment in cerebral vasoreactivity or if we might see abnormalities using high resolution vessel wall imaging.”

In the current study, 15 individuals with prior SARS-CoV-2 infection (11 women, 4 men; mean age, 43 years) were compared with 10 never-infected individuals (8 women, 2 men; mean age, 43 years) who functioned as the control group.

The previously infected individuals, of whom three had prior critical infection and 12 had prior mild infection, were assessed, on average, about 8 months after infection. Of this group, seven had various post-COVID neurologic conditions, including headache, memory impairment, insomnia, depression, disequilibrium, fatigue, personality change, phantosmias (detecting smells that aren’t present), dysgeusia (taste disorder), and tinnitus.

All participants underwent MRI and vessel wall imaging. The MRI included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure CBF and calculate CVR. The vessel wall imaging examinations used a contrast-enhanced black-blood 3D T1-weighted sequence.
 

Imaging data

Prior to acetazolamide administration, the mean whole-cortex CBF did not differ significantly between never-infected and previously infected participants. However, following the acetazolamide administration, the mean whole-cortex CBF was greater in never-infected participants (73.8 mL/100 g/min vs. 60.5 mL/100 g/min, respectively; P = .04).

Moreover, the mean whole-brain CVR was greater in never-infected participants, compared with previously infected participants (27.8 mL/100 g/min vs. 19.1 mL/100 g/min; P < .001).

After adjusting for age and sex, researchers found that prior infection was associated with a lower whole-brain CVR (–8.9 mL/100 g/min; 95% confidence interval, 4.6-13.3 ml/100g/min; P < .001).

Previously infected individuals also showed significantly lower CVR, even after the researchers excluded those with prior critical illness.

A nonsignificant difference was found in previously infected participants, with smaller CVR in participants with versus without post-COVID neurologic symptoms (16.9 vs. 21.0 mL/100 g/min; P = .22).

In addition, 40% of the previously infected participants versus 10% of the never-infected participants had at least one vessel wall imaging abnormality – but the difference was not deemed significant (P = .18). Notably, “all detected vessel wall imaging abnormalities were morphologically consistent with atherosclerosis rather than vasculitis,” the investigators said.

Dr. Callen said it is “unknown whether the lack of statistical significance in the differences in vasoreactivity impairment with those living with long COVID symptoms is due to a lack of a biomechanistic correlation or due to statistical underpowering.”

If it is the latter, “it may emphasize the role of vascular health in those living with long COVID symptoms and potentially all individuals living with COVID,” he added.
 

Independent risk factor?

Commenting on the study for this article, Jared Narvid, MD, associate professor of neuroradiology, University of California, San Francisco, said it “adds to the literature suggesting a correlation between COVID-19 infection and measures of cerebrovascular abnormality.”

Dr. Narvid, who was not involved with the research, added that “although it is a small case-control study, it is well executed and should encourage scientists to further study whether COVID-19 infection represents an independent risk factor for cerebrovascular disease.”

The investigators agree. “Future studies are needed to determine the clinical implications arising from SARS-CoV-2–associated CVR impairment,” they write.

The study was funded by a University of Colorado department of radiology Faculty Development Seed Grant. The investigators and Dr. Narvid report no relevant financial relationships.

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

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

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

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

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

“BMI is trash. Full stop.” This controversial tweet received 26,500 likes and almost 3,000 retweets. The 400 comments from medical and non–health care personnel ranged from agreeable to contrary to offensive.

Regardless of your opinion on BMI (body mass index), this conversation highlighted that the medical community needs to discuss the limitations of BMI and decide its future.

As a Black woman who is an obesity expert living with the impact of obesity in my own life, I know the emotion that a BMI conversation can evoke. Before emotions hijack the conversation, let’s discuss BMI’s past, present, and future.
 

BMI: From observational measurement to clinical use

Imagine walking into your favorite clothing store where an eager clerk greets you with a shirt to try on. The fit is off, but the clerk insists that the shirt must fit because everyone who’s your height should be able to wear it. This scenario seems ridiculous. But this is how we’ve come to use the BMI. Instead of thinking that people of the same height may be the same size, we declare that they must be the same size.

The idea behind the BMI was conceived in 1832 by Belgian anthropologist and mathematician Adolphe Quetelet, but he didn’t intend for it to be a health measure. Instead, it was simply an observation of how people’s weight changed in proportion to height over their lifetime.

Fast-forward to the 20th century, when insurance companies began using weight as an indicator of health status. Weights were recorded in a “Life Table.” Individual health status was determined on the basis of arbitrary cut-offs for weight on the Life Tables. Furthermore, White men set the “normal” weight standards because they were the primary insurance holders.

In 1972, Dr. Ancel Keys, a physician and leading expert in body composition at the time, cried foul on this practice and sought to standardize the use of weight as a health indicator. Dr. Keys used Quetelet’s calculation and termed it the Body Mass Index.

By 1985, the U.S. National Institutes of Health and the World Health Organization adopted the BMI. By the 21st century, BMI had become widely used in clinical settings. For example, the Centers for Medicare & Medicaid Services adopted BMI as a quality-of-care measure, placing even more pressure on clinicians to use BMI as a health screening tool.
 

BMI as a tool to diagnose obesity

We can’t discuss BMI without discussing the disease of obesity. BMI is the most widely used tool to diagnose obesity. In the United States, one-third of Americans meet the criteria for obesity. Another one-third are at risk for obesity.

Compared with BMI’s relatively quick acceptance into clinical practice, however, obesity was only recently recognized as a disease.

Historically, obesity has been viewed as a lifestyle choice, fueled by misinformation and multiple forms of bias. The historical bias associated with BMI and discrimination has led some public health officials and scholars to dismiss the use of BMI or fail to recognize obesity as disease.

This is a dangerous conclusion, because it comes to the detriment of the very people disproportionately impacted by obesity-related health disparities.

Furthermore, weight bias continues to prevent people living with obesity from receiving insurance coverage for life-enhancing obesity medications and interventions.
 

Is it time to phase out BMI?

The BMI is intertwined with many forms of bias: age, gender, racial, ethnic, and even weight. Therefore, it is time to phase out BMI. However, phasing out BMI is complex and will take time, given that:

• Obesity is still a relatively “young” disease. 2023 marks the 10th anniversary of obesity’s recognition as a disease by the American Medical Association. Currently, BMI is the most widely used tool to diagnose obesity. Tools such as waist circumference, body composition, and metabolic health assessment will need to replace the BMI. Shifting from BMI emphasizes that obesity is more than a number on the scale. Obesity, as defined by the Obesity Medicine Association, is indeed a “chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences.”
• Much of our health research is tied to BMI. There have been some shifts in looking at non–weight-related health indicators. However, we need more robust studies evaluating other health indicators beyond weight and BMI. The availability of this data will help eliminate the need for BMI and promote individualized health assessment.
• Current treatment guidelines for obesity medications are based on BMI. (Note: Medications to treat obesity are called “anti-obesity” medications or AOMs. However, given the stigma associated with obesity, I prefer not to use the term “anti-obesity.”) Presently this interferes with long-term obesity treatment. Once BMI is “normal,” many patients lose insurance coverage for their obesity medication, despite needing long-term metabolic support to overcome the compensatory mechanism of weight regain. Obesity is a chronic disease that exists independent of weight status. Therefore, using non-BMI measures will help ensure appropriate lifetime support for obesity.

The preceding are barriers, not impossibilities. In the interim, if BMI is still used in any capacity, the BMI reference chart should be an adjusted BMI chart based on age, race, ethnicity, biological sex, and obesity-related conditions. Furthermore, BMI isn’t the sole determining factor of health status.

Instead, an “abnormal” BMI should initiate conversation and further testing, if needed, to determine an individual’s health. For example, compare two people of the same height with different BMIs and lifestyles. Current studies support that a person flagged as having a high adjusted BMI but practicing a healthy lifestyle and having no metabolic diseases is less at risk than a person with a “normal” BMI but high waist circumference and an unhealthy lifestyle.

Regardless of your personal feelings, the facts are clear. Technology empowers us with better tools than BMI to determine health status. Therefore, it’s not a matter of if we will stop using BMI but when.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. Connect with her at www.embraceyouweightloss.com or on Instagram @embraceyoumd. Her bestselling book, “Embrace You: Your Guide to Transforming Weight Loss Misconceptions Into Lifelong Wellness,” is Healthline.com’s Best Overall Weight Loss Book 2022 and one of Livestrong.com’s picks for the 8 Best Weight-Loss Books to Read in 2022.

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

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

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

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

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

The annual incidence of hip fractures declined in most countries from 2005 to 2018, but this rate is projected to roughly double by 2050, according to a new study of 19 countries/regions.

The study by Chor-Wing Sing, PhD, and colleagues was presented at the annual meeting of the American Society of Bone and Mineral Research. The predicted increase in hip fractures is being driven by the aging population, with the population of those age 85 and older projected to increase 4.5-fold from 2010 to 2050, they note.

The researchers also estimate that from 2018 to 2050 the incidence of fractures will increase by 1.9-fold overall – more in men (2.4-fold) than in women (1.7-fold).

In addition, rates of use of osteoporosis drugs 1 year after a hip fracture were less than 50%, with less treatment in men. Men were also more likely than women to die within 1 year of a hip fracture.

iStock/Thinkstock

Aging will fuel rise in hip fractures; more preventive treatment needed

“Even though there is a decreasing trend of hip fracture incidence in some countries, such a percentage decrease is insufficient to offset the percentage increase in the aging population,” senior co-author Ching-Lung Cheung, PhD, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, explained to this news organization.

The takeaways from the study are that “a greater effort on fracture prevention should be made to avoid the continuous increase in the number of hip fractures,” he said.

In addition, “although initiation of anti-osteoporosis medication after hip fracture is recommended in international guidelines, the 1-year treatment rate [was] well below 50% in most of the countries and regions studied. This indicates the treatment rate is far from optimal.”

“Our study also showed that the use of anti-osteoporosis medications following a hip fracture is lower in men than in women by 30% to 67%,” he said. “Thus, more attention should be paid to preventing and treating hip fractures in men.”

“The greater increase in the projected number of hip fractures in men than in women “could be [because] osteoporosis is commonly perceived as a ‘woman’s disease,’ ” he speculated.

Invited to comment, Juliet Compston, MD, who selected the study as one of the top clinical science highlight abstracts at the ASBMR meeting, agrees that “there is substantial room for improvement” in osteoporosis treatment rates following a hip fracture “in all the regions covered by the study.”

“In addition,” she continues, “the wide variations in treatment rates can provide important lessons about the most effective models of care for people who sustain a hip fracture: for example, fracture liaison services.”

Men suffer as osteoporosis perceived to be a ‘woman’s disease’

The even lower treatment rate in men than women is “concerning and likely reflects the mistaken perception that osteoporosis is predominantly a disease affecting women,” notes Dr. Compston, emeritus professor of bone medicine, University of Cambridge, United Kingdom.  

Also invited to comment, Peter R. Ebeling, MD, outgoing president of the ASBMR, said that the projected doubling of hip fractures “is likely mainly due to aging of the population, with increasing lifespan for males in particular. However, increasing urbanization and decreasing weight-bearing exercise as a result are likely to also contribute in developing countries.”

“Unfortunately, despite the advances in treatments for osteoporosis over the last 25 years, osteoporosis treatment rates remain low, and osteoporosis remains undiagnosed in postmenopausal women and older men,” added Dr. Ebeling, from Monash University, Melbourne, who was not involved with the research.

“More targeted screening for osteoporosis would help,” he said, “as would treating patients for it following other minimal trauma fractures (vertebral, distal radius, and humerus, etc.), since if left untreated, about 50% of these patients will have hip fractures later in life.”

“Some countries may be doing better because they have health quality standards for hip fracture (for example, surgery within 24 hours, investigation, and treatment for osteoporosis). In other countries like Australia, bone density tests and treatment for osteoporosis are reimbursed, increasing their uptake.”

The public health implications of this study are “substantial” according to Dr. Compston. “People who have sustained a hip fracture are at high risk of subsequent fractures if untreated. There is a range of safe, cost-effective pharmacological therapies to reduce fracture rate, and wider use of these would have a major impact on the current and future burden imposed by hip fractures in the elderly population.”

Similarly, Dr. Ebeling noted that “prevention is important to save a huge health burden for patients and costs for society.”

“Patients with minimal trauma fractures (particularly hip or spinal fractures) should be investigated and treated for osteoporosis with care pathways established in the hospitals, reaching out to the community [fracture liaison services],” he said.

Support for these is being sought under Medicare in the United States, he noted, and bone densitometry reimbursement rates also need to be higher in the United States.
 

Projections for number of hip fractures to 2050

Previous international reviews of hip fractures have been based on heterogeneous data from more than 10 to 30 years ago, the researchers note.

They performed a retrospective cohort study using a common protocol across 19 countries/regions, as described in an article about the protocol published in BMJ Open.

They analyzed data from adults aged 50 and older who were hospitalized with a hip fracture to determine 1) the annual incidence of hip fractures in 2008-2015; 2) the uptake of drugs to treat osteoporosis at 1 year after a hip fracture; and 3) all-cause mortality at 1 year after a hip fracture.

In a second step, they estimated the number of hip fractures that would occur from 2030 to 2050, using World Bank population growth projections.

The data are from 20 health care databases from 19 countries/regions: Oceania (Australia, New Zealand), Asia (Hong Kong, Japan, Singapore, South Korea, Taiwan, and Thailand), Northern Europe (Denmark, Finland, and U.K.), Western Europe (France, Germany, Italy, The Netherlands, and Spain), and North and South America (Canada, United States, and Brazil).

The population in Japan was under age 75. U.S. data are from two databases: Medicare (age ≥ 65) and Optum.

Most databases (13) covered 90%-100% of the national population, and the rest covered 5%-70% of the population.

From 2008 to 2015, the annual incidence of hip fractures declined in 11 countries/regions (Singapore, Denmark, Hong Kong, Taiwan, Finland, U.K., Italy, Spain, United States [Medicare], Canada, and New Zealand).

“One potential reason that some countries have seen relatively large declines in hip fractures is better osteoporosis management and post-fracture care,” said Dr. Sing in a press release issued by ASBMR. “Better fall-prevention programs and clearer guidelines for clinical care have likely made a difference.”

Hip fracture incidence increased in five countries (The Netherlands, South Korea, France, Germany, and Brazil) and was stable in four countries (Australia, Japan, Thailand, and United States [Optum]).

The United Kingdom had the highest rate of osteoporosis treatment at 1-year after a hip fracture (50.3%). Rates in the other countries/regions ranged from 11.5% to 37%.

Fewer men than women were receiving drugs for osteoporosis at 1 year (range 5.1% to 38.2% versus 15.0% to 54.7%).

From 2005 to 2018, rates of osteoporosis treatment at 1 year after a hip fracture declined in six countries, increased in four countries, and were stable in five countries.

All-cause mortality within 1 year of hip fracture was higher in men than in women (range 19.2% to 35.8% versus 12.1% to 25.4%).

“Among the studied countries and regions, the U.S. ranks fifth with the highest hip fracture incidence,” Dr. Cheung replied when specifically asked about this. “The risk of hip fracture is determined by multiple factors: for example, lifestyle, diet, genetics, as well as management of osteoporosis,” he noted.

“Denmark is the only country showing no projected increase, and it is because Denmark had a continuous and remarkable decrease in the incidence of hip fractures,” he added, which “can offset the number of hip fractures contributed by the population aging.”

The study was funded by Amgen. Dr. Sing and Dr. Cheung have reported no relevant financial relationships. One of the study authors is employed by Amgen.

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

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

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

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

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

New York Governor Kathy Hochul declared a state disaster emergency on Sept. 9 after the polio virus has been detected in another county. The order allows EMS workers, midwives, and pharmacists to administer the vaccine and permits physicians and nurse practitioners to issue standing orders for polio vaccines.

“On polio, we simply cannot roll the dice,” New York State Health Commissioner Dr. Mary T. Bassett said in a news release. “If you or your child are unvaccinated or not up to date with vaccinations, the risk of paralytic disease is real. I urge New Yorkers to not accept any risk at all.”

In July, an unvaccinated adult man in Rockland County, which is north of New York City, was diagnosed with polio virus. It was the first confirmed case of the virus in the United States since 2013.

New York state health officials have not announced any additional polio cases. Since as early as April, polio has also been detected in wastewater samples in New York City and in Rockland, Orange, and Sullivan counties. In August, the virus was detected in wastewater from Nassau County on Long Island.

New York’s statewide polio vaccination rate is 79%, and the New York State Department of Health is aiming for a rate over 90%, the announcement said. In some counties, vaccination rates are far below the state average, including Rockland County (60%), Orange County (59%), and Sullivan County (62%). Nassau County’s polio vaccination rate is similar to the state average.

“Polio immunization is safe and effective – protecting nearly all people against disease who receive the recommended doses,” Dr. Basset said; “Do not wait to vaccinate.”

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

Those with risk factors associated with COVID-19–related death post coronavirus vaccination should be considered a priority for COVID therapeutics and further booster doses say U.K. researchers.

The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.

For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
 

Prioritization of booster doses and COVID-19 treatments

The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”

During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).

They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.

Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
 

Dementia concern

With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”

Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.

In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.

David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”

The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.

However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.

“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.

A version of this article first appeared on Medscape UK.

Those with risk factors associated with COVID-19–related death post coronavirus vaccination should be considered a priority for COVID therapeutics and further booster doses say U.K. researchers.

The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.

For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
 

Prioritization of booster doses and COVID-19 treatments

The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”

During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).

They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.

Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
 

Dementia concern

With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”

Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.

In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.

David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”

The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.

However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.

“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.

A version of this article first appeared on Medscape UK.

Those with risk factors associated with COVID-19–related death post coronavirus vaccination should be considered a priority for COVID therapeutics and further booster doses say U.K. researchers.

The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.

For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
 

Prioritization of booster doses and COVID-19 treatments

The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”

During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).

They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.

Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
 

Dementia concern

With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”

Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.

In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.

David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”

The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.

However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.

“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.

A version of this article first appeared on Medscape UK.

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

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

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

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

New research shows that “polypills” can prevent a combination of cardiovascular events and cardiovascular deaths among patients who have recently experienced a myocardial infarction.

But results from the SECURE trial, published in the New England Journal of Medicine, also raise questions.

How do the polypills reduce cardiovascular problems? And will they ever be available in the United States?

Questions about how they work center on a mystery in the trial data: the polypill – containing aspirin, an angiotensin-converting enzyme (ACE) inhibitor, and a statin – apparently conferred substantial cardiovascular protection while producing average blood pressure and lipid levels that were virtually the same as with usual care.

As to when polypills will be available, the answer may hinge on whether companies, government agencies, or philanthropic foundations come to see making and paying for such treatments – combinations of typically inexpensive generic drugs in a single pill for the sake of convenience and greater adherence – as financially worthwhile.
 

A matter of adherence?

In the SECURE trial, presented late August at the annual congress of the European Society of Cardiology, Barcelona, investigators randomly assigned 2,499 patients with an MI in the previous 6 months to receive usual care or a polypill.

Patients in the usual-care group typically received the same types of treatments included the polypill, only taken separately. Different versions of the polypill were available to allow for titration to tolerated doses of the component medications: aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 mg or 40 mg).

Researchers used the Morisky Medication Adherence Scale to gauge participants’ adherence to their medication regimen and found the polypill group was more adherent. Patients who received the polypill were more likely to have a high level of adherence at 6 months (70.6% vs. 62.7%) and 24 months (74.1% vs. 63.2%), they reported. (The Morisky tool is the subject of some controversy because of aggressive licensing tactics of its creator.)

The primary endpoint of cardiovascular death, MI, stroke, or urgent revascularization was significantly less likely in the polypill group during a median of 3 years of follow-up (hazard ratio, 0.76; P = .02).

“A primary-outcome event occurred in 118 of 1,237 patients (9.5%) in the polypill group and in 156 of 1,229 (12.7%) in the usual-care group,” the researchers report.

“Probably, adherence is the most important reason of how this works,” Valentin Fuster, MD, physician-in-chief at Mount Sinai Hospital, New York, who led the study, said at ESC 2022.

Still, some clinicians were left scratching their heads by the lack of difference between treatment groups in average blood pressure and levels of low-density lipoprotein (LDL) cholesterol.

In the group that received the polypill, average systolic and diastolic blood pressure at 24 months were 135.2 mmHg and 74.8 mmHg, respectively. In the group that received usual care, those values were 135.5 mmHg and 74.9 mmHg, respectively.

Likewise, “no substantial differences were found in LDL-cholesterol levels over time between the groups, with a mean value at 24 months of 67.7 mg/dL in the polypill group and 67.2 mg/dL in the usual-care group,” according to the researchers.

One explanation for the findings is that greater adherence led to beneficial effects that were not reflected in lipid and blood pressure measurements, the investigators said. Alternatively, the open-label trial design could have led to different health behaviors between groups, they suggested.

Martha Gulati, MD, director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles, said she loves the idea of polypills. But she wonders about the lack of difference in blood pressure and lipids in SECURE.

Dr. Gulati said she sees in practice how medication adherence and measurements of blood pressure and lipids typically go hand in hand.

When a patient initially responds to a medication, but then their LDL cholesterol goes up later, “my first question is, ‘Are you still taking your medication or how frequently are you taking it?’” Dr. Gulati said in an interview. “And I get all kinds of answers.”

“If you are more adherent, why wouldn’t your LDL actually be lower, and why wouldn’t your blood pressure be lower?” she asked.
 

Can the results be replicated?

Ethan J. Weiss, MD, a cardiologist and volunteer associate clinical professor of medicine at the University of California, San Francisco, said the SECURE results are “spectacular,” but the seeming disconnect with the biomarker measurements “doesn’t make for a clean story.”

“It just seems like if you are making an argument that this is a way to improve compliance ... you would see some evidence of improved compliance objectively” in the biomarker readings, Dr. Weiss said.

Trying to understand how the polypill worked requires more imagination. “Or it makes you just say, ‘Who cares what the mechanism is?’ These people did a lot better, full stop, and that’s all that matters,” he said.

Dr. Weiss said he expects some degree of replication of the results may be needed before practice changes.

To Steven E. Nissen, MD, chief academic officer of the Heart and Vascular Institute at Cleveland Clinic, the results “don’t make any sense.”

“If they got the same results on the biomarkers that the pill was designed to intervene upon, why are the [primary outcome] results different? It’s completely unexplained,” Dr. Nissen said.

In general, Dr. Nissen has not been an advocate of the polypill approach in higher-income countries.

“Medicine is all about customization of therapy,” he said. “Not everybody needs blood pressure lowering. Not everybody needs the same intensity of LDL reduction. We spend much of our lives seeing patients and treating their blood pressure, and if it doesn’t come down adequately, giving them a higher dose or adding another agent.”

Polypills might be reasonable for primary prevention in countries where people have less access to health care resources, he added. In such settings, a low-cost, simple treatment strategy might have benefit.

But Dr. Nissen still doesn’t see a role for a polypill in secondary prevention.

“I think we have to take a step back, take a deep breath, and look very carefully at the science and try to understand whether this, in fact, is sensible,” he said. “We may need another study to see if this can be replicated.”

For Dhruv S. Kazi, MD, the results of the SECURE trial offer an opportunity to rekindle conversations about the use of polypills for cardiovascular protection. These conversations and studies have been taking place for nearly two decades.

Dr. Kazi, associate director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center, Boston, has used models to study the expected cost-effectiveness of polypills in various countries.

Although polypills can improve patients’ adherence to their prescribed medications, Dr. Kazi and colleagues have found that treatment gaps are “often at the physician level,” with many patients not prescribed all of the medications from which they could benefit.

Availability of polypills could help address those gaps. At the same time, many patients, even those with higher incomes, may have a strong preference for taking a single pill.

Dr. Kazi’s research also shows that a polypill approach may be more economically attractive as countries develop because successful treatment averts cardiovascular events that are costlier to treat.

“In the United States, in order for this to work, we would need a polypill that is both available widely but also affordable,” Dr. Kazi said. “It is going to require a visionary mover” to make that happen.

That could include philanthropic foundations. But it could also be a business opportunity for a company like Barcelona-based Ferrer, which provided the polypills for the SECURE trial.

The clinical and economic evidence in support of polypills has been compelling, Dr. Kazi said: “We have to get on with the business of implementing something that is effective and has the potential to greatly improve population health at scale.” 

The SECURE trial was funded by the European Union Horizon 2020 program and coordinated by the Spanish National Center for Cardiovascular Research (CNIC). Ferrer International provided the polypill that was used in the trial. CNIC receives royalties for sales of the polypill from Ferrer. Dr. Weiss is starting a biotech company unrelated to this area of research.

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

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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

Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, has been approved by the Food and Drug Administration for treating adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy, the manufacturer announced on Sept. 9.

Deucravacitinib targets TYK2, which inhibits signaling of interleukin-23, interleukin-12, and type 1 interferons, key cytokines involved in the pathogenesis of multiple immune-mediated diseases, according to Bristol Myers Squibb (BMS). This is the first approval for deucravacitinib, which will be marketed as Sotyktu, and the first drug in this class to be approved.

It is also currently under review for the same indication in Europe and Japan, and elsewhere, and for treating pustular psoriasis and erythrodermic psoriasis in Japan.

FDA approval was based on the results of POETYK PSO-1 and POETYK PSO-2, phase 3 trials of almost 1,700 adults with moderate to severe plaque psoriasis. In these studies, treatment with once-daily deucravacitinib showed significant and clinically meaningful improvements in skin clearance and symptoms, compared with placebo and with apremilast (Otezla), according to the company.

In the two studies, patients were randomly assigned to receive 6 mg daily of deucravacitinib, placebo, or a 30-mg twice-daily dose of apremilast, the oral phosphodiesterase 4 inhibitor approved for psoriasis. The primary endpoints were the percentage of patients who achieved a Psoriasis Area and Severity Index (PASI) 75 response and a static Physician’s Global Assessment (sPGA) score of 0 or 1 (clear or almost clear) at 16 weeks.

At 16 weeks, 58% and 53% of patients receiving deucravacitinib in the POETYK PSO-1 and POETYK PSO-2 studies, respectively, achieved PASI 75 response, compared with 13% and 9% of those receiving placebo (P < .0001 for both) and 35% and 40% receiving apremilast (P < .0001, P = .0004, respectively), according to the company’s announcement of the approval. PASI 75 responses were maintained through 52 weeks among the patients who remained on treatment, in both studies, according to BMS.

In the POETYK PSO-1 and PSO-2 studies, respectively, 54% and 50% of those on deucravacitinib achieved an sPGA of 0/1 at 16 weeks, compared with 7% and 9% of those receiving placebo (P < .0001 for both) and 32% and 34% of those receiving apremilast (P < .0001 for both).

Across the two studies, at 16 weeks, the most common adverse events that affected at least 1% of patients on deucravacitinib and that occurred at higher rates than in the placebo group were upper respiratory infections (19.2%), increases in serum creatine phosphokinase (2.7%), herpes simplex (2%), mouth ulcers (1.9%), folliculitis (1.7%), and acne (1.4%). Adverse events resulting in discontinuation of treatment were reported in 2.4% of persons receiving deucravacitinib and 5.2% of those receiving apremilast, compared with 3.8% of those receiving placebo.

Up to 16 weeks, according to the BMS statement, 28% of persons receiving deucravacitinib had infections, most of which were mild to moderate and not serious and did not result in stopping treatment, compared with 22% of those receiving placebo. In addition, five patients treated with deucravacitinib and five patients receiving placebo had serious infections, and three patients receiving deucravacitinib had cancer (not including nonmelanoma skin cancer).

Deucravacitinib is also being evaluated in clinical trials for psoriatic arthritis, lupus, and inflammatory bowel disease. It is not recommended for use in combination with other potent immunosuppressants, according to BMS.

The prescribing information and patient medication guide are available online.

The POETYK PSO-1 and POETYK PSO-2 studies were funded by Bristol Myers Squibb.

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