Clinician Reviews

More than 3 years into the COVID-19 era, most Americans have settled back into their prepandemic lifestyles. But a new dominant variant and rising hospitalization numbers may give way to another summer surge.

Since April, a new COVID variant has cropped up. According to recent Centers for Disease Control and Prevention data, EG.5 – from the Omicron family – now makes up 17% of all cases in the United States, up from 7.5% in the first week of July. 

A summary from the Center for Infectious Disease Research and Policy at the University of Minnesota says that EG.5, nicknamed “Eris” by health trackers, is nearly the same as its parent strain, XBB.1.9.2, but has one extra spike mutation. 

Along with the news of EG.5’s growing prevalence, COVID-related hospitalization rates have increased by 12.5% during the week ending on July 29 – the most significant uptick since December. Still, no connection has been made between the new variant and rising hospital admissions. And so far, experts have found no difference in the severity of illness or symptoms between Eris and the strains that came before it.
 

Cause for concern?

The COVID virus has a great tendency to mutate, said William Schaffner, MD, a professor of infectious diseases at Vanderbilt University, Nashville, Tenn. 

“Fortunately, these are relatively minor mutations.” Even so, SARS-CoV-2, the virus that causes COVID-19, continues to be highly contagious. “There isn’t any doubt that it’s spreading – but it’s not more serious.”

So, Dr. Schaffner doesn’t think it’s time to panic. He prefers calling it an “uptick” in cases instead of a “surge,” because a surge “sounds too big.”

While the numbers are still low, compared with 2022’s summer surge, experts still urge people to stay aware of changes in the virus. “I do not think that there is any cause for alarm,” agreed Bernard Camins, MD, an infectious disease specialist at Mount Sinai Hospital, New York.

So why the higher number of cases? “There has been an increase in COVID cases this summer, probably related to travel, socializing, and dwindling masking,” said Anne Liu, MD, an allergy, immunology, and infectious disease specialist at Stanford (Calif.) University. Even so, “because of an existing level of immunity from vaccination and prior infections, it has been limited and case severity has been lower than in prior surges.”
 

What the official numbers say

The CDC no longer updates its COVID Data Tracker Weekly Review. They stopped in May 2023 when the federal public health emergency ended.

But the agency continues to track COVID-19 cases, hospitalizations, ED visits, and deaths in different ways. The key takeaways include 9,056 new hospitalizations reported for the week ending July 29, 2023. That is relatively low, compared with July 30, 2022, when the weekly new hospitalization numbers topped 44,000. 

“Last year, we saw a summer wave with cases peaking around mid-July. In that sense, our summer wave is coming a bit later than last year,” said Pavitra Roychoudhury, PhD, an assistant professor and researcher in the vaccine and infectious disease division at the University of Washington, Seattle. 

“It’s unclear how high the peak will be during this current wave. Levels of SARS-CoV-2 in wastewater, as well as the number of hospitalizations, are currently lower than this time last year.” 

For part of the pandemic, the CDC recommended people monitor COVID numbers in their own communities. But the agency’s local guidance on COVID is tied to hospital admission levels, which are currently low for more than 99% of the country, even if they are increasing. 

So, while it’s good news that hospitalization numbers are smaller, it means the agency’s ability to identify local outbreaks or hot spots of SARS-CoV-2 is now more limited. 

It’s not just an uptick in hospitalizations nationwide, as other COVID-19 indicators, including ED visits, positive tests, and wastewater levels, are increasing across the United States. 

In terms of other metrics: 

• On June 19, 0.47% of ED visits resulted in a positive COVID diagnosis. On Aug. 4, that rate had more than doubled to 1.1%. 
• On July 29, 8.9% of people who took a COVID test reported a positive result. The positivity rate has been increasing since June 10, when 4.1% of tests came back positive. This figure only includes test results reported to the CDC. Results of home testing remain largely unknown. 
• The weekly percentage of deaths related to COVID-19 was 1% as of July 29. That’s low, compared with previous rates. For example, for the week ending July 30, 2022, it was 5.8%.

What about new COVID vaccines?

As long as the general public continue to make informed decisions and get the new Omicron vaccine or booster once it’s available, experts predict lower hospitalization rates this winter. 

“Everyone should get the Omicron booster when it becomes available,” recommended Dean Winslow, MD, a professor of medicine at Stanford University. 

In the meantime, “it is important to emphasize that COVID-19 is going to be with us for the foreseeable future,” he said. Since the symptoms linked to these newer Omicron subvariants are generally milder than with earlier variants, “if one has even mild cold symptoms, it is a good idea to test yourself for COVID-19 and start treatment early if one is elderly or otherwise at high risk for severe disease.”

Dr. Schaffner remains optimistic for now. “We anticipate that the vaccines we currently have available, and certainly the vaccine that is being developed for this fall, will continue to prevent severe disease associated with this virus.”

Although it’s difficult to predict an exact time line, Dr. Schaffner said they could be available by the end of September. 

His predictions assume “that we don’t have a new nasty variant that crops up somewhere in the world,” he said. “[If] things continue to move the way they have been, we anticipate that this vaccine ... will be really effective and help us keep out of the hospital during this winter, when we expect more of an increase of COVID once again.” 

Asked for his outlook on vaccine recommendations, Dr. Camins was less certain. “It is too soon to tell.” Guidance on COVID shots will be based on results of ongoing studies. “It would be prudent, however, for everyone to plan on getting the flu shot in September.”

Stay alert and stay realistic

Cautious optimism and a call to remain vigilant seem like the consensus at the moment. While the numbers remain low so far and the uptick in new cases and hospitalizations are relatively small, compared with past scenarios, “it makes sense to boost our anti-Omicron antibody levels with immunizations before fall and winter,” Dr. Liu said. 

“It’s just advisable for everyone – especially those who are at higher risk for hospitalization or death – to be aware,” Dr. Camins said, “so they can form their own decisions to participate in activities that may put them at risk for contracting COVID-19.”

While respiratory virus work best at keeping people with the flu, COVID, or RSV out of the hospital, they’re not as good at preventing milder infections. Dr. Schaffner said: “If we don’t expect perfection, we won’t be so disappointed.”

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

More than 3 years into the COVID-19 era, most Americans have settled back into their prepandemic lifestyles. But a new dominant variant and rising hospitalization numbers may give way to another summer surge.

Since April, a new COVID variant has cropped up. According to recent Centers for Disease Control and Prevention data, EG.5 – from the Omicron family – now makes up 17% of all cases in the United States, up from 7.5% in the first week of July. 

A summary from the Center for Infectious Disease Research and Policy at the University of Minnesota says that EG.5, nicknamed “Eris” by health trackers, is nearly the same as its parent strain, XBB.1.9.2, but has one extra spike mutation. 

Along with the news of EG.5’s growing prevalence, COVID-related hospitalization rates have increased by 12.5% during the week ending on July 29 – the most significant uptick since December. Still, no connection has been made between the new variant and rising hospital admissions. And so far, experts have found no difference in the severity of illness or symptoms between Eris and the strains that came before it.
 

Cause for concern?

The COVID virus has a great tendency to mutate, said William Schaffner, MD, a professor of infectious diseases at Vanderbilt University, Nashville, Tenn. 

“Fortunately, these are relatively minor mutations.” Even so, SARS-CoV-2, the virus that causes COVID-19, continues to be highly contagious. “There isn’t any doubt that it’s spreading – but it’s not more serious.”

So, Dr. Schaffner doesn’t think it’s time to panic. He prefers calling it an “uptick” in cases instead of a “surge,” because a surge “sounds too big.”

While the numbers are still low, compared with 2022’s summer surge, experts still urge people to stay aware of changes in the virus. “I do not think that there is any cause for alarm,” agreed Bernard Camins, MD, an infectious disease specialist at Mount Sinai Hospital, New York.

So why the higher number of cases? “There has been an increase in COVID cases this summer, probably related to travel, socializing, and dwindling masking,” said Anne Liu, MD, an allergy, immunology, and infectious disease specialist at Stanford (Calif.) University. Even so, “because of an existing level of immunity from vaccination and prior infections, it has been limited and case severity has been lower than in prior surges.”
 

What the official numbers say

The CDC no longer updates its COVID Data Tracker Weekly Review. They stopped in May 2023 when the federal public health emergency ended.

But the agency continues to track COVID-19 cases, hospitalizations, ED visits, and deaths in different ways. The key takeaways include 9,056 new hospitalizations reported for the week ending July 29, 2023. That is relatively low, compared with July 30, 2022, when the weekly new hospitalization numbers topped 44,000. 

“Last year, we saw a summer wave with cases peaking around mid-July. In that sense, our summer wave is coming a bit later than last year,” said Pavitra Roychoudhury, PhD, an assistant professor and researcher in the vaccine and infectious disease division at the University of Washington, Seattle. 

“It’s unclear how high the peak will be during this current wave. Levels of SARS-CoV-2 in wastewater, as well as the number of hospitalizations, are currently lower than this time last year.” 

For part of the pandemic, the CDC recommended people monitor COVID numbers in their own communities. But the agency’s local guidance on COVID is tied to hospital admission levels, which are currently low for more than 99% of the country, even if they are increasing. 

So, while it’s good news that hospitalization numbers are smaller, it means the agency’s ability to identify local outbreaks or hot spots of SARS-CoV-2 is now more limited. 

It’s not just an uptick in hospitalizations nationwide, as other COVID-19 indicators, including ED visits, positive tests, and wastewater levels, are increasing across the United States. 

In terms of other metrics: 

• On June 19, 0.47% of ED visits resulted in a positive COVID diagnosis. On Aug. 4, that rate had more than doubled to 1.1%. 
• On July 29, 8.9% of people who took a COVID test reported a positive result. The positivity rate has been increasing since June 10, when 4.1% of tests came back positive. This figure only includes test results reported to the CDC. Results of home testing remain largely unknown. 
• The weekly percentage of deaths related to COVID-19 was 1% as of July 29. That’s low, compared with previous rates. For example, for the week ending July 30, 2022, it was 5.8%.

What about new COVID vaccines?

As long as the general public continue to make informed decisions and get the new Omicron vaccine or booster once it’s available, experts predict lower hospitalization rates this winter. 

“Everyone should get the Omicron booster when it becomes available,” recommended Dean Winslow, MD, a professor of medicine at Stanford University. 

In the meantime, “it is important to emphasize that COVID-19 is going to be with us for the foreseeable future,” he said. Since the symptoms linked to these newer Omicron subvariants are generally milder than with earlier variants, “if one has even mild cold symptoms, it is a good idea to test yourself for COVID-19 and start treatment early if one is elderly or otherwise at high risk for severe disease.”

Dr. Schaffner remains optimistic for now. “We anticipate that the vaccines we currently have available, and certainly the vaccine that is being developed for this fall, will continue to prevent severe disease associated with this virus.”

Although it’s difficult to predict an exact time line, Dr. Schaffner said they could be available by the end of September. 

His predictions assume “that we don’t have a new nasty variant that crops up somewhere in the world,” he said. “[If] things continue to move the way they have been, we anticipate that this vaccine ... will be really effective and help us keep out of the hospital during this winter, when we expect more of an increase of COVID once again.” 

Asked for his outlook on vaccine recommendations, Dr. Camins was less certain. “It is too soon to tell.” Guidance on COVID shots will be based on results of ongoing studies. “It would be prudent, however, for everyone to plan on getting the flu shot in September.”

Stay alert and stay realistic

Cautious optimism and a call to remain vigilant seem like the consensus at the moment. While the numbers remain low so far and the uptick in new cases and hospitalizations are relatively small, compared with past scenarios, “it makes sense to boost our anti-Omicron antibody levels with immunizations before fall and winter,” Dr. Liu said. 

“It’s just advisable for everyone – especially those who are at higher risk for hospitalization or death – to be aware,” Dr. Camins said, “so they can form their own decisions to participate in activities that may put them at risk for contracting COVID-19.”

While respiratory virus work best at keeping people with the flu, COVID, or RSV out of the hospital, they’re not as good at preventing milder infections. Dr. Schaffner said: “If we don’t expect perfection, we won’t be so disappointed.”

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

More than 3 years into the COVID-19 era, most Americans have settled back into their prepandemic lifestyles. But a new dominant variant and rising hospitalization numbers may give way to another summer surge.

Since April, a new COVID variant has cropped up. According to recent Centers for Disease Control and Prevention data, EG.5 – from the Omicron family – now makes up 17% of all cases in the United States, up from 7.5% in the first week of July. 

A summary from the Center for Infectious Disease Research and Policy at the University of Minnesota says that EG.5, nicknamed “Eris” by health trackers, is nearly the same as its parent strain, XBB.1.9.2, but has one extra spike mutation. 

Along with the news of EG.5’s growing prevalence, COVID-related hospitalization rates have increased by 12.5% during the week ending on July 29 – the most significant uptick since December. Still, no connection has been made between the new variant and rising hospital admissions. And so far, experts have found no difference in the severity of illness or symptoms between Eris and the strains that came before it.
 

Cause for concern?

The COVID virus has a great tendency to mutate, said William Schaffner, MD, a professor of infectious diseases at Vanderbilt University, Nashville, Tenn. 

“Fortunately, these are relatively minor mutations.” Even so, SARS-CoV-2, the virus that causes COVID-19, continues to be highly contagious. “There isn’t any doubt that it’s spreading – but it’s not more serious.”

So, Dr. Schaffner doesn’t think it’s time to panic. He prefers calling it an “uptick” in cases instead of a “surge,” because a surge “sounds too big.”

While the numbers are still low, compared with 2022’s summer surge, experts still urge people to stay aware of changes in the virus. “I do not think that there is any cause for alarm,” agreed Bernard Camins, MD, an infectious disease specialist at Mount Sinai Hospital, New York.

So why the higher number of cases? “There has been an increase in COVID cases this summer, probably related to travel, socializing, and dwindling masking,” said Anne Liu, MD, an allergy, immunology, and infectious disease specialist at Stanford (Calif.) University. Even so, “because of an existing level of immunity from vaccination and prior infections, it has been limited and case severity has been lower than in prior surges.”
 

What the official numbers say

The CDC no longer updates its COVID Data Tracker Weekly Review. They stopped in May 2023 when the federal public health emergency ended.

But the agency continues to track COVID-19 cases, hospitalizations, ED visits, and deaths in different ways. The key takeaways include 9,056 new hospitalizations reported for the week ending July 29, 2023. That is relatively low, compared with July 30, 2022, when the weekly new hospitalization numbers topped 44,000. 

“Last year, we saw a summer wave with cases peaking around mid-July. In that sense, our summer wave is coming a bit later than last year,” said Pavitra Roychoudhury, PhD, an assistant professor and researcher in the vaccine and infectious disease division at the University of Washington, Seattle. 

“It’s unclear how high the peak will be during this current wave. Levels of SARS-CoV-2 in wastewater, as well as the number of hospitalizations, are currently lower than this time last year.” 

For part of the pandemic, the CDC recommended people monitor COVID numbers in their own communities. But the agency’s local guidance on COVID is tied to hospital admission levels, which are currently low for more than 99% of the country, even if they are increasing. 

So, while it’s good news that hospitalization numbers are smaller, it means the agency’s ability to identify local outbreaks or hot spots of SARS-CoV-2 is now more limited. 

It’s not just an uptick in hospitalizations nationwide, as other COVID-19 indicators, including ED visits, positive tests, and wastewater levels, are increasing across the United States. 

In terms of other metrics: 

• On June 19, 0.47% of ED visits resulted in a positive COVID diagnosis. On Aug. 4, that rate had more than doubled to 1.1%. 
• On July 29, 8.9% of people who took a COVID test reported a positive result. The positivity rate has been increasing since June 10, when 4.1% of tests came back positive. This figure only includes test results reported to the CDC. Results of home testing remain largely unknown. 
• The weekly percentage of deaths related to COVID-19 was 1% as of July 29. That’s low, compared with previous rates. For example, for the week ending July 30, 2022, it was 5.8%.

What about new COVID vaccines?

As long as the general public continue to make informed decisions and get the new Omicron vaccine or booster once it’s available, experts predict lower hospitalization rates this winter. 

“Everyone should get the Omicron booster when it becomes available,” recommended Dean Winslow, MD, a professor of medicine at Stanford University. 

In the meantime, “it is important to emphasize that COVID-19 is going to be with us for the foreseeable future,” he said. Since the symptoms linked to these newer Omicron subvariants are generally milder than with earlier variants, “if one has even mild cold symptoms, it is a good idea to test yourself for COVID-19 and start treatment early if one is elderly or otherwise at high risk for severe disease.”

Dr. Schaffner remains optimistic for now. “We anticipate that the vaccines we currently have available, and certainly the vaccine that is being developed for this fall, will continue to prevent severe disease associated with this virus.”

Although it’s difficult to predict an exact time line, Dr. Schaffner said they could be available by the end of September. 

His predictions assume “that we don’t have a new nasty variant that crops up somewhere in the world,” he said. “[If] things continue to move the way they have been, we anticipate that this vaccine ... will be really effective and help us keep out of the hospital during this winter, when we expect more of an increase of COVID once again.” 

Asked for his outlook on vaccine recommendations, Dr. Camins was less certain. “It is too soon to tell.” Guidance on COVID shots will be based on results of ongoing studies. “It would be prudent, however, for everyone to plan on getting the flu shot in September.”

Stay alert and stay realistic

Cautious optimism and a call to remain vigilant seem like the consensus at the moment. While the numbers remain low so far and the uptick in new cases and hospitalizations are relatively small, compared with past scenarios, “it makes sense to boost our anti-Omicron antibody levels with immunizations before fall and winter,” Dr. Liu said. 

“It’s just advisable for everyone – especially those who are at higher risk for hospitalization or death – to be aware,” Dr. Camins said, “so they can form their own decisions to participate in activities that may put them at risk for contracting COVID-19.”

While respiratory virus work best at keeping people with the flu, COVID, or RSV out of the hospital, they’re not as good at preventing milder infections. Dr. Schaffner said: “If we don’t expect perfection, we won’t be so disappointed.”

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

A new predictive tool known as the Psoriatic Arthritis Risk Estimation Tool (PRESTO) is now available to help clinicians estimate the risk of psoriatic arthritis (PsA) in their patients with psoriasis.

Though it requires further validation, researchers led by rheumatologist Lihi Eder, MD, PhD, of the Women’s College Research Institute at Women’s College Hospital, Toronto, characterized the development and validation of PRESTO as “an important first step in the development and testing of interventional strategies that may ultimately halt disease progression,” they wrote in their study of the tool, which published in Arthritis & Rheumatology. Dr. Eder presented a summary of progress on the effort at the 2023 annual meeting of the Canadian Rheumatology Association.

To develop and validate the tool, the researchers evaluated 635 patients from the University of Toronto Psoriasis Cohort, which was launched in 2006 as a prospective longitudinal cohort study to examine risk factors for the development of PsA among patients with psoriasis. Patients enrolled in the cohort have a dermatologist-confirmed diagnosis of psoriasis and are assessed by a rheumatologist prior to enrollment to exclude those with inflammatory arthritis in the past or at the time of assessment.

To develop prediction models for PsA, Dr. Eder and colleagues used information from the patient cohort demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms. Next, they used multivariable logistic regression models adjusting for covariates, duration of psoriasis, and the log duration at risk to estimate the probability of developing PsA within 1-year and 5-year time windows from consecutive study visits.

The mean age of the study participants was 47 years, 76% were White, and 57% were male; and they had psoriasis for a mean of 16 years. The researchers found that 51 patients developed PsA during the 1-year follow-up, and 71 developed PsA during the 5-year follow-up. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (area under the curve, 72.3).

In addition, the risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesions, psoriasis severity, fatigue, pain, and use of systemic non-biologic medication or phototherapy (AUC, 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities.

“Interestingly, several previously reported risk factors for PsA, such as HLA-B27, family history of PsA, uveitis, and flexural psoriasis, were not included in the risk prediction model due to their scarcity in our cohort,” the researchers wrote. “This finding may be due to immortal time bias which can complicate the development of risk prediction models for PsA. Genetic factors or their surrogates (e.g., family history of PsA) are associated with the development of PsA concurrently or shortly after the onset of psoriasis.”

They acknowledged certain limitations of the study, including its relatively small sample size and questionable generalizability of the study findings, “as most of the patients were recruited from dermatology clinics leading to overrepresentation of moderate-severe psoriasis. Therefore, PRESTO will require an external validation to assess its performance in other populations of psoriasis patients with different characteristics.”

Saakshi Khattri, MD, a board-certified dermatologist, rheumatologist, and internist at the Icahn School of Medicine at Mount Sinai, New York, who was not involved in the study and was asked to comment on the results, characterized the PRESTO tool as “an interesting step in the right direction, but it’s the first step.”

courtesy Dr. Saakshi Khattri

Since dermatologists are usually the first point of contact for psoriasis patients, she added, “a risk calculator can be helpful, but the question remains: When do we refer them to a rheumatologist? If the risk comes to 5%, is that a low risk that doesn’t need referral to rheumatology? I don’t think those questions have been answered here. From a rheumatology perspective, does the risk calculator help me decide when to intervene? At present, I’m not sure it does. Perhaps a higher score might make us intervene sooner if our clinical exam doesn’t show swollen or tender joints.”

Clinical exam findings and history she considers as a rheumatologist before making treatment recommendations include the following: Are there swollen and tender joints? Does the patient report morning stiffness for upwards of 30 minutes? Do they have enthesitis or dactylitis? Is there axial involvement? “Imaging can help if there isn’t anything on clinical exam and the history is compelling and/or the patient has risk factors for PsA,” she said.

The study’s finding of biologic use being associated with risk of developing PsA at year 1 but not at year 5 is “confusing,” Dr. Khattri added. “My concern is, will that now dissuade our moderate to severe psoriasis patients from using biologics to clear their psoriasis? We know that biologics are indicated for moderate to severe psoriasis. We also know psoriasis is associated with increased cardiovascular risk and there’s data to suggest that treatment with biologics with its resultant decrease in systemic inflammation can decrease cardiovascular risk.”

The study was supported by a New Investigator Grant from the Physician Services Incorporated Foundation. Dr. Eder disclosed that she is supported by the Canada Research Chair in Inflammatory Rheumatic Diseases. Dr. Khattri reported that she is a member of the advisory board for UCB, Janssen, AbbVie, Regeneron, Sanofi, Lilly, Argenx, and Arcutis. She has also received research funds from Incyte, AbbVie, Leo, Galderma, Pfizer, and Acelyrin.

A new predictive tool known as the Psoriatic Arthritis Risk Estimation Tool (PRESTO) is now available to help clinicians estimate the risk of psoriatic arthritis (PsA) in their patients with psoriasis.

Though it requires further validation, researchers led by rheumatologist Lihi Eder, MD, PhD, of the Women’s College Research Institute at Women’s College Hospital, Toronto, characterized the development and validation of PRESTO as “an important first step in the development and testing of interventional strategies that may ultimately halt disease progression,” they wrote in their study of the tool, which published in Arthritis & Rheumatology. Dr. Eder presented a summary of progress on the effort at the 2023 annual meeting of the Canadian Rheumatology Association.

To develop and validate the tool, the researchers evaluated 635 patients from the University of Toronto Psoriasis Cohort, which was launched in 2006 as a prospective longitudinal cohort study to examine risk factors for the development of PsA among patients with psoriasis. Patients enrolled in the cohort have a dermatologist-confirmed diagnosis of psoriasis and are assessed by a rheumatologist prior to enrollment to exclude those with inflammatory arthritis in the past or at the time of assessment.

To develop prediction models for PsA, Dr. Eder and colleagues used information from the patient cohort demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms. Next, they used multivariable logistic regression models adjusting for covariates, duration of psoriasis, and the log duration at risk to estimate the probability of developing PsA within 1-year and 5-year time windows from consecutive study visits.

The mean age of the study participants was 47 years, 76% were White, and 57% were male; and they had psoriasis for a mean of 16 years. The researchers found that 51 patients developed PsA during the 1-year follow-up, and 71 developed PsA during the 5-year follow-up. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (area under the curve, 72.3).

In addition, the risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesions, psoriasis severity, fatigue, pain, and use of systemic non-biologic medication or phototherapy (AUC, 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities.

“Interestingly, several previously reported risk factors for PsA, such as HLA-B27, family history of PsA, uveitis, and flexural psoriasis, were not included in the risk prediction model due to their scarcity in our cohort,” the researchers wrote. “This finding may be due to immortal time bias which can complicate the development of risk prediction models for PsA. Genetic factors or their surrogates (e.g., family history of PsA) are associated with the development of PsA concurrently or shortly after the onset of psoriasis.”

They acknowledged certain limitations of the study, including its relatively small sample size and questionable generalizability of the study findings, “as most of the patients were recruited from dermatology clinics leading to overrepresentation of moderate-severe psoriasis. Therefore, PRESTO will require an external validation to assess its performance in other populations of psoriasis patients with different characteristics.”

Saakshi Khattri, MD, a board-certified dermatologist, rheumatologist, and internist at the Icahn School of Medicine at Mount Sinai, New York, who was not involved in the study and was asked to comment on the results, characterized the PRESTO tool as “an interesting step in the right direction, but it’s the first step.”

courtesy Dr. Saakshi Khattri

Since dermatologists are usually the first point of contact for psoriasis patients, she added, “a risk calculator can be helpful, but the question remains: When do we refer them to a rheumatologist? If the risk comes to 5%, is that a low risk that doesn’t need referral to rheumatology? I don’t think those questions have been answered here. From a rheumatology perspective, does the risk calculator help me decide when to intervene? At present, I’m not sure it does. Perhaps a higher score might make us intervene sooner if our clinical exam doesn’t show swollen or tender joints.”

Clinical exam findings and history she considers as a rheumatologist before making treatment recommendations include the following: Are there swollen and tender joints? Does the patient report morning stiffness for upwards of 30 minutes? Do they have enthesitis or dactylitis? Is there axial involvement? “Imaging can help if there isn’t anything on clinical exam and the history is compelling and/or the patient has risk factors for PsA,” she said.

The study’s finding of biologic use being associated with risk of developing PsA at year 1 but not at year 5 is “confusing,” Dr. Khattri added. “My concern is, will that now dissuade our moderate to severe psoriasis patients from using biologics to clear their psoriasis? We know that biologics are indicated for moderate to severe psoriasis. We also know psoriasis is associated with increased cardiovascular risk and there’s data to suggest that treatment with biologics with its resultant decrease in systemic inflammation can decrease cardiovascular risk.”

The study was supported by a New Investigator Grant from the Physician Services Incorporated Foundation. Dr. Eder disclosed that she is supported by the Canada Research Chair in Inflammatory Rheumatic Diseases. Dr. Khattri reported that she is a member of the advisory board for UCB, Janssen, AbbVie, Regeneron, Sanofi, Lilly, Argenx, and Arcutis. She has also received research funds from Incyte, AbbVie, Leo, Galderma, Pfizer, and Acelyrin.

A new predictive tool known as the Psoriatic Arthritis Risk Estimation Tool (PRESTO) is now available to help clinicians estimate the risk of psoriatic arthritis (PsA) in their patients with psoriasis.

Though it requires further validation, researchers led by rheumatologist Lihi Eder, MD, PhD, of the Women’s College Research Institute at Women’s College Hospital, Toronto, characterized the development and validation of PRESTO as “an important first step in the development and testing of interventional strategies that may ultimately halt disease progression,” they wrote in their study of the tool, which published in Arthritis & Rheumatology. Dr. Eder presented a summary of progress on the effort at the 2023 annual meeting of the Canadian Rheumatology Association.

To develop and validate the tool, the researchers evaluated 635 patients from the University of Toronto Psoriasis Cohort, which was launched in 2006 as a prospective longitudinal cohort study to examine risk factors for the development of PsA among patients with psoriasis. Patients enrolled in the cohort have a dermatologist-confirmed diagnosis of psoriasis and are assessed by a rheumatologist prior to enrollment to exclude those with inflammatory arthritis in the past or at the time of assessment.

To develop prediction models for PsA, Dr. Eder and colleagues used information from the patient cohort demographics, psoriasis characteristics, comorbidities, medications, and musculoskeletal symptoms. Next, they used multivariable logistic regression models adjusting for covariates, duration of psoriasis, and the log duration at risk to estimate the probability of developing PsA within 1-year and 5-year time windows from consecutive study visits.

The mean age of the study participants was 47 years, 76% were White, and 57% were male; and they had psoriasis for a mean of 16 years. The researchers found that 51 patients developed PsA during the 1-year follow-up, and 71 developed PsA during the 5-year follow-up. The risk of developing PsA within 1 year was associated with younger age, male sex, family history of psoriasis, back stiffness, nail pitting, joint stiffness, use of biologic medications, patient global health, and pain severity (area under the curve, 72.3).

In addition, the risk of developing PsA within 5 years was associated with morning stiffness, psoriatic nail lesions, psoriasis severity, fatigue, pain, and use of systemic non-biologic medication or phototherapy (AUC, 74.9). Calibration plots showed reasonable agreement between predicted and observed probabilities.

“Interestingly, several previously reported risk factors for PsA, such as HLA-B27, family history of PsA, uveitis, and flexural psoriasis, were not included in the risk prediction model due to their scarcity in our cohort,” the researchers wrote. “This finding may be due to immortal time bias which can complicate the development of risk prediction models for PsA. Genetic factors or their surrogates (e.g., family history of PsA) are associated with the development of PsA concurrently or shortly after the onset of psoriasis.”

They acknowledged certain limitations of the study, including its relatively small sample size and questionable generalizability of the study findings, “as most of the patients were recruited from dermatology clinics leading to overrepresentation of moderate-severe psoriasis. Therefore, PRESTO will require an external validation to assess its performance in other populations of psoriasis patients with different characteristics.”

Saakshi Khattri, MD, a board-certified dermatologist, rheumatologist, and internist at the Icahn School of Medicine at Mount Sinai, New York, who was not involved in the study and was asked to comment on the results, characterized the PRESTO tool as “an interesting step in the right direction, but it’s the first step.”

courtesy Dr. Saakshi Khattri

Since dermatologists are usually the first point of contact for psoriasis patients, she added, “a risk calculator can be helpful, but the question remains: When do we refer them to a rheumatologist? If the risk comes to 5%, is that a low risk that doesn’t need referral to rheumatology? I don’t think those questions have been answered here. From a rheumatology perspective, does the risk calculator help me decide when to intervene? At present, I’m not sure it does. Perhaps a higher score might make us intervene sooner if our clinical exam doesn’t show swollen or tender joints.”

Clinical exam findings and history she considers as a rheumatologist before making treatment recommendations include the following: Are there swollen and tender joints? Does the patient report morning stiffness for upwards of 30 minutes? Do they have enthesitis or dactylitis? Is there axial involvement? “Imaging can help if there isn’t anything on clinical exam and the history is compelling and/or the patient has risk factors for PsA,” she said.

The study’s finding of biologic use being associated with risk of developing PsA at year 1 but not at year 5 is “confusing,” Dr. Khattri added. “My concern is, will that now dissuade our moderate to severe psoriasis patients from using biologics to clear their psoriasis? We know that biologics are indicated for moderate to severe psoriasis. We also know psoriasis is associated with increased cardiovascular risk and there’s data to suggest that treatment with biologics with its resultant decrease in systemic inflammation can decrease cardiovascular risk.”

The study was supported by a New Investigator Grant from the Physician Services Incorporated Foundation. Dr. Eder disclosed that she is supported by the Canada Research Chair in Inflammatory Rheumatic Diseases. Dr. Khattri reported that she is a member of the advisory board for UCB, Janssen, AbbVie, Regeneron, Sanofi, Lilly, Argenx, and Arcutis. She has also received research funds from Incyte, AbbVie, Leo, Galderma, Pfizer, and Acelyrin.

Exocrine pancreatic insufficiency (EPI) may be more common in both type 1 and type 2 diabetes than is currently appreciated, a new literature review suggests.

The condition – in which the pancreas fails to produce sufficient enzymes to fully digest food – can cause gastrointestinal symptoms, including steatorrhea or other stool changes, bloating, and/or abdominal pain. The preferred test for diagnosis is a 72-hour fecal fat quantification test, but fecal elastase-1 is a less invasive and reliable alternative; values of less than 200 mcg/g indicate EPI. Treatment is pancreatic enzyme replacement therapy (PERT), taken with every meal.

EPI occurs in up to 90% of people with cystic fibrosis and chronic pancreatitis and is commonly associated with acute pancreatitis, autoimmune pancreatitis, and pancreatic cancer. However, those conditions are relatively rare compared to diabetes, yet the EPI association with diabetes is less well-studied, Dana M. Lewis, BA, points out in her review article.

While the data vary across studies, owing to differences in inclusion and exclusion criteria, the overall median prevalence of EPI was 33% among patients with type 1 diabetes (range, 14%-77.5%) and 29% among patients with type 2 diabetes (range, 16.8%-49.2%), Ms. Lewis reports in the article, which was published in Diabetes Technology and Therapeutics.

“Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes who present with gastrointestinal symptoms – such as steatorrhea or changes in stool, bloating, and/or abdominal pain – should be screened for EPI. Diabetes specialists, gastroenterologists, and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms,” Ms. Lewis writes.

Since the publication of her article, Ms. Lewis told this news organization, “I’ve gotten feedback from multiple diabetes and general providers that they will be changing their practice as a result of this paper, by screening people with diabetes who have GI symptoms for EPI, which is wonderful to hear.”

In addition, she noted that since she began blogging about EPI and diabetes last year following her own delayed diagnosis, “I have had at least half a dozen people with diabetes tell me that they’ve since sought screening for EPI after years of GI symptoms and ended up being diagnosed with EPI as well.”

Asked to comment, Romesh Khardori, MD, PhD, said in an interview, “it would be prudent to investigate EPI and treat it when confirmed. Consultation with a gastroenterologist colleague may be helpful. Treatment is quite rewarding.”
 

Data limitations; and don’t forget celiac disease and gastroparesis

However, as does Ms. Lewis, Dr. Khardori points to the limitations of the current literature.

“This review suffers from the lack of uniformity amongst the studies in terms of diagnosis and documentation of exocrine pancreatic insufficiency. Many studies lack a control group to draw any meaningful conclusions. Correlations with duration of diabetes, age of onset, symptoms, and glycemic control were mostly lacking,” says Dr. Khardori, now retired but formerly professor of medicine: endocrinology and metabolism at Eastern Virginia Medical School, Norfolk.

In general, the data suggest that PERT is safe and effective for people with diabetes and that it may reduce glycemic variability. However, “there are not many studies looking at glucose outcomes in detail, and only one study that has used CGM [continuous glucose monitoring] data, so this is a big area of need for future study,” Ms. Lewis told this news organization.

Ms. Lewis also reviewed the literature on the prevalence of two other diabetes-related gastrointestinal conditions, celiac disease and gastroparesis, “because anecdotally, it seems as though diabetes care providers and people with diabetes are more aware of those as causes of GI symptoms.”

In type 1 diabetes, the prevalence of both celiac disease and gastroparesis are reported at about 5%, in contrast to the 33% for EPI. Similarly, in type 2 diabetes, the reported prevalence of these two conditions are 1.3% and 1.6%, respectively, vs. 29% for EPI.

“This suggests to me that there is likely disproportionate screening for things like celiac [disease] and gastroparesis in diabetes, and that screening for EPI when people with diabetes present with GI symptoms is warranted,” Ms. Lewis said.

However, Dr. Khardori cautioned that those conditions may also be missed, noting, “Celiac disease often is undiagnosed and gastropathy or gastroparesis may be overlooked in a busy primary care clinic where most patients with diabetes mellitus get their care.”

Ms. Lewis and Dr. Khardori have disclosed no relevant financial relationships.

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

Exocrine pancreatic insufficiency (EPI) may be more common in both type 1 and type 2 diabetes than is currently appreciated, a new literature review suggests.

The condition – in which the pancreas fails to produce sufficient enzymes to fully digest food – can cause gastrointestinal symptoms, including steatorrhea or other stool changes, bloating, and/or abdominal pain. The preferred test for diagnosis is a 72-hour fecal fat quantification test, but fecal elastase-1 is a less invasive and reliable alternative; values of less than 200 mcg/g indicate EPI. Treatment is pancreatic enzyme replacement therapy (PERT), taken with every meal.

EPI occurs in up to 90% of people with cystic fibrosis and chronic pancreatitis and is commonly associated with acute pancreatitis, autoimmune pancreatitis, and pancreatic cancer. However, those conditions are relatively rare compared to diabetes, yet the EPI association with diabetes is less well-studied, Dana M. Lewis, BA, points out in her review article.

While the data vary across studies, owing to differences in inclusion and exclusion criteria, the overall median prevalence of EPI was 33% among patients with type 1 diabetes (range, 14%-77.5%) and 29% among patients with type 2 diabetes (range, 16.8%-49.2%), Ms. Lewis reports in the article, which was published in Diabetes Technology and Therapeutics.

“Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes who present with gastrointestinal symptoms – such as steatorrhea or changes in stool, bloating, and/or abdominal pain – should be screened for EPI. Diabetes specialists, gastroenterologists, and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms,” Ms. Lewis writes.

Since the publication of her article, Ms. Lewis told this news organization, “I’ve gotten feedback from multiple diabetes and general providers that they will be changing their practice as a result of this paper, by screening people with diabetes who have GI symptoms for EPI, which is wonderful to hear.”

In addition, she noted that since she began blogging about EPI and diabetes last year following her own delayed diagnosis, “I have had at least half a dozen people with diabetes tell me that they’ve since sought screening for EPI after years of GI symptoms and ended up being diagnosed with EPI as well.”

Asked to comment, Romesh Khardori, MD, PhD, said in an interview, “it would be prudent to investigate EPI and treat it when confirmed. Consultation with a gastroenterologist colleague may be helpful. Treatment is quite rewarding.”
 

Data limitations; and don’t forget celiac disease and gastroparesis

However, as does Ms. Lewis, Dr. Khardori points to the limitations of the current literature.

“This review suffers from the lack of uniformity amongst the studies in terms of diagnosis and documentation of exocrine pancreatic insufficiency. Many studies lack a control group to draw any meaningful conclusions. Correlations with duration of diabetes, age of onset, symptoms, and glycemic control were mostly lacking,” says Dr. Khardori, now retired but formerly professor of medicine: endocrinology and metabolism at Eastern Virginia Medical School, Norfolk.

In general, the data suggest that PERT is safe and effective for people with diabetes and that it may reduce glycemic variability. However, “there are not many studies looking at glucose outcomes in detail, and only one study that has used CGM [continuous glucose monitoring] data, so this is a big area of need for future study,” Ms. Lewis told this news organization.

Ms. Lewis also reviewed the literature on the prevalence of two other diabetes-related gastrointestinal conditions, celiac disease and gastroparesis, “because anecdotally, it seems as though diabetes care providers and people with diabetes are more aware of those as causes of GI symptoms.”

In type 1 diabetes, the prevalence of both celiac disease and gastroparesis are reported at about 5%, in contrast to the 33% for EPI. Similarly, in type 2 diabetes, the reported prevalence of these two conditions are 1.3% and 1.6%, respectively, vs. 29% for EPI.

“This suggests to me that there is likely disproportionate screening for things like celiac [disease] and gastroparesis in diabetes, and that screening for EPI when people with diabetes present with GI symptoms is warranted,” Ms. Lewis said.

However, Dr. Khardori cautioned that those conditions may also be missed, noting, “Celiac disease often is undiagnosed and gastropathy or gastroparesis may be overlooked in a busy primary care clinic where most patients with diabetes mellitus get their care.”

Ms. Lewis and Dr. Khardori have disclosed no relevant financial relationships.

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

Exocrine pancreatic insufficiency (EPI) may be more common in both type 1 and type 2 diabetes than is currently appreciated, a new literature review suggests.

The condition – in which the pancreas fails to produce sufficient enzymes to fully digest food – can cause gastrointestinal symptoms, including steatorrhea or other stool changes, bloating, and/or abdominal pain. The preferred test for diagnosis is a 72-hour fecal fat quantification test, but fecal elastase-1 is a less invasive and reliable alternative; values of less than 200 mcg/g indicate EPI. Treatment is pancreatic enzyme replacement therapy (PERT), taken with every meal.

EPI occurs in up to 90% of people with cystic fibrosis and chronic pancreatitis and is commonly associated with acute pancreatitis, autoimmune pancreatitis, and pancreatic cancer. However, those conditions are relatively rare compared to diabetes, yet the EPI association with diabetes is less well-studied, Dana M. Lewis, BA, points out in her review article.

While the data vary across studies, owing to differences in inclusion and exclusion criteria, the overall median prevalence of EPI was 33% among patients with type 1 diabetes (range, 14%-77.5%) and 29% among patients with type 2 diabetes (range, 16.8%-49.2%), Ms. Lewis reports in the article, which was published in Diabetes Technology and Therapeutics.

“Cumulatively, this suggests there may be significant numbers of people with diabetes with EPI who are undiagnosed. People with diabetes who present with gastrointestinal symptoms – such as steatorrhea or changes in stool, bloating, and/or abdominal pain – should be screened for EPI. Diabetes specialists, gastroenterologists, and primary care providers should be aware of the high rates of prevalence of diabetes and EPI and recommend fecal elastase-1 screening for people with diabetes and GI symptoms,” Ms. Lewis writes.

Since the publication of her article, Ms. Lewis told this news organization, “I’ve gotten feedback from multiple diabetes and general providers that they will be changing their practice as a result of this paper, by screening people with diabetes who have GI symptoms for EPI, which is wonderful to hear.”

In addition, she noted that since she began blogging about EPI and diabetes last year following her own delayed diagnosis, “I have had at least half a dozen people with diabetes tell me that they’ve since sought screening for EPI after years of GI symptoms and ended up being diagnosed with EPI as well.”

Asked to comment, Romesh Khardori, MD, PhD, said in an interview, “it would be prudent to investigate EPI and treat it when confirmed. Consultation with a gastroenterologist colleague may be helpful. Treatment is quite rewarding.”
 

Data limitations; and don’t forget celiac disease and gastroparesis

However, as does Ms. Lewis, Dr. Khardori points to the limitations of the current literature.

“This review suffers from the lack of uniformity amongst the studies in terms of diagnosis and documentation of exocrine pancreatic insufficiency. Many studies lack a control group to draw any meaningful conclusions. Correlations with duration of diabetes, age of onset, symptoms, and glycemic control were mostly lacking,” says Dr. Khardori, now retired but formerly professor of medicine: endocrinology and metabolism at Eastern Virginia Medical School, Norfolk.

In general, the data suggest that PERT is safe and effective for people with diabetes and that it may reduce glycemic variability. However, “there are not many studies looking at glucose outcomes in detail, and only one study that has used CGM [continuous glucose monitoring] data, so this is a big area of need for future study,” Ms. Lewis told this news organization.

Ms. Lewis also reviewed the literature on the prevalence of two other diabetes-related gastrointestinal conditions, celiac disease and gastroparesis, “because anecdotally, it seems as though diabetes care providers and people with diabetes are more aware of those as causes of GI symptoms.”

In type 1 diabetes, the prevalence of both celiac disease and gastroparesis are reported at about 5%, in contrast to the 33% for EPI. Similarly, in type 2 diabetes, the reported prevalence of these two conditions are 1.3% and 1.6%, respectively, vs. 29% for EPI.

“This suggests to me that there is likely disproportionate screening for things like celiac [disease] and gastroparesis in diabetes, and that screening for EPI when people with diabetes present with GI symptoms is warranted,” Ms. Lewis said.

However, Dr. Khardori cautioned that those conditions may also be missed, noting, “Celiac disease often is undiagnosed and gastropathy or gastroparesis may be overlooked in a busy primary care clinic where most patients with diabetes mellitus get their care.”

Ms. Lewis and Dr. Khardori have disclosed no relevant financial relationships.

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

Presenting obesity as a chronic medical condition, rather than as a failure to eat less and move more, may improve self-esteem among patients with obesity and enhance their relationships with their doctors, a new study suggests.

In an online study, patients with obesity reported significantly less internalized weight bias and significantly enhanced perceptions of positive communication with their medical providers after watching a video of a doctor who framed obesity as a treatable medical condition, compared with a video of a doctor who emphasized willpower.

“Recent research has identified the dominant role that biology (both genetics as well as homeostatic, hedonic, and executive brain systems) and environment, rather than willpower, play in the development of obesity and the resistance to weight loss,” wrote study authors Sara English, a medical student, and Michael Vallis, MD, associate professor of family medicine, both at Dalhousie University, Halifax, N.S. “Yet the false narrative that ideal or goal weight can be achieved by eating less and moving more using willpower continues to dominate the public narrative.”

The findings were published in Clinical Obesity.
 

Medical complexity

The public discussion generally places all responsibility for the health outcomes of obesity on the patient. As a result, patients with obesity face bias and stigma from the public and the health care system, wrote the authors.

This stigmatization contributes to increased mortality and morbidity by promoting maladaptive eating behaviors and stress. It also causes mistrust of health care professionals, which, in turn, leads to worse health outcomes and increased health care costs.

The 2020 Canadian clinical practice guidelines for obesity management in adults emphasize that obesity is complex and that nonbehavioral factors strongly influence it. They recommend that treatment focus on improving patient-centered health outcomes and address the root causes of obesity, instead of focusing on weight loss alone.

In the present study, Ms. English and Dr. Vallis evaluated how presenting obesity as a treatable medical condition affected participants’ internalized weight bias and their perceived relationship with their health care provider. They asked 61 patients with obesity (average age, 49 years; average body mass index, 41 kg/m²) to watch two videos, the first showing a doctor endorsing the traditional “eat less, move more approach,” and the second showing a doctor describing obesity as a chronic, treatable medical condition.

Nearly half (49.5%) of participants reported that their health care provider rarely or never discusses weight loss, and almost two-thirds of participants (64%) reported feeling stigmatized by their health care provider because of their weight at least some of the time.

After having watched each video, participants were asked to imagine that they were being treated by the corresponding doctor and to complete two measures: the Weight Bias Internalization Scale (WBIS), which measures the degree to which a respondent believes the negative stereotypes about obese people, and the Patient-Health Care Provider Communication Scale (PHCPCS), which assesses the quality of patient–health care provider communication.

Virtually all participants preferred the care provider in the video with the revised presentation of obesity. Only one preferred the traditional video. The video with the revised presentation was associated with significant reductions in internalized weight bias. Participants’ WBIS total score decreased from 4.49 to 3.36 (P < .001). The revised narrative video also had a positive effect on patients’ perception of their health care providers. The PHCPCS total score increased from 2.65 to 4.20 (P < .001).
 

A chronic disease

In a comment, Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, said: “If you’re asking me if it is a good idea to treat obesity like a chronic disease, the answer would be yes, we absolutely should. It is a chronic disease, and it shouldn’t have a treatment paradigm different from the other chronic diseases.” Dr. Freedhoff did not participate in the study.

“We certainly don’t blame patients for having other chronic conditions,” Dr. Freedhoff added. “We don’t have a narrative that, in order for them to qualify for medication or other treatment options, they have to audition for them by failing lifestyle approaches first. And yet, I’d say at least 85% of chronic noncommunicable diseases have lifestyle factors, but obesity is the only one where we consider that there is a necessity for these lifestyle changes, as if there have been studies demonstrating durable and reproducible outcomes for lifestyle in obesity. There have not.” 

Telling patients and doctors that obesity is a chronic disease driven by biology, not a failure of willpower, is going to reduce stigma, “which is what this study was able to demonstrate to some degree,” Dr. Freedhoff said.

“What is more stigmatizing? Being told that if you just try hard enough, you’ll succeed, and if you don’t succeed, the corollary, of course, is that you did not try hard enough? Versus, you’ve got a medical condition where you’ve got biological drivers beyond your locus of control, affecting behaviors that, in turn, contribute to your adiposity? I’m pretty sure the second statement will have far less impact on a person’s internalized weight bias than what we’ve unfortunately been doing up until now with the focus on willpower,” Dr. Freedhoff said.

No funding for the study was reported. Ms. English and Dr. Vallis reported no relevant financial relationships. Dr. Freedhoff reported receiving clinical grants from Novo Nordisk.

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

Presenting obesity as a chronic medical condition, rather than as a failure to eat less and move more, may improve self-esteem among patients with obesity and enhance their relationships with their doctors, a new study suggests.

In an online study, patients with obesity reported significantly less internalized weight bias and significantly enhanced perceptions of positive communication with their medical providers after watching a video of a doctor who framed obesity as a treatable medical condition, compared with a video of a doctor who emphasized willpower.

“Recent research has identified the dominant role that biology (both genetics as well as homeostatic, hedonic, and executive brain systems) and environment, rather than willpower, play in the development of obesity and the resistance to weight loss,” wrote study authors Sara English, a medical student, and Michael Vallis, MD, associate professor of family medicine, both at Dalhousie University, Halifax, N.S. “Yet the false narrative that ideal or goal weight can be achieved by eating less and moving more using willpower continues to dominate the public narrative.”

The findings were published in Clinical Obesity.
 

Medical complexity

The public discussion generally places all responsibility for the health outcomes of obesity on the patient. As a result, patients with obesity face bias and stigma from the public and the health care system, wrote the authors.

This stigmatization contributes to increased mortality and morbidity by promoting maladaptive eating behaviors and stress. It also causes mistrust of health care professionals, which, in turn, leads to worse health outcomes and increased health care costs.

The 2020 Canadian clinical practice guidelines for obesity management in adults emphasize that obesity is complex and that nonbehavioral factors strongly influence it. They recommend that treatment focus on improving patient-centered health outcomes and address the root causes of obesity, instead of focusing on weight loss alone.

In the present study, Ms. English and Dr. Vallis evaluated how presenting obesity as a treatable medical condition affected participants’ internalized weight bias and their perceived relationship with their health care provider. They asked 61 patients with obesity (average age, 49 years; average body mass index, 41 kg/m²) to watch two videos, the first showing a doctor endorsing the traditional “eat less, move more approach,” and the second showing a doctor describing obesity as a chronic, treatable medical condition.

Nearly half (49.5%) of participants reported that their health care provider rarely or never discusses weight loss, and almost two-thirds of participants (64%) reported feeling stigmatized by their health care provider because of their weight at least some of the time.

After having watched each video, participants were asked to imagine that they were being treated by the corresponding doctor and to complete two measures: the Weight Bias Internalization Scale (WBIS), which measures the degree to which a respondent believes the negative stereotypes about obese people, and the Patient-Health Care Provider Communication Scale (PHCPCS), which assesses the quality of patient–health care provider communication.

Virtually all participants preferred the care provider in the video with the revised presentation of obesity. Only one preferred the traditional video. The video with the revised presentation was associated with significant reductions in internalized weight bias. Participants’ WBIS total score decreased from 4.49 to 3.36 (P < .001). The revised narrative video also had a positive effect on patients’ perception of their health care providers. The PHCPCS total score increased from 2.65 to 4.20 (P < .001).
 

A chronic disease

In a comment, Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, said: “If you’re asking me if it is a good idea to treat obesity like a chronic disease, the answer would be yes, we absolutely should. It is a chronic disease, and it shouldn’t have a treatment paradigm different from the other chronic diseases.” Dr. Freedhoff did not participate in the study.

“We certainly don’t blame patients for having other chronic conditions,” Dr. Freedhoff added. “We don’t have a narrative that, in order for them to qualify for medication or other treatment options, they have to audition for them by failing lifestyle approaches first. And yet, I’d say at least 85% of chronic noncommunicable diseases have lifestyle factors, but obesity is the only one where we consider that there is a necessity for these lifestyle changes, as if there have been studies demonstrating durable and reproducible outcomes for lifestyle in obesity. There have not.” 

Telling patients and doctors that obesity is a chronic disease driven by biology, not a failure of willpower, is going to reduce stigma, “which is what this study was able to demonstrate to some degree,” Dr. Freedhoff said.

“What is more stigmatizing? Being told that if you just try hard enough, you’ll succeed, and if you don’t succeed, the corollary, of course, is that you did not try hard enough? Versus, you’ve got a medical condition where you’ve got biological drivers beyond your locus of control, affecting behaviors that, in turn, contribute to your adiposity? I’m pretty sure the second statement will have far less impact on a person’s internalized weight bias than what we’ve unfortunately been doing up until now with the focus on willpower,” Dr. Freedhoff said.

No funding for the study was reported. Ms. English and Dr. Vallis reported no relevant financial relationships. Dr. Freedhoff reported receiving clinical grants from Novo Nordisk.

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

Presenting obesity as a chronic medical condition, rather than as a failure to eat less and move more, may improve self-esteem among patients with obesity and enhance their relationships with their doctors, a new study suggests.

In an online study, patients with obesity reported significantly less internalized weight bias and significantly enhanced perceptions of positive communication with their medical providers after watching a video of a doctor who framed obesity as a treatable medical condition, compared with a video of a doctor who emphasized willpower.

“Recent research has identified the dominant role that biology (both genetics as well as homeostatic, hedonic, and executive brain systems) and environment, rather than willpower, play in the development of obesity and the resistance to weight loss,” wrote study authors Sara English, a medical student, and Michael Vallis, MD, associate professor of family medicine, both at Dalhousie University, Halifax, N.S. “Yet the false narrative that ideal or goal weight can be achieved by eating less and moving more using willpower continues to dominate the public narrative.”

The findings were published in Clinical Obesity.
 

Medical complexity

The public discussion generally places all responsibility for the health outcomes of obesity on the patient. As a result, patients with obesity face bias and stigma from the public and the health care system, wrote the authors.

This stigmatization contributes to increased mortality and morbidity by promoting maladaptive eating behaviors and stress. It also causes mistrust of health care professionals, which, in turn, leads to worse health outcomes and increased health care costs.

The 2020 Canadian clinical practice guidelines for obesity management in adults emphasize that obesity is complex and that nonbehavioral factors strongly influence it. They recommend that treatment focus on improving patient-centered health outcomes and address the root causes of obesity, instead of focusing on weight loss alone.

In the present study, Ms. English and Dr. Vallis evaluated how presenting obesity as a treatable medical condition affected participants’ internalized weight bias and their perceived relationship with their health care provider. They asked 61 patients with obesity (average age, 49 years; average body mass index, 41 kg/m²) to watch two videos, the first showing a doctor endorsing the traditional “eat less, move more approach,” and the second showing a doctor describing obesity as a chronic, treatable medical condition.

Nearly half (49.5%) of participants reported that their health care provider rarely or never discusses weight loss, and almost two-thirds of participants (64%) reported feeling stigmatized by their health care provider because of their weight at least some of the time.

After having watched each video, participants were asked to imagine that they were being treated by the corresponding doctor and to complete two measures: the Weight Bias Internalization Scale (WBIS), which measures the degree to which a respondent believes the negative stereotypes about obese people, and the Patient-Health Care Provider Communication Scale (PHCPCS), which assesses the quality of patient–health care provider communication.

Virtually all participants preferred the care provider in the video with the revised presentation of obesity. Only one preferred the traditional video. The video with the revised presentation was associated with significant reductions in internalized weight bias. Participants’ WBIS total score decreased from 4.49 to 3.36 (P < .001). The revised narrative video also had a positive effect on patients’ perception of their health care providers. The PHCPCS total score increased from 2.65 to 4.20 (P < .001).
 

A chronic disease

In a comment, Yoni Freedhoff, MD, associate professor of family medicine at the University of Ottawa, said: “If you’re asking me if it is a good idea to treat obesity like a chronic disease, the answer would be yes, we absolutely should. It is a chronic disease, and it shouldn’t have a treatment paradigm different from the other chronic diseases.” Dr. Freedhoff did not participate in the study.

“We certainly don’t blame patients for having other chronic conditions,” Dr. Freedhoff added. “We don’t have a narrative that, in order for them to qualify for medication or other treatment options, they have to audition for them by failing lifestyle approaches first. And yet, I’d say at least 85% of chronic noncommunicable diseases have lifestyle factors, but obesity is the only one where we consider that there is a necessity for these lifestyle changes, as if there have been studies demonstrating durable and reproducible outcomes for lifestyle in obesity. There have not.” 

Telling patients and doctors that obesity is a chronic disease driven by biology, not a failure of willpower, is going to reduce stigma, “which is what this study was able to demonstrate to some degree,” Dr. Freedhoff said.

“What is more stigmatizing? Being told that if you just try hard enough, you’ll succeed, and if you don’t succeed, the corollary, of course, is that you did not try hard enough? Versus, you’ve got a medical condition where you’ve got biological drivers beyond your locus of control, affecting behaviors that, in turn, contribute to your adiposity? I’m pretty sure the second statement will have far less impact on a person’s internalized weight bias than what we’ve unfortunately been doing up until now with the focus on willpower,” Dr. Freedhoff said.

No funding for the study was reported. Ms. English and Dr. Vallis reported no relevant financial relationships. Dr. Freedhoff reported receiving clinical grants from Novo Nordisk.

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

Higher daily step counts were associated with reduced risk of all-cause mortality and cardiovascular (CV) mortality, with benefit beginning with any amount over about 4,000 and 2,300 steps, respectively, in a new meta-analysis.
 

More steps were better – additional benefit was seen with increasing increments of 500 or 1,000 steps.

Leonardo Patrizi/E+/Getty Images

“One of our main aims was to overcome all the inconsistencies in previous studies, where the optimal number of daily steps for health benefits was usually between 6,000 and 10,000,” Maciej Banach, MD, PhD, of the Medical University of Lodz (Poland), said in an interview.

“As a preventive cardiologist, I saw that many of my patients were discouraged and said it’s impossible when I told them that making lifestyle changes included taking at least 7,000 daily steps,” he said.

“But our study in relatively healthy individuals, not patients, showed even a lower number – for example, around 4,000 – may be associated with a significant reduction of mortality.

“I tell people to start early, be regular, and don’t worry about the initial baseline number, because it’s important to start and it’s important to improve,” he said. “Our study showed that if we increase the number of steps per day, every 500- to 1,000-step increase might still be associated with an additional mortality reduction of 7%-15%.”

The study was published online in the European Journal of Preventive Cardiology.
 

Every move counts

The investigators searched the literature through June 2022 and selected 17 cohort studies with 226,889 participants and a median follow-up of 7.1 years for inclusion in the analysis: 10 studies reported all-cause mortality, 4 reported CV mortality, and 3 reported both outcomes.

The mean age of the participants was 64.4 years, and half were women. Daily step counts in the included studies were objectively measured for at least 7 consecutive days.

As noted, a 1,000-step increment was associated with a 15% decrease in risk of all-cause mortality (hazard ratio, 0.85); a 500-step increment was associated with a 7% decrease in CV mortality (HR, 0.93).

Compared with the reference quartile (median steps/day, 3,967), quartile 1 (median steps, 5,537) was associated with a 48% lower risk of all-cause mortality; quartile 2 (median steps, 7,370), with a 55% lower risk; and quartile 3 (median steps, 11,529), with a 67% risk reduction.

Similarly, compared with the lowest quartile of steps per day used as reference (median steps, 2,337), higher quartiles of steps per day (Q1, 3,982; Q2, 6,661; and Q3, 10,413) were linearly associated with a reduced risk of CV mortality (16%, 49%, and 77%, respectively).

In a restricted cubic splines model, a nonlinear dose-response association was observed between step count and all-cause and CV mortality, with a progressively lower risk of mortality with an increase in step count.

Dose-response curves were similar for men and women. However, there was a difference by age: Among people aged 60 years or older, the size of the risk reduction was smaller. Among the older adults, there was a 42% risk reduction for those who walked between 6000 and 10,000 steps daily, compared with a 49% reduction in risk among younger adults who walked between 7,000 and 13,000 steps a day.

For both groups, daily step counts higher than 5,000 resulted in a “dramatically” lower risk of all-cause mortality.

An analysis that compared the impact of climate regions on the associations showed no significant effect on all-cause mortality. People in all climate zones benefited when the daily step count exceeded approximately 5,500.

Even given the encouraging study results, “we know very well that every kind of exercise is critically important,” Dr. Banach said. It is easier to focus on step counts because the counts can be monitored and calculated with smartwatches, pedometers, and other tools. That also makes it easier to check associations and outcomes for large groups of patients.

“But in fact, we should not be focusing on one type of exercise, such as walking or running,” he said. “We can dance, ride bicycles, and do many other different exercises that mobilize our hearts.

“We also know that in all these activities, including steps, people have different capabilities – for example, some can walk more slowly, others faster and with more intensity.”

Dr. Banach recommended following the European and U.S. physical activity guidelines that advise, in addition to muscle-strengthening activities, 150 minutes of moderate-intensity aerobic training weekly, or 75 minutes of vigorous-intensity aerobic activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity.

From the results he sees in patients, he believes the combination approach is probably best for the heart.

Furthermore, it’s important to exercise regularly, something that’s easier if individuals enjoy what they’re doing. “The type of training or whether you are completely inactive or very active at the start doesn’t matter, because any improvement, any addition to the to the baseline values will have health benefits,” he concluded.
 

Higher goals helpful

Three experts commented on the study; all noted that the results are in line with previous studies, that the observational nature of the study is a limitation, and that additional randomized, controlled trials are needed to confirm the findings.

Evan Brittain, MD, an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., expressed some additional concerns.

Dr. Brittain was principal investigator of a recent study that found that the relationship between steps per day and incident disease was inverse and linear for obesity, sleep apnea, gastroesophageal reflux disease, and major depressive disorder. Daily step counts above 8,200 were associated with protection from incident disease.

He noted that, in the current study, “the authors chose to make the least active quartile (25%) the reference group (only 3,967 steps/day for all-cause mortality and only 2,337 steps/day for CV mortality analysis), which somewhat lowers the bar for finding a significant benefit at higher step counts.

“Moreover, in the spline analyses, zero steps per day is used as the comparison, which is not a practical, real-world comparison,” he said. “As a result, those data are very hard to interpret, and I think are overstated.”

Like Dr. Banach, Dr. Brittain said he would continue to advise following guideline recommendations to get 150 minutes per week of moderate-intensity activity. However, he added that although it is reasonable to advise patients that benefits do accrue with daily step counts of less than 10,000, “I would not want patients to misconstrue from this study that getting more than only 2,330 steps per day is a beneficial goal.”

Martin Halle, MD, a professor in the department of prevention and sports medicine at the Technical University of Munich (Germany), said: “From a clinical, medical, and health perspective, the general population should aim for 5,000 steps, which is about 3-4 kilometers [about 2 miles] of walking, and intensity counts – the faster you walk, the better.

“I recommend doing 100 steps fast and 100 steps slow and then 100 steps fast and 100 steps slow,” said Dr. Halle, who is past president of the European Association of Preventive Cardiology. This approach not only motivates people, “but they improve their exercise capacity substantially and very quickly, just within weeks.”

European Society of Cardiology vice president and European Journal of Preventive Cardiology editor-in-chief Massimo Piepoli, MD, PhD, agreed that “little is better than nothing and more is even better. This applies to healthy subjects, as well as patients with chronic diseases.

“Five hundred steps is a very short distance (such as walking two blocks or walking the dog for about 10-15 minutes every day),” he said. Yet, increasing step counts in increments of 500 “is associated with a significant reduction in cardiovascular mortality both in men and women, particularly in older individuals.

“We do not need to depend on expensive gym facilities,” he added. “But at the same time, we need to live in and to promote the building of neighborhoods where it is possible to walk in a safe and healthy environment.”

The research received no external funding. Dr. Banach has reported financial relationships with Amgen, Daiichi Sankyo, Esperion, Freia Pharmaceuticals, Kogen, KRKA, Polpharma, NewAmsterdam, Novartis, Novo Nordisk, Polfarmex, Sanofi Aventis, Teva, Valeant, Viatris, and Zentiva, and is chief marketing and development officer at Longevity Group and chief marketing officer at Nomi Biotech.

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

Higher daily step counts were associated with reduced risk of all-cause mortality and cardiovascular (CV) mortality, with benefit beginning with any amount over about 4,000 and 2,300 steps, respectively, in a new meta-analysis.
 

More steps were better – additional benefit was seen with increasing increments of 500 or 1,000 steps.

Leonardo Patrizi/E+/Getty Images

“One of our main aims was to overcome all the inconsistencies in previous studies, where the optimal number of daily steps for health benefits was usually between 6,000 and 10,000,” Maciej Banach, MD, PhD, of the Medical University of Lodz (Poland), said in an interview.

“As a preventive cardiologist, I saw that many of my patients were discouraged and said it’s impossible when I told them that making lifestyle changes included taking at least 7,000 daily steps,” he said.

“But our study in relatively healthy individuals, not patients, showed even a lower number – for example, around 4,000 – may be associated with a significant reduction of mortality.

“I tell people to start early, be regular, and don’t worry about the initial baseline number, because it’s important to start and it’s important to improve,” he said. “Our study showed that if we increase the number of steps per day, every 500- to 1,000-step increase might still be associated with an additional mortality reduction of 7%-15%.”

The study was published online in the European Journal of Preventive Cardiology.
 

Every move counts

The investigators searched the literature through June 2022 and selected 17 cohort studies with 226,889 participants and a median follow-up of 7.1 years for inclusion in the analysis: 10 studies reported all-cause mortality, 4 reported CV mortality, and 3 reported both outcomes.

The mean age of the participants was 64.4 years, and half were women. Daily step counts in the included studies were objectively measured for at least 7 consecutive days.

As noted, a 1,000-step increment was associated with a 15% decrease in risk of all-cause mortality (hazard ratio, 0.85); a 500-step increment was associated with a 7% decrease in CV mortality (HR, 0.93).

Compared with the reference quartile (median steps/day, 3,967), quartile 1 (median steps, 5,537) was associated with a 48% lower risk of all-cause mortality; quartile 2 (median steps, 7,370), with a 55% lower risk; and quartile 3 (median steps, 11,529), with a 67% risk reduction.

Similarly, compared with the lowest quartile of steps per day used as reference (median steps, 2,337), higher quartiles of steps per day (Q1, 3,982; Q2, 6,661; and Q3, 10,413) were linearly associated with a reduced risk of CV mortality (16%, 49%, and 77%, respectively).

In a restricted cubic splines model, a nonlinear dose-response association was observed between step count and all-cause and CV mortality, with a progressively lower risk of mortality with an increase in step count.

Dose-response curves were similar for men and women. However, there was a difference by age: Among people aged 60 years or older, the size of the risk reduction was smaller. Among the older adults, there was a 42% risk reduction for those who walked between 6000 and 10,000 steps daily, compared with a 49% reduction in risk among younger adults who walked between 7,000 and 13,000 steps a day.

For both groups, daily step counts higher than 5,000 resulted in a “dramatically” lower risk of all-cause mortality.

An analysis that compared the impact of climate regions on the associations showed no significant effect on all-cause mortality. People in all climate zones benefited when the daily step count exceeded approximately 5,500.

Even given the encouraging study results, “we know very well that every kind of exercise is critically important,” Dr. Banach said. It is easier to focus on step counts because the counts can be monitored and calculated with smartwatches, pedometers, and other tools. That also makes it easier to check associations and outcomes for large groups of patients.

“But in fact, we should not be focusing on one type of exercise, such as walking or running,” he said. “We can dance, ride bicycles, and do many other different exercises that mobilize our hearts.

“We also know that in all these activities, including steps, people have different capabilities – for example, some can walk more slowly, others faster and with more intensity.”

Dr. Banach recommended following the European and U.S. physical activity guidelines that advise, in addition to muscle-strengthening activities, 150 minutes of moderate-intensity aerobic training weekly, or 75 minutes of vigorous-intensity aerobic activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity.

From the results he sees in patients, he believes the combination approach is probably best for the heart.

Furthermore, it’s important to exercise regularly, something that’s easier if individuals enjoy what they’re doing. “The type of training or whether you are completely inactive or very active at the start doesn’t matter, because any improvement, any addition to the to the baseline values will have health benefits,” he concluded.
 

Higher goals helpful

Three experts commented on the study; all noted that the results are in line with previous studies, that the observational nature of the study is a limitation, and that additional randomized, controlled trials are needed to confirm the findings.

Evan Brittain, MD, an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., expressed some additional concerns.

Dr. Brittain was principal investigator of a recent study that found that the relationship between steps per day and incident disease was inverse and linear for obesity, sleep apnea, gastroesophageal reflux disease, and major depressive disorder. Daily step counts above 8,200 were associated with protection from incident disease.

He noted that, in the current study, “the authors chose to make the least active quartile (25%) the reference group (only 3,967 steps/day for all-cause mortality and only 2,337 steps/day for CV mortality analysis), which somewhat lowers the bar for finding a significant benefit at higher step counts.

“Moreover, in the spline analyses, zero steps per day is used as the comparison, which is not a practical, real-world comparison,” he said. “As a result, those data are very hard to interpret, and I think are overstated.”

Like Dr. Banach, Dr. Brittain said he would continue to advise following guideline recommendations to get 150 minutes per week of moderate-intensity activity. However, he added that although it is reasonable to advise patients that benefits do accrue with daily step counts of less than 10,000, “I would not want patients to misconstrue from this study that getting more than only 2,330 steps per day is a beneficial goal.”

Martin Halle, MD, a professor in the department of prevention and sports medicine at the Technical University of Munich (Germany), said: “From a clinical, medical, and health perspective, the general population should aim for 5,000 steps, which is about 3-4 kilometers [about 2 miles] of walking, and intensity counts – the faster you walk, the better.

“I recommend doing 100 steps fast and 100 steps slow and then 100 steps fast and 100 steps slow,” said Dr. Halle, who is past president of the European Association of Preventive Cardiology. This approach not only motivates people, “but they improve their exercise capacity substantially and very quickly, just within weeks.”

European Society of Cardiology vice president and European Journal of Preventive Cardiology editor-in-chief Massimo Piepoli, MD, PhD, agreed that “little is better than nothing and more is even better. This applies to healthy subjects, as well as patients with chronic diseases.

“Five hundred steps is a very short distance (such as walking two blocks or walking the dog for about 10-15 minutes every day),” he said. Yet, increasing step counts in increments of 500 “is associated with a significant reduction in cardiovascular mortality both in men and women, particularly in older individuals.

“We do not need to depend on expensive gym facilities,” he added. “But at the same time, we need to live in and to promote the building of neighborhoods where it is possible to walk in a safe and healthy environment.”

The research received no external funding. Dr. Banach has reported financial relationships with Amgen, Daiichi Sankyo, Esperion, Freia Pharmaceuticals, Kogen, KRKA, Polpharma, NewAmsterdam, Novartis, Novo Nordisk, Polfarmex, Sanofi Aventis, Teva, Valeant, Viatris, and Zentiva, and is chief marketing and development officer at Longevity Group and chief marketing officer at Nomi Biotech.

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

Higher daily step counts were associated with reduced risk of all-cause mortality and cardiovascular (CV) mortality, with benefit beginning with any amount over about 4,000 and 2,300 steps, respectively, in a new meta-analysis.
 

More steps were better – additional benefit was seen with increasing increments of 500 or 1,000 steps.

Leonardo Patrizi/E+/Getty Images

“One of our main aims was to overcome all the inconsistencies in previous studies, where the optimal number of daily steps for health benefits was usually between 6,000 and 10,000,” Maciej Banach, MD, PhD, of the Medical University of Lodz (Poland), said in an interview.

“As a preventive cardiologist, I saw that many of my patients were discouraged and said it’s impossible when I told them that making lifestyle changes included taking at least 7,000 daily steps,” he said.

“But our study in relatively healthy individuals, not patients, showed even a lower number – for example, around 4,000 – may be associated with a significant reduction of mortality.

“I tell people to start early, be regular, and don’t worry about the initial baseline number, because it’s important to start and it’s important to improve,” he said. “Our study showed that if we increase the number of steps per day, every 500- to 1,000-step increase might still be associated with an additional mortality reduction of 7%-15%.”

The study was published online in the European Journal of Preventive Cardiology.
 

Every move counts

The investigators searched the literature through June 2022 and selected 17 cohort studies with 226,889 participants and a median follow-up of 7.1 years for inclusion in the analysis: 10 studies reported all-cause mortality, 4 reported CV mortality, and 3 reported both outcomes.

The mean age of the participants was 64.4 years, and half were women. Daily step counts in the included studies were objectively measured for at least 7 consecutive days.

As noted, a 1,000-step increment was associated with a 15% decrease in risk of all-cause mortality (hazard ratio, 0.85); a 500-step increment was associated with a 7% decrease in CV mortality (HR, 0.93).

Compared with the reference quartile (median steps/day, 3,967), quartile 1 (median steps, 5,537) was associated with a 48% lower risk of all-cause mortality; quartile 2 (median steps, 7,370), with a 55% lower risk; and quartile 3 (median steps, 11,529), with a 67% risk reduction.

Similarly, compared with the lowest quartile of steps per day used as reference (median steps, 2,337), higher quartiles of steps per day (Q1, 3,982; Q2, 6,661; and Q3, 10,413) were linearly associated with a reduced risk of CV mortality (16%, 49%, and 77%, respectively).

In a restricted cubic splines model, a nonlinear dose-response association was observed between step count and all-cause and CV mortality, with a progressively lower risk of mortality with an increase in step count.

Dose-response curves were similar for men and women. However, there was a difference by age: Among people aged 60 years or older, the size of the risk reduction was smaller. Among the older adults, there was a 42% risk reduction for those who walked between 6000 and 10,000 steps daily, compared with a 49% reduction in risk among younger adults who walked between 7,000 and 13,000 steps a day.

For both groups, daily step counts higher than 5,000 resulted in a “dramatically” lower risk of all-cause mortality.

An analysis that compared the impact of climate regions on the associations showed no significant effect on all-cause mortality. People in all climate zones benefited when the daily step count exceeded approximately 5,500.

Even given the encouraging study results, “we know very well that every kind of exercise is critically important,” Dr. Banach said. It is easier to focus on step counts because the counts can be monitored and calculated with smartwatches, pedometers, and other tools. That also makes it easier to check associations and outcomes for large groups of patients.

“But in fact, we should not be focusing on one type of exercise, such as walking or running,” he said. “We can dance, ride bicycles, and do many other different exercises that mobilize our hearts.

“We also know that in all these activities, including steps, people have different capabilities – for example, some can walk more slowly, others faster and with more intensity.”

Dr. Banach recommended following the European and U.S. physical activity guidelines that advise, in addition to muscle-strengthening activities, 150 minutes of moderate-intensity aerobic training weekly, or 75 minutes of vigorous-intensity aerobic activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity.

From the results he sees in patients, he believes the combination approach is probably best for the heart.

Furthermore, it’s important to exercise regularly, something that’s easier if individuals enjoy what they’re doing. “The type of training or whether you are completely inactive or very active at the start doesn’t matter, because any improvement, any addition to the to the baseline values will have health benefits,” he concluded.
 

Higher goals helpful

Three experts commented on the study; all noted that the results are in line with previous studies, that the observational nature of the study is a limitation, and that additional randomized, controlled trials are needed to confirm the findings.

Evan Brittain, MD, an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., expressed some additional concerns.

Dr. Brittain was principal investigator of a recent study that found that the relationship between steps per day and incident disease was inverse and linear for obesity, sleep apnea, gastroesophageal reflux disease, and major depressive disorder. Daily step counts above 8,200 were associated with protection from incident disease.

He noted that, in the current study, “the authors chose to make the least active quartile (25%) the reference group (only 3,967 steps/day for all-cause mortality and only 2,337 steps/day for CV mortality analysis), which somewhat lowers the bar for finding a significant benefit at higher step counts.

“Moreover, in the spline analyses, zero steps per day is used as the comparison, which is not a practical, real-world comparison,” he said. “As a result, those data are very hard to interpret, and I think are overstated.”

Like Dr. Banach, Dr. Brittain said he would continue to advise following guideline recommendations to get 150 minutes per week of moderate-intensity activity. However, he added that although it is reasonable to advise patients that benefits do accrue with daily step counts of less than 10,000, “I would not want patients to misconstrue from this study that getting more than only 2,330 steps per day is a beneficial goal.”

Martin Halle, MD, a professor in the department of prevention and sports medicine at the Technical University of Munich (Germany), said: “From a clinical, medical, and health perspective, the general population should aim for 5,000 steps, which is about 3-4 kilometers [about 2 miles] of walking, and intensity counts – the faster you walk, the better.

“I recommend doing 100 steps fast and 100 steps slow and then 100 steps fast and 100 steps slow,” said Dr. Halle, who is past president of the European Association of Preventive Cardiology. This approach not only motivates people, “but they improve their exercise capacity substantially and very quickly, just within weeks.”

European Society of Cardiology vice president and European Journal of Preventive Cardiology editor-in-chief Massimo Piepoli, MD, PhD, agreed that “little is better than nothing and more is even better. This applies to healthy subjects, as well as patients with chronic diseases.

“Five hundred steps is a very short distance (such as walking two blocks or walking the dog for about 10-15 minutes every day),” he said. Yet, increasing step counts in increments of 500 “is associated with a significant reduction in cardiovascular mortality both in men and women, particularly in older individuals.

“We do not need to depend on expensive gym facilities,” he added. “But at the same time, we need to live in and to promote the building of neighborhoods where it is possible to walk in a safe and healthy environment.”

The research received no external funding. Dr. Banach has reported financial relationships with Amgen, Daiichi Sankyo, Esperion, Freia Pharmaceuticals, Kogen, KRKA, Polpharma, NewAmsterdam, Novartis, Novo Nordisk, Polfarmex, Sanofi Aventis, Teva, Valeant, Viatris, and Zentiva, and is chief marketing and development officer at Longevity Group and chief marketing officer at Nomi Biotech.

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

The latest clinical practice guideline for managing patients with chronic coronary disease (CCD) takes an evidence-based and patient-centered approach to care and includes key updates on revascularization, beta-blocker use, and routine functional and anatomic testing.

Developed by the American Heart Association, the American College of Cardiology, and other specialty societies, the 2023 guideline both updates and consolidates ACC/AHA guidelines previously published in 2012 and 2014 for the management of patients with stable ischemic heart disease.

It was published online in Circulation and the Journal of the American College of Cardiology .

Among the key recommendations were the following.

• Long-term beta-blocker therapy is no longer recommended for improving outcomes for patients with CCD in the absence of myocardial infarction within the past year, left ventricular ejection fraction (LVEF) less than or equal to 50%, or another primary indication for beta-blocker therapy. Either a calcium channel blocker or a beta-blocker is recommended as first-line antianginal therapy.
• Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are recommended for select groups of patients with CCD, including individuals without diabetes, to improve outcomes.
• Statins remain first-line therapy for lipid lowering for patients with CCD. Several adjunctive therapies, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, or bempedoic acid, may be used in select populations, although clinical outcomes data are not yet available for novel agents such as inclisiran and bempedoic acid.
• Shorter durations of dual antiplatelet therapy are safe and effective in many circumstances, particularly when the risk of bleeding is high and the ischemic risk is not high.
• The use of nonprescription or dietary supplements, including fish oil and omega-3 fatty acids or vitamins, is not recommended for patients with CCD, given the lack of benefit in reducing cardiovascular events.
• Revascularization is recommended in two scenarios: (1) for patients with lifestyle-limiting angina despite guideline-directed medical therapy and with coronary stenoses amenable to revascularization, with the goal of improving symptoms; and (2) for patients with significant left main disease or multivessel disease with severe LV dysfunction (LVEF ≤ 35%), for whom coronary artery bypass grafting plus medical therapy is recommended over medical therapy alone, with the goal of improving survival.
• Routine periodic anatomic or ischemic testing in the absence of a change in clinical or functional status is not recommended for risk stratification or to guide therapeutic decision-making for patients with CCD.
• Nondrug therapies, including healthy dietary habits and exercise, are recommended for all patients with CCD. When possible, patients should participate in regular physical activity, including activities to reduce sitting time and to increase aerobic and resistance exercise.
• Cardiac rehabilitation for eligible patients provides significant cardiovascular benefits, including decreased morbidity and mortality.
• Electronic cigarettes increase the odds of successful smoking cessation, but they are not recommended as first-line therapy, owing to the lack of long-term safety data and risks associated with sustained use.

Living document

The co-authors of a related editorial note that “CCD as defined in the 2023 guideline includes patients who may or may not have classic signs and symptoms of CAD.

“The 2023 guideline reflects this heterogeneity by including patients stabilized after acute coronary syndrome hospitalization, those with ischemic cardiomyopathy, stable angina or equivalent with or without a positive imaging test, vasospasm or microvascular disease, and positive noninvasive screening test leading to a clinician diagnosis of CAD,” write Sunil V. Rao, MD, with NYU Langone Health System, and co-authors.

“The focus of the guideline is on extending life and improving quality of life for CCD patients, taking into account patient priorities and the importance of equitable care. There is emphasis on shared decision-making that involves the patient’s preferences and values when considering treatment options,” they point out.

“Importantly, the guidelines exist to provide guidance and are meant to complement, not supplant, clinical judgment. As the evidence for the management of CCD continues to evolve, the guidelines will need to be a ‘living document’ to ensure that clinicians and patients can achieve their shared therapeutic goals of reducing mortality and improving quality of life,” they add.

The 2023 guideline on management of patients with CCD was developed in collaboration with and was endorsed by the American College of Clinical Pharmacy, the American Society for Preventive Cardiology, the National Lipid Association, and the Preventive Cardiovascular Nurses Association. It has been endorsed by the Society for Cardiovascular Angiography and Interventions.

The research had no commercial funding.

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

The latest clinical practice guideline for managing patients with chronic coronary disease (CCD) takes an evidence-based and patient-centered approach to care and includes key updates on revascularization, beta-blocker use, and routine functional and anatomic testing.

Developed by the American Heart Association, the American College of Cardiology, and other specialty societies, the 2023 guideline both updates and consolidates ACC/AHA guidelines previously published in 2012 and 2014 for the management of patients with stable ischemic heart disease.

It was published online in Circulation and the Journal of the American College of Cardiology .

Among the key recommendations were the following.

• Long-term beta-blocker therapy is no longer recommended for improving outcomes for patients with CCD in the absence of myocardial infarction within the past year, left ventricular ejection fraction (LVEF) less than or equal to 50%, or another primary indication for beta-blocker therapy. Either a calcium channel blocker or a beta-blocker is recommended as first-line antianginal therapy.
• Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are recommended for select groups of patients with CCD, including individuals without diabetes, to improve outcomes.
• Statins remain first-line therapy for lipid lowering for patients with CCD. Several adjunctive therapies, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, or bempedoic acid, may be used in select populations, although clinical outcomes data are not yet available for novel agents such as inclisiran and bempedoic acid.
• Shorter durations of dual antiplatelet therapy are safe and effective in many circumstances, particularly when the risk of bleeding is high and the ischemic risk is not high.
• The use of nonprescription or dietary supplements, including fish oil and omega-3 fatty acids or vitamins, is not recommended for patients with CCD, given the lack of benefit in reducing cardiovascular events.
• Revascularization is recommended in two scenarios: (1) for patients with lifestyle-limiting angina despite guideline-directed medical therapy and with coronary stenoses amenable to revascularization, with the goal of improving symptoms; and (2) for patients with significant left main disease or multivessel disease with severe LV dysfunction (LVEF ≤ 35%), for whom coronary artery bypass grafting plus medical therapy is recommended over medical therapy alone, with the goal of improving survival.
• Routine periodic anatomic or ischemic testing in the absence of a change in clinical or functional status is not recommended for risk stratification or to guide therapeutic decision-making for patients with CCD.
• Nondrug therapies, including healthy dietary habits and exercise, are recommended for all patients with CCD. When possible, patients should participate in regular physical activity, including activities to reduce sitting time and to increase aerobic and resistance exercise.
• Cardiac rehabilitation for eligible patients provides significant cardiovascular benefits, including decreased morbidity and mortality.
• Electronic cigarettes increase the odds of successful smoking cessation, but they are not recommended as first-line therapy, owing to the lack of long-term safety data and risks associated with sustained use.

Living document

The co-authors of a related editorial note that “CCD as defined in the 2023 guideline includes patients who may or may not have classic signs and symptoms of CAD.

“The 2023 guideline reflects this heterogeneity by including patients stabilized after acute coronary syndrome hospitalization, those with ischemic cardiomyopathy, stable angina or equivalent with or without a positive imaging test, vasospasm or microvascular disease, and positive noninvasive screening test leading to a clinician diagnosis of CAD,” write Sunil V. Rao, MD, with NYU Langone Health System, and co-authors.

“The focus of the guideline is on extending life and improving quality of life for CCD patients, taking into account patient priorities and the importance of equitable care. There is emphasis on shared decision-making that involves the patient’s preferences and values when considering treatment options,” they point out.

“Importantly, the guidelines exist to provide guidance and are meant to complement, not supplant, clinical judgment. As the evidence for the management of CCD continues to evolve, the guidelines will need to be a ‘living document’ to ensure that clinicians and patients can achieve their shared therapeutic goals of reducing mortality and improving quality of life,” they add.

The 2023 guideline on management of patients with CCD was developed in collaboration with and was endorsed by the American College of Clinical Pharmacy, the American Society for Preventive Cardiology, the National Lipid Association, and the Preventive Cardiovascular Nurses Association. It has been endorsed by the Society for Cardiovascular Angiography and Interventions.

The research had no commercial funding.

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

The latest clinical practice guideline for managing patients with chronic coronary disease (CCD) takes an evidence-based and patient-centered approach to care and includes key updates on revascularization, beta-blocker use, and routine functional and anatomic testing.

Developed by the American Heart Association, the American College of Cardiology, and other specialty societies, the 2023 guideline both updates and consolidates ACC/AHA guidelines previously published in 2012 and 2014 for the management of patients with stable ischemic heart disease.

It was published online in Circulation and the Journal of the American College of Cardiology .

Among the key recommendations were the following.

• Long-term beta-blocker therapy is no longer recommended for improving outcomes for patients with CCD in the absence of myocardial infarction within the past year, left ventricular ejection fraction (LVEF) less than or equal to 50%, or another primary indication for beta-blocker therapy. Either a calcium channel blocker or a beta-blocker is recommended as first-line antianginal therapy.
• Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are recommended for select groups of patients with CCD, including individuals without diabetes, to improve outcomes.
• Statins remain first-line therapy for lipid lowering for patients with CCD. Several adjunctive therapies, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, inclisiran, or bempedoic acid, may be used in select populations, although clinical outcomes data are not yet available for novel agents such as inclisiran and bempedoic acid.
• Shorter durations of dual antiplatelet therapy are safe and effective in many circumstances, particularly when the risk of bleeding is high and the ischemic risk is not high.
• The use of nonprescription or dietary supplements, including fish oil and omega-3 fatty acids or vitamins, is not recommended for patients with CCD, given the lack of benefit in reducing cardiovascular events.
• Revascularization is recommended in two scenarios: (1) for patients with lifestyle-limiting angina despite guideline-directed medical therapy and with coronary stenoses amenable to revascularization, with the goal of improving symptoms; and (2) for patients with significant left main disease or multivessel disease with severe LV dysfunction (LVEF ≤ 35%), for whom coronary artery bypass grafting plus medical therapy is recommended over medical therapy alone, with the goal of improving survival.
• Routine periodic anatomic or ischemic testing in the absence of a change in clinical or functional status is not recommended for risk stratification or to guide therapeutic decision-making for patients with CCD.
• Nondrug therapies, including healthy dietary habits and exercise, are recommended for all patients with CCD. When possible, patients should participate in regular physical activity, including activities to reduce sitting time and to increase aerobic and resistance exercise.
• Cardiac rehabilitation for eligible patients provides significant cardiovascular benefits, including decreased morbidity and mortality.
• Electronic cigarettes increase the odds of successful smoking cessation, but they are not recommended as first-line therapy, owing to the lack of long-term safety data and risks associated with sustained use.

Living document

The co-authors of a related editorial note that “CCD as defined in the 2023 guideline includes patients who may or may not have classic signs and symptoms of CAD.

“The 2023 guideline reflects this heterogeneity by including patients stabilized after acute coronary syndrome hospitalization, those with ischemic cardiomyopathy, stable angina or equivalent with or without a positive imaging test, vasospasm or microvascular disease, and positive noninvasive screening test leading to a clinician diagnosis of CAD,” write Sunil V. Rao, MD, with NYU Langone Health System, and co-authors.

“The focus of the guideline is on extending life and improving quality of life for CCD patients, taking into account patient priorities and the importance of equitable care. There is emphasis on shared decision-making that involves the patient’s preferences and values when considering treatment options,” they point out.

“Importantly, the guidelines exist to provide guidance and are meant to complement, not supplant, clinical judgment. As the evidence for the management of CCD continues to evolve, the guidelines will need to be a ‘living document’ to ensure that clinicians and patients can achieve their shared therapeutic goals of reducing mortality and improving quality of life,” they add.

The 2023 guideline on management of patients with CCD was developed in collaboration with and was endorsed by the American College of Clinical Pharmacy, the American Society for Preventive Cardiology, the National Lipid Association, and the Preventive Cardiovascular Nurses Association. It has been endorsed by the Society for Cardiovascular Angiography and Interventions.

The research had no commercial funding.

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

Questions about omega-3 fatty acid supplements come up often in the atrial fibrillation (AFib) clinic.

The story begins with the simple observation that populations who eat lots of oily fish have fewer coronary events. This correlation provoked great interest in concentrating fish oils in pill form and studying their use to promote health.

A small post hoc study from a group in Norway stimulated me to review what we do and don’t know about fish pills, as I call them in clinic.
 

OMENI secondary analysis

Peder Myhre, MD, and colleagues recently published a secondary analysis of the OMENI trial looking at both the risk and possible causes of AFib in the omega-3 group.

The OMENI trial randomly assigned slightly more than 1,000 older patients (mean age, 75 years) post–myocardial infarction to either 1.8 g/d of fish oil supplements versus placebo for 2 years. The supplements comprised 930 mg of eicosapentaenoic acid (EPA) and 660 mg of docosahexaenoic acid (DHA). The main trial reported no difference in a composite primary endpoint of MI, revascularization, stroke, death, or hospitalization for heart failure.

The secondary analysis explored the 75% of patients in the main trial who had no history of AFib. It looked at how many in each group developed either true clinical AFib or what the authors called micro-AFib, defined as short bursts of irregular atrial activity lasting seconds.

The sub-analysis had three main findings: Patients in the supplement arm had a 90% higher rate of AFib or micro-AFib, compared with patients on placebo, EPA had the strongest effect on the association, and there was a graded risk for AFib with increasing serum EPA levels.  

The authors raised the possibility that more micro-AFib might be a possible mediator of AFib risk.
 

Trials of low-dose EPA and DHA

First, the low-dose trials. In the ASCEND trial from 2018, more than 15,000 patients with diabetes were randomly assigned to either 1 g of omega-3 fatty acids (460-mg EPA and 380-mg DHA) or mineral oil.

The trial was neutral. After 7.4 years, the primary endpoint of MI, stroke, transient ischemic attack, or cardiovascular death occurred in 8.9% of the supplement group versus 9.2% of the placebo arm.The incidence of AFib was higher in the omega-3 group but did not reach statistical significance (2.1% vs. 1.7% for placebo; hazard ratio, 1.23; 95% confidence interval, 0.98-1.54).

Another neutral CV trial, VITAL, specifically studied the effects of marine omega-3 pills (460-mg EPA and 380-mg DHA) in older adults without heart disease, cancer, or AFib. After slightly more than 5 years, AFib occurred at a similar rate in the active arm and placebo arms (3.7% vs. 3.4% for placebo; HR, 1.09; 95% CI, 0.96-1.24; P = .19)
 

Trials of very high-dose marine omega-3s

Next came trials of higher doses in higher-risk populations.

In 2020, JAMA published the STRENGTH trial, which compared 4 g/d of a carboxylic acid formulation of EPA and DHA with a corn oil placebo in more than 13,000 patients who either had established atherosclerotic CV disease (ASCVD) or were at high risk for ASCVD.

The trial was terminated early because of futility and a signal of increased AFib risk in the supplement arm.

Nearly the same number of patients in the supplement versus placebo arm experienced a primary composite endpoint of major adverse cardiac events: 12.0% versus 12.2%, respectively.

AFib was a tertiary endpoint in this trial. An increase in investigator-reported new-onset AFib was observed in the omega-3 group: 2.2% vs. 1.3% for corn oil (HR, 1.69; 95% CI, 1.29-2.21; nominal P < .001).

The REDUCE-IT trial randomly assigned more than 8,000 patients who had ASCVD or diabetes and high ASCVD risk and elevated triglyceride levels to either 4 g of icosapent ethyl daily, a concentrated form of EPA, or a mineral oil placebo.

After nearly 5 years, there was a 4.8% absolute risk reduction in the primary endpoint of CV death, MI, stroke, revascularization, or unstable angina with icosapent ethyl. An increase in atherogenic biomarkers in the mineral oil placebo complicated interpretation of this trial.

Hospitalization for AFib or flutter occurred in 3.1% of the active arm versus 2.1% of the mineral oil group (P = .004).
 

Meta-analysis of marine omega-3 supplement trials

In 2021, Baris Gencer and colleagues performed a meta-analysis of these five trials plus 2 more (GISSI-HF and RP) looking specifically at risk for AFib. Their final analysis included more than 81,000 patients followed for nearly 5 years.

Omega 3 fatty acid supplements associated with a 25% increase in the risk for AFib (HR, 1.25; 95% CI, 1.07-1.46P =.013). Exploring further, they noted a dose-dependent relationship. Most of the increased risk occurred in trials that tested greater than 1 g/d.
 

Summary

When faced with surprise findings, I like to think things through.

First about plausibility. Omega-3 fatty acids clearly exert electrophysiologic effects on cardiac cells, an increase in AFib risk is plausible. The exact underlying mechanism may be unknown, but exact mechanisms are less important than actual clinical effects (see sodium-glucose cotransporter 2 inhibitors).

What about causality? Factors supporting causality include plausibility, consistency of increased AFib risk in multiple studies, and a dose-response relationship.

I see multiple clinical implications of this observation.

The first is the power of the randomized trial to inform practice. If we relied only on observational evidence, we might have assumed that since high fish consumption in populations associated with lower rates of cardiac events, fish oil supplementation would also reduce cardiac events. Other than the outlier trial, REDUCE-IT, with its mineral oil placebo, the preponderance of the randomized controlled trial evidence does not support fish oils for the reduction of CV events.

Randomized controlled trials also exposed the AFib risk. This would have been difficult to sort out in nonrandom observational studies.

Another underappreciated lesson is the notion that drugs, including supplements, can have off-target effects.

Consider the case of statin drugs. It is widely assumed that statins reduce cardiac events by lowering low-density lipoprotein cholesterol (LDL-C). Yet, statins became a mainstay not because of LDL-C lowering but because multiple trials found that this class of drugs reduced cardiac events without increasing adverse effects.

Omega-3 fatty acids reduce triglyceride levels, but this is not enough to adopt the use of these pills. The lack of consistent reduction in CV events and the off-target signal of AFib risk argue against routine use of fish-oil pills.

I will close with uncertainty. Though there is plausibility and multiple reasons to infer causality of marine omega-3s in increasing AFib risk, the effect size remains unknown.

In an editorial accompanying the recent meta-analysis, epidemiologist Michelle Samuel, MPH, PhD, and electrophysiologist Stanley Nattel, MD, cautioned readers on a technical but important point. It concerns the matter of competing risks, such as death, in the analysis of AFib risk, meaning that patients who died may have developed AFib had they lived. They provide a detailed explanation in the open access article, but the take-home is that the exact effect size is difficult to quantify without patient-level original data.

No matter. I find the signal of increased AFib risk an important one to use at the bedside.

Intermittent AFib has an unpredictable natural history. It often resolves as mysteriously as it arises. When patients take fish-oil supplements, I cite these studies, note the lack of CV protection, then I recommend stopping the pills.

This allows for one of the most important interventions in AFib care: time.

Dr. Mandrola is a clinical electrophysiologist with Baptist Medical Associates, Louisville, Ky. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Questions about omega-3 fatty acid supplements come up often in the atrial fibrillation (AFib) clinic.

The story begins with the simple observation that populations who eat lots of oily fish have fewer coronary events. This correlation provoked great interest in concentrating fish oils in pill form and studying their use to promote health.

A small post hoc study from a group in Norway stimulated me to review what we do and don’t know about fish pills, as I call them in clinic.
 

OMENI secondary analysis

Peder Myhre, MD, and colleagues recently published a secondary analysis of the OMENI trial looking at both the risk and possible causes of AFib in the omega-3 group.

The OMENI trial randomly assigned slightly more than 1,000 older patients (mean age, 75 years) post–myocardial infarction to either 1.8 g/d of fish oil supplements versus placebo for 2 years. The supplements comprised 930 mg of eicosapentaenoic acid (EPA) and 660 mg of docosahexaenoic acid (DHA). The main trial reported no difference in a composite primary endpoint of MI, revascularization, stroke, death, or hospitalization for heart failure.

The secondary analysis explored the 75% of patients in the main trial who had no history of AFib. It looked at how many in each group developed either true clinical AFib or what the authors called micro-AFib, defined as short bursts of irregular atrial activity lasting seconds.

The sub-analysis had three main findings: Patients in the supplement arm had a 90% higher rate of AFib or micro-AFib, compared with patients on placebo, EPA had the strongest effect on the association, and there was a graded risk for AFib with increasing serum EPA levels.  

The authors raised the possibility that more micro-AFib might be a possible mediator of AFib risk.
 

Trials of low-dose EPA and DHA

First, the low-dose trials. In the ASCEND trial from 2018, more than 15,000 patients with diabetes were randomly assigned to either 1 g of omega-3 fatty acids (460-mg EPA and 380-mg DHA) or mineral oil.

The trial was neutral. After 7.4 years, the primary endpoint of MI, stroke, transient ischemic attack, or cardiovascular death occurred in 8.9% of the supplement group versus 9.2% of the placebo arm.The incidence of AFib was higher in the omega-3 group but did not reach statistical significance (2.1% vs. 1.7% for placebo; hazard ratio, 1.23; 95% confidence interval, 0.98-1.54).

Another neutral CV trial, VITAL, specifically studied the effects of marine omega-3 pills (460-mg EPA and 380-mg DHA) in older adults without heart disease, cancer, or AFib. After slightly more than 5 years, AFib occurred at a similar rate in the active arm and placebo arms (3.7% vs. 3.4% for placebo; HR, 1.09; 95% CI, 0.96-1.24; P = .19)
 

Trials of very high-dose marine omega-3s

Next came trials of higher doses in higher-risk populations.

In 2020, JAMA published the STRENGTH trial, which compared 4 g/d of a carboxylic acid formulation of EPA and DHA with a corn oil placebo in more than 13,000 patients who either had established atherosclerotic CV disease (ASCVD) or were at high risk for ASCVD.

The trial was terminated early because of futility and a signal of increased AFib risk in the supplement arm.

Nearly the same number of patients in the supplement versus placebo arm experienced a primary composite endpoint of major adverse cardiac events: 12.0% versus 12.2%, respectively.

AFib was a tertiary endpoint in this trial. An increase in investigator-reported new-onset AFib was observed in the omega-3 group: 2.2% vs. 1.3% for corn oil (HR, 1.69; 95% CI, 1.29-2.21; nominal P < .001).

The REDUCE-IT trial randomly assigned more than 8,000 patients who had ASCVD or diabetes and high ASCVD risk and elevated triglyceride levels to either 4 g of icosapent ethyl daily, a concentrated form of EPA, or a mineral oil placebo.

After nearly 5 years, there was a 4.8% absolute risk reduction in the primary endpoint of CV death, MI, stroke, revascularization, or unstable angina with icosapent ethyl. An increase in atherogenic biomarkers in the mineral oil placebo complicated interpretation of this trial.

Hospitalization for AFib or flutter occurred in 3.1% of the active arm versus 2.1% of the mineral oil group (P = .004).
 

Meta-analysis of marine omega-3 supplement trials

In 2021, Baris Gencer and colleagues performed a meta-analysis of these five trials plus 2 more (GISSI-HF and RP) looking specifically at risk for AFib. Their final analysis included more than 81,000 patients followed for nearly 5 years.

Omega 3 fatty acid supplements associated with a 25% increase in the risk for AFib (HR, 1.25; 95% CI, 1.07-1.46P =.013). Exploring further, they noted a dose-dependent relationship. Most of the increased risk occurred in trials that tested greater than 1 g/d.
 

Summary

When faced with surprise findings, I like to think things through.

First about plausibility. Omega-3 fatty acids clearly exert electrophysiologic effects on cardiac cells, an increase in AFib risk is plausible. The exact underlying mechanism may be unknown, but exact mechanisms are less important than actual clinical effects (see sodium-glucose cotransporter 2 inhibitors).

What about causality? Factors supporting causality include plausibility, consistency of increased AFib risk in multiple studies, and a dose-response relationship.

I see multiple clinical implications of this observation.

The first is the power of the randomized trial to inform practice. If we relied only on observational evidence, we might have assumed that since high fish consumption in populations associated with lower rates of cardiac events, fish oil supplementation would also reduce cardiac events. Other than the outlier trial, REDUCE-IT, with its mineral oil placebo, the preponderance of the randomized controlled trial evidence does not support fish oils for the reduction of CV events.

Randomized controlled trials also exposed the AFib risk. This would have been difficult to sort out in nonrandom observational studies.

Another underappreciated lesson is the notion that drugs, including supplements, can have off-target effects.

Consider the case of statin drugs. It is widely assumed that statins reduce cardiac events by lowering low-density lipoprotein cholesterol (LDL-C). Yet, statins became a mainstay not because of LDL-C lowering but because multiple trials found that this class of drugs reduced cardiac events without increasing adverse effects.

Omega-3 fatty acids reduce triglyceride levels, but this is not enough to adopt the use of these pills. The lack of consistent reduction in CV events and the off-target signal of AFib risk argue against routine use of fish-oil pills.

I will close with uncertainty. Though there is plausibility and multiple reasons to infer causality of marine omega-3s in increasing AFib risk, the effect size remains unknown.

In an editorial accompanying the recent meta-analysis, epidemiologist Michelle Samuel, MPH, PhD, and electrophysiologist Stanley Nattel, MD, cautioned readers on a technical but important point. It concerns the matter of competing risks, such as death, in the analysis of AFib risk, meaning that patients who died may have developed AFib had they lived. They provide a detailed explanation in the open access article, but the take-home is that the exact effect size is difficult to quantify without patient-level original data.

No matter. I find the signal of increased AFib risk an important one to use at the bedside.

Intermittent AFib has an unpredictable natural history. It often resolves as mysteriously as it arises. When patients take fish-oil supplements, I cite these studies, note the lack of CV protection, then I recommend stopping the pills.

This allows for one of the most important interventions in AFib care: time.

Dr. Mandrola is a clinical electrophysiologist with Baptist Medical Associates, Louisville, Ky. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Questions about omega-3 fatty acid supplements come up often in the atrial fibrillation (AFib) clinic.

The story begins with the simple observation that populations who eat lots of oily fish have fewer coronary events. This correlation provoked great interest in concentrating fish oils in pill form and studying their use to promote health.

A small post hoc study from a group in Norway stimulated me to review what we do and don’t know about fish pills, as I call them in clinic.
 

OMENI secondary analysis

Peder Myhre, MD, and colleagues recently published a secondary analysis of the OMENI trial looking at both the risk and possible causes of AFib in the omega-3 group.

The OMENI trial randomly assigned slightly more than 1,000 older patients (mean age, 75 years) post–myocardial infarction to either 1.8 g/d of fish oil supplements versus placebo for 2 years. The supplements comprised 930 mg of eicosapentaenoic acid (EPA) and 660 mg of docosahexaenoic acid (DHA). The main trial reported no difference in a composite primary endpoint of MI, revascularization, stroke, death, or hospitalization for heart failure.

The secondary analysis explored the 75% of patients in the main trial who had no history of AFib. It looked at how many in each group developed either true clinical AFib or what the authors called micro-AFib, defined as short bursts of irregular atrial activity lasting seconds.

The sub-analysis had three main findings: Patients in the supplement arm had a 90% higher rate of AFib or micro-AFib, compared with patients on placebo, EPA had the strongest effect on the association, and there was a graded risk for AFib with increasing serum EPA levels.  

The authors raised the possibility that more micro-AFib might be a possible mediator of AFib risk.
 

Trials of low-dose EPA and DHA

First, the low-dose trials. In the ASCEND trial from 2018, more than 15,000 patients with diabetes were randomly assigned to either 1 g of omega-3 fatty acids (460-mg EPA and 380-mg DHA) or mineral oil.

The trial was neutral. After 7.4 years, the primary endpoint of MI, stroke, transient ischemic attack, or cardiovascular death occurred in 8.9% of the supplement group versus 9.2% of the placebo arm.The incidence of AFib was higher in the omega-3 group but did not reach statistical significance (2.1% vs. 1.7% for placebo; hazard ratio, 1.23; 95% confidence interval, 0.98-1.54).

Another neutral CV trial, VITAL, specifically studied the effects of marine omega-3 pills (460-mg EPA and 380-mg DHA) in older adults without heart disease, cancer, or AFib. After slightly more than 5 years, AFib occurred at a similar rate in the active arm and placebo arms (3.7% vs. 3.4% for placebo; HR, 1.09; 95% CI, 0.96-1.24; P = .19)
 

Trials of very high-dose marine omega-3s

Next came trials of higher doses in higher-risk populations.

In 2020, JAMA published the STRENGTH trial, which compared 4 g/d of a carboxylic acid formulation of EPA and DHA with a corn oil placebo in more than 13,000 patients who either had established atherosclerotic CV disease (ASCVD) or were at high risk for ASCVD.

The trial was terminated early because of futility and a signal of increased AFib risk in the supplement arm.

Nearly the same number of patients in the supplement versus placebo arm experienced a primary composite endpoint of major adverse cardiac events: 12.0% versus 12.2%, respectively.

AFib was a tertiary endpoint in this trial. An increase in investigator-reported new-onset AFib was observed in the omega-3 group: 2.2% vs. 1.3% for corn oil (HR, 1.69; 95% CI, 1.29-2.21; nominal P < .001).

The REDUCE-IT trial randomly assigned more than 8,000 patients who had ASCVD or diabetes and high ASCVD risk and elevated triglyceride levels to either 4 g of icosapent ethyl daily, a concentrated form of EPA, or a mineral oil placebo.

After nearly 5 years, there was a 4.8% absolute risk reduction in the primary endpoint of CV death, MI, stroke, revascularization, or unstable angina with icosapent ethyl. An increase in atherogenic biomarkers in the mineral oil placebo complicated interpretation of this trial.

Hospitalization for AFib or flutter occurred in 3.1% of the active arm versus 2.1% of the mineral oil group (P = .004).
 

Meta-analysis of marine omega-3 supplement trials

In 2021, Baris Gencer and colleagues performed a meta-analysis of these five trials plus 2 more (GISSI-HF and RP) looking specifically at risk for AFib. Their final analysis included more than 81,000 patients followed for nearly 5 years.

Omega 3 fatty acid supplements associated with a 25% increase in the risk for AFib (HR, 1.25; 95% CI, 1.07-1.46P =.013). Exploring further, they noted a dose-dependent relationship. Most of the increased risk occurred in trials that tested greater than 1 g/d.
 

Summary

When faced with surprise findings, I like to think things through.

First about plausibility. Omega-3 fatty acids clearly exert electrophysiologic effects on cardiac cells, an increase in AFib risk is plausible. The exact underlying mechanism may be unknown, but exact mechanisms are less important than actual clinical effects (see sodium-glucose cotransporter 2 inhibitors).

What about causality? Factors supporting causality include plausibility, consistency of increased AFib risk in multiple studies, and a dose-response relationship.

I see multiple clinical implications of this observation.

The first is the power of the randomized trial to inform practice. If we relied only on observational evidence, we might have assumed that since high fish consumption in populations associated with lower rates of cardiac events, fish oil supplementation would also reduce cardiac events. Other than the outlier trial, REDUCE-IT, with its mineral oil placebo, the preponderance of the randomized controlled trial evidence does not support fish oils for the reduction of CV events.

Randomized controlled trials also exposed the AFib risk. This would have been difficult to sort out in nonrandom observational studies.

Another underappreciated lesson is the notion that drugs, including supplements, can have off-target effects.

Consider the case of statin drugs. It is widely assumed that statins reduce cardiac events by lowering low-density lipoprotein cholesterol (LDL-C). Yet, statins became a mainstay not because of LDL-C lowering but because multiple trials found that this class of drugs reduced cardiac events without increasing adverse effects.

Omega-3 fatty acids reduce triglyceride levels, but this is not enough to adopt the use of these pills. The lack of consistent reduction in CV events and the off-target signal of AFib risk argue against routine use of fish-oil pills.

I will close with uncertainty. Though there is plausibility and multiple reasons to infer causality of marine omega-3s in increasing AFib risk, the effect size remains unknown.

In an editorial accompanying the recent meta-analysis, epidemiologist Michelle Samuel, MPH, PhD, and electrophysiologist Stanley Nattel, MD, cautioned readers on a technical but important point. It concerns the matter of competing risks, such as death, in the analysis of AFib risk, meaning that patients who died may have developed AFib had they lived. They provide a detailed explanation in the open access article, but the take-home is that the exact effect size is difficult to quantify without patient-level original data.

No matter. I find the signal of increased AFib risk an important one to use at the bedside.

Intermittent AFib has an unpredictable natural history. It often resolves as mysteriously as it arises. When patients take fish-oil supplements, I cite these studies, note the lack of CV protection, then I recommend stopping the pills.

This allows for one of the most important interventions in AFib care: time.

Dr. Mandrola is a clinical electrophysiologist with Baptist Medical Associates, Louisville, Ky. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Drinking sugar-laden beverages on a regular basis may increase the risk for liver cancer and death from chronic liver disease, new research suggests.

The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.

Lori Martin/Fotolia.com

“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”

The new study was published online in JAMA.

About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.

Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.

In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”

To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.

Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.

Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.

Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).

Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).

The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.

Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.

“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.

The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”

Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”

In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.

“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.

However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”

It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”

Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”

In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.

In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”

“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”

The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.

A version of this article appeared on Medscape.com.

Drinking sugar-laden beverages on a regular basis may increase the risk for liver cancer and death from chronic liver disease, new research suggests.

The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.

Lori Martin/Fotolia.com

“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”

The new study was published online in JAMA.

About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.

Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.

In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”

To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.

Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.

Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.

Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).

Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).

The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.

Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.

“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.

The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”

Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”

In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.

“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.

However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”

It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”

Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”

In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.

In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”

“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”

The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.

A version of this article appeared on Medscape.com.

Drinking sugar-laden beverages on a regular basis may increase the risk for liver cancer and death from chronic liver disease, new research suggests.

The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.

Lori Martin/Fotolia.com

“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.

When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”

The new study was published online in JAMA.

About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.

Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.

In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”

To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.

Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.

Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.

Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).

Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).

The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.

Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.

“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.

The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”

Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”

In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.

“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.

However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”

It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”

Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”

In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.

In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”

“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”

The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.

A version of this article appeared on Medscape.com.

Isometric exercise training emerged as the most effective mode to reduce blood pressure in a systematic review and meta-analysis of 270 randomized trials with close to 16,000 participants.

The findings support the development of new exercise guidelines for blood pressure control, the authors said.

Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.

Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.

The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.

“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”

The study was published online in the British Journal of Sports Medicine.
 

All modes effective

The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.

All protocols were then stratified as AET, RT, CT, HIIT or IET.

As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.

Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.

All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.

Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).

In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).

Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.

Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.

The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.

Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
 

Guideline changing?

“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”

In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.

In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”

“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.

That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”

The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.

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

Isometric exercise training emerged as the most effective mode to reduce blood pressure in a systematic review and meta-analysis of 270 randomized trials with close to 16,000 participants.

The findings support the development of new exercise guidelines for blood pressure control, the authors said.

Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.

Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.

The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.

“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”

The study was published online in the British Journal of Sports Medicine.
 

All modes effective

The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.

All protocols were then stratified as AET, RT, CT, HIIT or IET.

As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.

Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.

All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.

Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).

In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).

Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.

Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.

The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.

Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
 

Guideline changing?

“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”

In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.

In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”

“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.

That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”

The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.

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

Isometric exercise training emerged as the most effective mode to reduce blood pressure in a systematic review and meta-analysis of 270 randomized trials with close to 16,000 participants.

The findings support the development of new exercise guidelines for blood pressure control, the authors said.

Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.

Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.

The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.

“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”

The study was published online in the British Journal of Sports Medicine.
 

All modes effective

The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.

All protocols were then stratified as AET, RT, CT, HIIT or IET.

As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.

Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.

All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.

Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).

In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).

Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.

Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.

The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.

Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
 

Guideline changing?

“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”

In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.

In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”

“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.

That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”

The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.

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

A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).

This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.

The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.

The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m² – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.

The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.

After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
 

Weight losses never before seen

“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.

A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.

“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.

The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.

The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.

Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
 

Triple agonist has added effect on liver fat clearance

The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.

A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).

That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.

“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m².

Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.

The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.

The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.

Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.

The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.

The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
 

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

A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).

This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.

The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.

The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m² – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.

The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.

After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
 

Weight losses never before seen

“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.

A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.

“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.

The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.

The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.

Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
 

Triple agonist has added effect on liver fat clearance

The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.

A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).

That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.

“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m².

Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.

The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.

The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.

Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.

The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.

The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
 

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

A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).

This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.

The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.

The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m² – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.

The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.

After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
 

Weight losses never before seen

“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.

A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.

“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.

The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.

The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.

Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
 

Triple agonist has added effect on liver fat clearance

The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.

A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).

That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.

“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.

The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m².

Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.

The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.

The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.

Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.

The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.

The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
 

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