Clinician Reviews

The only HIV vaccine nearing the completion of testing trials is not effective at preventing HIV, officials announced Wednesday.

The vaccine had been in development since 2019 and was given to 3,900 study participants through October 2022, but data shows it does not protect against HIV compared with a placebo, according to developer Janssen Pharmaceutical.

Experts estimate the failure means there won’t be another potential vaccine on the horizon for 3 to 5 years, the New York Times reported.

“It’s obviously disappointing,” Anthony Fauci, MD, former head of the National Institute of Allergy and Infectious Diseases, told MSNBC, noting that other areas of HIV treatment research are promising. “I don’t think that people should give up on the field of the HIV vaccine.”

No safety issues had been identified with the vaccine during the trial, which studied the experimental treatment in men who have sex with men or with transgender people.

There is no cure for HIV, but disease progression can be managed with existing treatments. HIV attacks the body’s immune system and destroys white blood cells, increasing the risk of other infections. More than 1.5 million people worldwide were infected with HIV in 2021 and 38.4 million people are living with the virus, according to UNAIDS.

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

The only HIV vaccine nearing the completion of testing trials is not effective at preventing HIV, officials announced Wednesday.

The vaccine had been in development since 2019 and was given to 3,900 study participants through October 2022, but data shows it does not protect against HIV compared with a placebo, according to developer Janssen Pharmaceutical.

Experts estimate the failure means there won’t be another potential vaccine on the horizon for 3 to 5 years, the New York Times reported.

“It’s obviously disappointing,” Anthony Fauci, MD, former head of the National Institute of Allergy and Infectious Diseases, told MSNBC, noting that other areas of HIV treatment research are promising. “I don’t think that people should give up on the field of the HIV vaccine.”

No safety issues had been identified with the vaccine during the trial, which studied the experimental treatment in men who have sex with men or with transgender people.

There is no cure for HIV, but disease progression can be managed with existing treatments. HIV attacks the body’s immune system and destroys white blood cells, increasing the risk of other infections. More than 1.5 million people worldwide were infected with HIV in 2021 and 38.4 million people are living with the virus, according to UNAIDS.

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

The only HIV vaccine nearing the completion of testing trials is not effective at preventing HIV, officials announced Wednesday.

The vaccine had been in development since 2019 and was given to 3,900 study participants through October 2022, but data shows it does not protect against HIV compared with a placebo, according to developer Janssen Pharmaceutical.

Experts estimate the failure means there won’t be another potential vaccine on the horizon for 3 to 5 years, the New York Times reported.

“It’s obviously disappointing,” Anthony Fauci, MD, former head of the National Institute of Allergy and Infectious Diseases, told MSNBC, noting that other areas of HIV treatment research are promising. “I don’t think that people should give up on the field of the HIV vaccine.”

No safety issues had been identified with the vaccine during the trial, which studied the experimental treatment in men who have sex with men or with transgender people.

There is no cure for HIV, but disease progression can be managed with existing treatments. HIV attacks the body’s immune system and destroys white blood cells, increasing the risk of other infections. More than 1.5 million people worldwide were infected with HIV in 2021 and 38.4 million people are living with the virus, according to UNAIDS.

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

Eating in response to stress – known as emotional eating – was significantly associated with several markers of long-term cardiovascular damage, based on data from 1,109 individuals.

“We know diet plays a huge role in cardiovascular disease, but we have focused a lot of work on what you eat, not on what makes you eat” – the current study did exactly that, Martha Gulati, MD, who wasn’t involved in the study, said in an interview.

Courtesy Cedars-Sinai

“Emotional eaters consume food to satisfy their brains rather than their stomachs,” study investigator Nicolas Girerd, MD, of the National Institute of Health and Medical Research (INSERM) and a cardiologist at the University Hospital of Nancy (France), wrote in a press release accompanying the study.

Diet plays a role in the development of cardiovascular disease (CVD), but the impact of eating behavior on long-term cardiovascular health remains unclear, wrote Dr. Girerd and colleagues. Previous research has yielded three common psychological dimensions for eating behavior: emotional eating, restrained eating, and external eating.

Both emotional eating and restrained eating have been linked to cardiovascular disease risk, the researchers noted. “Because of previous findings, we hypothesized that [emotional and/or restrained dimensions of eating behavior] are positively associated with cardiovascular damages, as well as with CV risk factors, such as metabolic syndrome,” they wrote.

In a study published in the European Journal of Preventive Cardiology, the researchers reviewed data from 916 adults and 193 adolescents who were participants in the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux), a longitudinal familial cohort in France. Cardiovascular data were collected at four medical visits as part of a full clinical examination between 1993 and 2016, with one visit every 5-10 years. Roughly one-third (31.0%) of the adults were overweight, 7.9% were obese, and 2.7% were underweight. The median age of the adults at the second visit was 44.7 years; the median age of the adolescent group was 15.2 years.

The primary outcome of cardiovascular damage was measured at the fourth visit. Eating behavior was assessed during the second visit using the Dutch Eating Behaviour Questionnaire (DEBQ), and participants were identified as emotional eaters, restrained eaters, or external eaters.

Among the adults, emotional eating was associated with a 38% increased risk of diastolic dysfunction (odds ratio, 1.38; P = .02), over an average follow-up of 13 years, and this association was mediated by stress in 32% of cases. Emotional eating also was positively linked with a higher carotid-femoral pulse-wave velocity (cfPWV-beta), indicative of increased arterial stiffness. However, none of the three dimensions of eating behavior was associated with cardiovascular damage among the adolescents. In addition, none of the eating-behavior dimensions was tied to metabolic syndrome in the adult group (this association was not measured in the adolescents).

Energy intake had no apparent impact on any associations between eating behavior and CVD measures, Dr. Girerd said in the press release. “We might expect that emotional eaters would consume high-calorie foods, which would in turn lead to cardiovascular problems, but this was not the case. One explanation is that we measured average calorie intake and emotional eaters may binge when stressed and then eat less at other times,” and that the resulting “yo-yo” pattern might negatively affect the heart and blood vessels more than stable food intake, he said.

The study findings were limited by several factors, including the observational design that prevented conclusions of causality, the researchers noted. Other limitations included the use of a nonvalidated scale to measure stress, the lack of data on physical activity, and the use of a mainly healthy population in a limited geographic area, which may limit generalizability, they said.

More research is needed in other contexts and larger cohorts, but the results were strengthened by the large study population and the complete data on eating behaviors and detailed health information, they wrote. The results support previous studies and suggest that patients with emotional eating behavior could benefit from emotion regulation skills training, including cognitive, behavioral, psychological, and interpersonal therapies used in other areas, and from pharmacological treatments, the researchers concluded.

The current study offers a unique and important perspective on the relationship between diet and cardiovascular disease, Dr. Gulati, director of preventive cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Examining eating behavior and its relationship with cardiovascular effects in healthy individuals in this prospective way is quite interesting,” said Dr. Gulati, who was not involved in the study.

The researchers examined healthy people at baseline, inquired about their eating habits, and found that emotional eaters “have evidence of cardiovascular changes when compared with the other groups of eaters, after controlling for other risk factors that are associated with cardiovascular disease when following them for 13 years,” said Dr. Gulati, who was recently named Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research at Cedars-Sinai. “This same finding wasn’t seen in adolescents, but this is probably because they are younger, and the effects aren’t seen. That is reassuring, because it means that the more we address eating behaviors, the more likely we are to reduce their effects to the heart,” she noted.

“This study is important because usually, as cardiologists or anyone in medicine, how we assess diet is by assessment of what food people eat; we don’t usually ask about what triggers them to eat,” Dr. Gulati said. “Eating behaviors based on their triggers ultimately affect food choice and food quantity, and help us understand weight changes during a lifetime,” she said.

“I think we don’t have the data to know that an eating behavior would be able to affect cardiac function,” said Dr. Gulati, “but I think we all might hypothesize that emotional eating may be associated with abnormal diastolic function simply through eating high-density food and weight gain.”

The current study did not show a relationship between eating behavior and metabolic syndrome, in contrast with prior studies, Dr. Gulati noted. However, “the authors report that the association between eating behaviors and diastolic dysfunction was mediated through the stress level,” Dr. Gulati said. “It is important to note that this European population was healthy at baseline, and also relatively healthy 13 years later, which makes these findings even more profound.”

Dr. Gulati said that she agrees with the study authors on the need to assess diet and eating behaviors when assessing cardiovascular risk in patient. “Diet assessment as part of prevention is central, but we should ask not only ‘what do you eat,’ but also ‘what makes you eat,’ ” she said.

More research is needed in other populations, Dr. Gulati added. The current study population was healthy at baseline and follow-up. Studies are needed in cohorts in the United States and in the developing world to see how the results might differ; as well as in rural America or in “food deserts” where food choices are limited.

Another research topic is the interplay between eating behaviors and social determinants of health, in terms of their effect on cardiovascular function, Dr. Gulati said, “and it will be valuable to follow this cohort further to see how these eating behaviors and these intermediate measures translate into cardiovascular outcomes.” Future studies should also examine whether the changes in cardiac function are reversible by interventions to modify eating behavior, particularly emotional eating, she said.

Supporters of the study included the Regional University Hospital Center of Nancy, the French Ministry of Solidarity and Health, and a public grant overseen by the French National Research Agency. The researchers had no financial conflicts to disclose.

Dr. Gulati, who serves on the editorial advisory board of MDedge Cardiology, had no financial conflicts to disclose.
 

Eating in response to stress – known as emotional eating – was significantly associated with several markers of long-term cardiovascular damage, based on data from 1,109 individuals.

“We know diet plays a huge role in cardiovascular disease, but we have focused a lot of work on what you eat, not on what makes you eat” – the current study did exactly that, Martha Gulati, MD, who wasn’t involved in the study, said in an interview.

Courtesy Cedars-Sinai

“Emotional eaters consume food to satisfy their brains rather than their stomachs,” study investigator Nicolas Girerd, MD, of the National Institute of Health and Medical Research (INSERM) and a cardiologist at the University Hospital of Nancy (France), wrote in a press release accompanying the study.

Diet plays a role in the development of cardiovascular disease (CVD), but the impact of eating behavior on long-term cardiovascular health remains unclear, wrote Dr. Girerd and colleagues. Previous research has yielded three common psychological dimensions for eating behavior: emotional eating, restrained eating, and external eating.

Both emotional eating and restrained eating have been linked to cardiovascular disease risk, the researchers noted. “Because of previous findings, we hypothesized that [emotional and/or restrained dimensions of eating behavior] are positively associated with cardiovascular damages, as well as with CV risk factors, such as metabolic syndrome,” they wrote.

In a study published in the European Journal of Preventive Cardiology, the researchers reviewed data from 916 adults and 193 adolescents who were participants in the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux), a longitudinal familial cohort in France. Cardiovascular data were collected at four medical visits as part of a full clinical examination between 1993 and 2016, with one visit every 5-10 years. Roughly one-third (31.0%) of the adults were overweight, 7.9% were obese, and 2.7% were underweight. The median age of the adults at the second visit was 44.7 years; the median age of the adolescent group was 15.2 years.

The primary outcome of cardiovascular damage was measured at the fourth visit. Eating behavior was assessed during the second visit using the Dutch Eating Behaviour Questionnaire (DEBQ), and participants were identified as emotional eaters, restrained eaters, or external eaters.

Among the adults, emotional eating was associated with a 38% increased risk of diastolic dysfunction (odds ratio, 1.38; P = .02), over an average follow-up of 13 years, and this association was mediated by stress in 32% of cases. Emotional eating also was positively linked with a higher carotid-femoral pulse-wave velocity (cfPWV-beta), indicative of increased arterial stiffness. However, none of the three dimensions of eating behavior was associated with cardiovascular damage among the adolescents. In addition, none of the eating-behavior dimensions was tied to metabolic syndrome in the adult group (this association was not measured in the adolescents).

Energy intake had no apparent impact on any associations between eating behavior and CVD measures, Dr. Girerd said in the press release. “We might expect that emotional eaters would consume high-calorie foods, which would in turn lead to cardiovascular problems, but this was not the case. One explanation is that we measured average calorie intake and emotional eaters may binge when stressed and then eat less at other times,” and that the resulting “yo-yo” pattern might negatively affect the heart and blood vessels more than stable food intake, he said.

The study findings were limited by several factors, including the observational design that prevented conclusions of causality, the researchers noted. Other limitations included the use of a nonvalidated scale to measure stress, the lack of data on physical activity, and the use of a mainly healthy population in a limited geographic area, which may limit generalizability, they said.

More research is needed in other contexts and larger cohorts, but the results were strengthened by the large study population and the complete data on eating behaviors and detailed health information, they wrote. The results support previous studies and suggest that patients with emotional eating behavior could benefit from emotion regulation skills training, including cognitive, behavioral, psychological, and interpersonal therapies used in other areas, and from pharmacological treatments, the researchers concluded.

The current study offers a unique and important perspective on the relationship between diet and cardiovascular disease, Dr. Gulati, director of preventive cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Examining eating behavior and its relationship with cardiovascular effects in healthy individuals in this prospective way is quite interesting,” said Dr. Gulati, who was not involved in the study.

The researchers examined healthy people at baseline, inquired about their eating habits, and found that emotional eaters “have evidence of cardiovascular changes when compared with the other groups of eaters, after controlling for other risk factors that are associated with cardiovascular disease when following them for 13 years,” said Dr. Gulati, who was recently named Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research at Cedars-Sinai. “This same finding wasn’t seen in adolescents, but this is probably because they are younger, and the effects aren’t seen. That is reassuring, because it means that the more we address eating behaviors, the more likely we are to reduce their effects to the heart,” she noted.

“This study is important because usually, as cardiologists or anyone in medicine, how we assess diet is by assessment of what food people eat; we don’t usually ask about what triggers them to eat,” Dr. Gulati said. “Eating behaviors based on their triggers ultimately affect food choice and food quantity, and help us understand weight changes during a lifetime,” she said.

“I think we don’t have the data to know that an eating behavior would be able to affect cardiac function,” said Dr. Gulati, “but I think we all might hypothesize that emotional eating may be associated with abnormal diastolic function simply through eating high-density food and weight gain.”

The current study did not show a relationship between eating behavior and metabolic syndrome, in contrast with prior studies, Dr. Gulati noted. However, “the authors report that the association between eating behaviors and diastolic dysfunction was mediated through the stress level,” Dr. Gulati said. “It is important to note that this European population was healthy at baseline, and also relatively healthy 13 years later, which makes these findings even more profound.”

Dr. Gulati said that she agrees with the study authors on the need to assess diet and eating behaviors when assessing cardiovascular risk in patient. “Diet assessment as part of prevention is central, but we should ask not only ‘what do you eat,’ but also ‘what makes you eat,’ ” she said.

More research is needed in other populations, Dr. Gulati added. The current study population was healthy at baseline and follow-up. Studies are needed in cohorts in the United States and in the developing world to see how the results might differ; as well as in rural America or in “food deserts” where food choices are limited.

Another research topic is the interplay between eating behaviors and social determinants of health, in terms of their effect on cardiovascular function, Dr. Gulati said, “and it will be valuable to follow this cohort further to see how these eating behaviors and these intermediate measures translate into cardiovascular outcomes.” Future studies should also examine whether the changes in cardiac function are reversible by interventions to modify eating behavior, particularly emotional eating, she said.

Supporters of the study included the Regional University Hospital Center of Nancy, the French Ministry of Solidarity and Health, and a public grant overseen by the French National Research Agency. The researchers had no financial conflicts to disclose.

Dr. Gulati, who serves on the editorial advisory board of MDedge Cardiology, had no financial conflicts to disclose.
 

Eating in response to stress – known as emotional eating – was significantly associated with several markers of long-term cardiovascular damage, based on data from 1,109 individuals.

“We know diet plays a huge role in cardiovascular disease, but we have focused a lot of work on what you eat, not on what makes you eat” – the current study did exactly that, Martha Gulati, MD, who wasn’t involved in the study, said in an interview.

Courtesy Cedars-Sinai

“Emotional eaters consume food to satisfy their brains rather than their stomachs,” study investigator Nicolas Girerd, MD, of the National Institute of Health and Medical Research (INSERM) and a cardiologist at the University Hospital of Nancy (France), wrote in a press release accompanying the study.

Diet plays a role in the development of cardiovascular disease (CVD), but the impact of eating behavior on long-term cardiovascular health remains unclear, wrote Dr. Girerd and colleagues. Previous research has yielded three common psychological dimensions for eating behavior: emotional eating, restrained eating, and external eating.

Both emotional eating and restrained eating have been linked to cardiovascular disease risk, the researchers noted. “Because of previous findings, we hypothesized that [emotional and/or restrained dimensions of eating behavior] are positively associated with cardiovascular damages, as well as with CV risk factors, such as metabolic syndrome,” they wrote.

In a study published in the European Journal of Preventive Cardiology, the researchers reviewed data from 916 adults and 193 adolescents who were participants in the STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux), a longitudinal familial cohort in France. Cardiovascular data were collected at four medical visits as part of a full clinical examination between 1993 and 2016, with one visit every 5-10 years. Roughly one-third (31.0%) of the adults were overweight, 7.9% were obese, and 2.7% were underweight. The median age of the adults at the second visit was 44.7 years; the median age of the adolescent group was 15.2 years.

The primary outcome of cardiovascular damage was measured at the fourth visit. Eating behavior was assessed during the second visit using the Dutch Eating Behaviour Questionnaire (DEBQ), and participants were identified as emotional eaters, restrained eaters, or external eaters.

Among the adults, emotional eating was associated with a 38% increased risk of diastolic dysfunction (odds ratio, 1.38; P = .02), over an average follow-up of 13 years, and this association was mediated by stress in 32% of cases. Emotional eating also was positively linked with a higher carotid-femoral pulse-wave velocity (cfPWV-beta), indicative of increased arterial stiffness. However, none of the three dimensions of eating behavior was associated with cardiovascular damage among the adolescents. In addition, none of the eating-behavior dimensions was tied to metabolic syndrome in the adult group (this association was not measured in the adolescents).

Energy intake had no apparent impact on any associations between eating behavior and CVD measures, Dr. Girerd said in the press release. “We might expect that emotional eaters would consume high-calorie foods, which would in turn lead to cardiovascular problems, but this was not the case. One explanation is that we measured average calorie intake and emotional eaters may binge when stressed and then eat less at other times,” and that the resulting “yo-yo” pattern might negatively affect the heart and blood vessels more than stable food intake, he said.

The study findings were limited by several factors, including the observational design that prevented conclusions of causality, the researchers noted. Other limitations included the use of a nonvalidated scale to measure stress, the lack of data on physical activity, and the use of a mainly healthy population in a limited geographic area, which may limit generalizability, they said.

More research is needed in other contexts and larger cohorts, but the results were strengthened by the large study population and the complete data on eating behaviors and detailed health information, they wrote. The results support previous studies and suggest that patients with emotional eating behavior could benefit from emotion regulation skills training, including cognitive, behavioral, psychological, and interpersonal therapies used in other areas, and from pharmacological treatments, the researchers concluded.

The current study offers a unique and important perspective on the relationship between diet and cardiovascular disease, Dr. Gulati, director of preventive cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center, Los Angeles, told this news organization.

“Examining eating behavior and its relationship with cardiovascular effects in healthy individuals in this prospective way is quite interesting,” said Dr. Gulati, who was not involved in the study.

The researchers examined healthy people at baseline, inquired about their eating habits, and found that emotional eaters “have evidence of cardiovascular changes when compared with the other groups of eaters, after controlling for other risk factors that are associated with cardiovascular disease when following them for 13 years,” said Dr. Gulati, who was recently named Anita Dann Friedman Endowed Chair in Women’s Cardiovascular Medicine and Research at Cedars-Sinai. “This same finding wasn’t seen in adolescents, but this is probably because they are younger, and the effects aren’t seen. That is reassuring, because it means that the more we address eating behaviors, the more likely we are to reduce their effects to the heart,” she noted.

“This study is important because usually, as cardiologists or anyone in medicine, how we assess diet is by assessment of what food people eat; we don’t usually ask about what triggers them to eat,” Dr. Gulati said. “Eating behaviors based on their triggers ultimately affect food choice and food quantity, and help us understand weight changes during a lifetime,” she said.

“I think we don’t have the data to know that an eating behavior would be able to affect cardiac function,” said Dr. Gulati, “but I think we all might hypothesize that emotional eating may be associated with abnormal diastolic function simply through eating high-density food and weight gain.”

The current study did not show a relationship between eating behavior and metabolic syndrome, in contrast with prior studies, Dr. Gulati noted. However, “the authors report that the association between eating behaviors and diastolic dysfunction was mediated through the stress level,” Dr. Gulati said. “It is important to note that this European population was healthy at baseline, and also relatively healthy 13 years later, which makes these findings even more profound.”

Dr. Gulati said that she agrees with the study authors on the need to assess diet and eating behaviors when assessing cardiovascular risk in patient. “Diet assessment as part of prevention is central, but we should ask not only ‘what do you eat,’ but also ‘what makes you eat,’ ” she said.

More research is needed in other populations, Dr. Gulati added. The current study population was healthy at baseline and follow-up. Studies are needed in cohorts in the United States and in the developing world to see how the results might differ; as well as in rural America or in “food deserts” where food choices are limited.

Another research topic is the interplay between eating behaviors and social determinants of health, in terms of their effect on cardiovascular function, Dr. Gulati said, “and it will be valuable to follow this cohort further to see how these eating behaviors and these intermediate measures translate into cardiovascular outcomes.” Future studies should also examine whether the changes in cardiac function are reversible by interventions to modify eating behavior, particularly emotional eating, she said.

Supporters of the study included the Regional University Hospital Center of Nancy, the French Ministry of Solidarity and Health, and a public grant overseen by the French National Research Agency. The researchers had no financial conflicts to disclose.

Dr. Gulati, who serves on the editorial advisory board of MDedge Cardiology, had no financial conflicts to disclose.
 

On Twitter, as in real life, it’s a question on many minds: When should we think about the next COVID-19 vaccine? Or should we?

For some people who have received a two-dose primary series and all the recommended boosters, that could mean a sixth shot since COVID-19 vaccines became available. But is even that enough (or too much)?

At this point, no one knows for sure, but new guidance may be on the docket.

On Jan. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee is meeting. On the agenda is discussion about plans for future vaccinations for COVID-19.The committee, made up of external advisers, evaluates data on vaccines and other products for the agency.

According to the FDA announcement, after the meeting, “the FDA will consider whether to recommend adjustments to the current authorizations and approvals, and the FDA will consider the most efficient and transparent process to use for selection of strains for inclusion in the primary and booster vaccines.”

From there, the CDC will take up the issue and decide on recommendations.

The issue is important, as more than 550 Americans a day are still dying from COVID-19, as of the week ending Jan. 13, the CDC reported. That’s up from 346 a day for the week ending Dec. 28.

Yet, uptake of the newest vaccine, the bivalent booster, has been slow. As of Jan. 11, just 15.9% of the population 5 years and up has gotten it; for those most vulnerable to COVID19 – those 65 and up – the number is just 39%.
 

COVID vaccines, 2023 and beyond

Meanwhile, infectious disease experts have widely differing views on what the vaccination landscape of 2023 and beyond should look like. Among the areas of disagreement are how effective the bivalent vaccine is, which people most need another shot, and what type of vaccine is best.

“I think we probably will need another booster,” says Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, and codirector of the Center for Vaccine Development at Texas Children’s Hospital in Houston. “The question is, what is it going to be? Is it going to be the same bivalent that we just got, or will it be a new bivalent or even a trivalent?” 

The trivalent booster, he suggested, might include something more protective against XBB.1.5.

The bivalent booster gives “broadened immunity” that is improved from the original booster shots, says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape, WebMD’s sister site for health professionals.

In his publication Ground Truths, Dr. Topol on Jan. 11 explained how new data caused him to reverse his previously skeptical view of how the FDA authorized the bivalent vaccine in September without data on how it affected humans at the time.

Paul Offit, MD, director of the Vaccine Education Center and a professor of pediatrics at the Children’s Hospital of Philadelphia, is a member of the FDA advisory committee for vaccines. He still takes a dimmer view of more bivalent booster vaccines, at least as a blanket recommendation. 

While he acknowledges that boosters can help some groups – such as older adults, people with multiple health conditions, and those with compromised immune systems – he opposes a recommendation that’s population-wide.

“People who fall into those three groups do benefit,” he says, “but the recommendation is everyone over 6 months get the bivalent, and what I’m asking is, ‘Where is the data that a healthy 12-year-old boy needs a booster to stay out of the hospital?’ ”
 

Evolving research

“We are trying to understand how to stay one step ahead rather than several steps behind [the virus],“ says Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Among the key questions: How well can a vaccine work against a single subvariant, when no one can say for sure what the next predominant subvariant will be?

Much more research has become available recently about the bivalent vaccine and its effectiveness, Dr. Osterholm says. “The bivalent vaccine is working as well as we could have expected,” he says, especially in high-risk people and in those over age 65. “The challenge we have is, what does that mean going forward?”

In his review, Dr. Topol concludes: “There is now more than ample, highly consistent evidence via lab studies and clinical outcomes to support the bivalent’s benefit over the original booster.”

Among other evidence, he looked at eight studies, including four that used a live virus as part of the research. Six of the eight studies showed the bivalent booster is more effective against the BA.5 variant, compared with the original booster shots. Two others showed no real difference.

“The four live virus studies offer consistent evidence of broadened immunity for the BA.5 vaccine that is improved over the original booster shots,” Dr. Topol wrote. The evidence also found the bivalent antibody response superior against XBB, he wrote.

Dr. Topol also cited CDC data that supports the benefits of the bivalent shot on hospitalization in older adults. During November, hospitalization of adults 65 and above was 2.5 times higher for those vaccinated who did not get the booster, compared to those who got the updated bivalent booster.

Boosters do matter, Dr. Offit says. “But not for all.” In a perspective published Jan. 11 in the New England Journal of Medicine – the same issue that published the two studies finding few differences between the original and bivalent – Dr. Offit wrote that boosting is best reserved for vulnerable groups.

Chasing the variants with a bivalent vaccine, he says, “has not panned out. There remains no evidence that a bivalent vaccine is any better than what we had. Please, show me the data that one is better than the other.”

Dr. Offit believes the goal should not be to prevent all symptomatic infections in healthy, young people by boosting them “with vaccines containing mRNA from strains that might disappear a few months later.”

The CDC needs to parse the data by subgroups, Dr. Offit says. “The critical question is, ‘Who gets hospitalized and who is dying? Who are they?’ ”

That data should take into account age, ethnicity, vaccine history, and other factors, Dr. Offit says, because right now, there is no great data to say, “OK, everyone gets a boost.”
 

Future vaccine costs

Another debate – for not only current boosters but future ones, too – centers on cost. Without congressional action to fund more vaccines, vaccine makers have suggested their prices may reach $130 a dose, compared with the average $20-per-dose cost the federal government pays now, according to a Kaiser Family Foundation report.

The government has spent more than $30 billion on COVID-19 vaccines, including the bivalent, to provide them free of charge.

The suggested price increase infuriated many. On Jan. 10, Sen. Bernie Sanders (I-Vt.), incoming chair of the Senate Committee on Health, Education, Labor and Pensions, sent a letter to Moderna CEO Stéphane Bancel, urging him to reconsider and refrain from any price increase.

“The huge increase in price that you have proposed will have a significantly negative impact on the budgets of Medicaid, Medicare and other government programs that will continue covering the vaccine without cost-sharing for patients.”

He pointed out, too, the $19 billion in profits Moderna has made over the past 2 years.

While most people with health insurance would likely still get the vaccines and booster for free, according to the Kaiser analysis, will a higher price discourage people from keeping up with recommended vaccinations, including a possible new booster?

“I think so, yes,” Dr. Hotez says, noting that vaccine reluctance is high as it is, even with free vaccinations and easy access.

“The government is balking at paying for the boosters,” he says. “I think it’s very tone deaf from the pharmaceutical companies [to increase the price]. Given all the help they’ve gotten from the American people, I think they should not be gouging at this point.”

He noted that the federal government provided not just money to the companies for the vaccines, but a “glide path” through the FDA for the vaccine approvals.
 

Are new, variant-specific boosters coming?

Are Moderna, Pfizer-BioNTech, and others developing more variant-specific vaccines, boosters, or other advances?

Novavax, approved in July 2022 as a primary series and in some cases as a booster, is “also developing an Omicron-containing bivalent vaccine at the direction of public health agencies,” says spokesperson Alison Chartan.

Pfizer responded: “When and if we have something to share we will let you know.”

Moderna did not respond.

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

On Twitter, as in real life, it’s a question on many minds: When should we think about the next COVID-19 vaccine? Or should we?

For some people who have received a two-dose primary series and all the recommended boosters, that could mean a sixth shot since COVID-19 vaccines became available. But is even that enough (or too much)?

At this point, no one knows for sure, but new guidance may be on the docket.

On Jan. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee is meeting. On the agenda is discussion about plans for future vaccinations for COVID-19.The committee, made up of external advisers, evaluates data on vaccines and other products for the agency.

According to the FDA announcement, after the meeting, “the FDA will consider whether to recommend adjustments to the current authorizations and approvals, and the FDA will consider the most efficient and transparent process to use for selection of strains for inclusion in the primary and booster vaccines.”

From there, the CDC will take up the issue and decide on recommendations.

The issue is important, as more than 550 Americans a day are still dying from COVID-19, as of the week ending Jan. 13, the CDC reported. That’s up from 346 a day for the week ending Dec. 28.

Yet, uptake of the newest vaccine, the bivalent booster, has been slow. As of Jan. 11, just 15.9% of the population 5 years and up has gotten it; for those most vulnerable to COVID19 – those 65 and up – the number is just 39%.
 

COVID vaccines, 2023 and beyond

Meanwhile, infectious disease experts have widely differing views on what the vaccination landscape of 2023 and beyond should look like. Among the areas of disagreement are how effective the bivalent vaccine is, which people most need another shot, and what type of vaccine is best.

“I think we probably will need another booster,” says Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, and codirector of the Center for Vaccine Development at Texas Children’s Hospital in Houston. “The question is, what is it going to be? Is it going to be the same bivalent that we just got, or will it be a new bivalent or even a trivalent?” 

The trivalent booster, he suggested, might include something more protective against XBB.1.5.

The bivalent booster gives “broadened immunity” that is improved from the original booster shots, says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape, WebMD’s sister site for health professionals.

In his publication Ground Truths, Dr. Topol on Jan. 11 explained how new data caused him to reverse his previously skeptical view of how the FDA authorized the bivalent vaccine in September without data on how it affected humans at the time.

Paul Offit, MD, director of the Vaccine Education Center and a professor of pediatrics at the Children’s Hospital of Philadelphia, is a member of the FDA advisory committee for vaccines. He still takes a dimmer view of more bivalent booster vaccines, at least as a blanket recommendation. 

While he acknowledges that boosters can help some groups – such as older adults, people with multiple health conditions, and those with compromised immune systems – he opposes a recommendation that’s population-wide.

“People who fall into those three groups do benefit,” he says, “but the recommendation is everyone over 6 months get the bivalent, and what I’m asking is, ‘Where is the data that a healthy 12-year-old boy needs a booster to stay out of the hospital?’ ”
 

Evolving research

“We are trying to understand how to stay one step ahead rather than several steps behind [the virus],“ says Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Among the key questions: How well can a vaccine work against a single subvariant, when no one can say for sure what the next predominant subvariant will be?

Much more research has become available recently about the bivalent vaccine and its effectiveness, Dr. Osterholm says. “The bivalent vaccine is working as well as we could have expected,” he says, especially in high-risk people and in those over age 65. “The challenge we have is, what does that mean going forward?”

In his review, Dr. Topol concludes: “There is now more than ample, highly consistent evidence via lab studies and clinical outcomes to support the bivalent’s benefit over the original booster.”

Among other evidence, he looked at eight studies, including four that used a live virus as part of the research. Six of the eight studies showed the bivalent booster is more effective against the BA.5 variant, compared with the original booster shots. Two others showed no real difference.

“The four live virus studies offer consistent evidence of broadened immunity for the BA.5 vaccine that is improved over the original booster shots,” Dr. Topol wrote. The evidence also found the bivalent antibody response superior against XBB, he wrote.

Dr. Topol also cited CDC data that supports the benefits of the bivalent shot on hospitalization in older adults. During November, hospitalization of adults 65 and above was 2.5 times higher for those vaccinated who did not get the booster, compared to those who got the updated bivalent booster.

Boosters do matter, Dr. Offit says. “But not for all.” In a perspective published Jan. 11 in the New England Journal of Medicine – the same issue that published the two studies finding few differences between the original and bivalent – Dr. Offit wrote that boosting is best reserved for vulnerable groups.

Chasing the variants with a bivalent vaccine, he says, “has not panned out. There remains no evidence that a bivalent vaccine is any better than what we had. Please, show me the data that one is better than the other.”

Dr. Offit believes the goal should not be to prevent all symptomatic infections in healthy, young people by boosting them “with vaccines containing mRNA from strains that might disappear a few months later.”

The CDC needs to parse the data by subgroups, Dr. Offit says. “The critical question is, ‘Who gets hospitalized and who is dying? Who are they?’ ”

That data should take into account age, ethnicity, vaccine history, and other factors, Dr. Offit says, because right now, there is no great data to say, “OK, everyone gets a boost.”
 

Future vaccine costs

Another debate – for not only current boosters but future ones, too – centers on cost. Without congressional action to fund more vaccines, vaccine makers have suggested their prices may reach $130 a dose, compared with the average $20-per-dose cost the federal government pays now, according to a Kaiser Family Foundation report.

The government has spent more than $30 billion on COVID-19 vaccines, including the bivalent, to provide them free of charge.

The suggested price increase infuriated many. On Jan. 10, Sen. Bernie Sanders (I-Vt.), incoming chair of the Senate Committee on Health, Education, Labor and Pensions, sent a letter to Moderna CEO Stéphane Bancel, urging him to reconsider and refrain from any price increase.

“The huge increase in price that you have proposed will have a significantly negative impact on the budgets of Medicaid, Medicare and other government programs that will continue covering the vaccine without cost-sharing for patients.”

He pointed out, too, the $19 billion in profits Moderna has made over the past 2 years.

While most people with health insurance would likely still get the vaccines and booster for free, according to the Kaiser analysis, will a higher price discourage people from keeping up with recommended vaccinations, including a possible new booster?

“I think so, yes,” Dr. Hotez says, noting that vaccine reluctance is high as it is, even with free vaccinations and easy access.

“The government is balking at paying for the boosters,” he says. “I think it’s very tone deaf from the pharmaceutical companies [to increase the price]. Given all the help they’ve gotten from the American people, I think they should not be gouging at this point.”

He noted that the federal government provided not just money to the companies for the vaccines, but a “glide path” through the FDA for the vaccine approvals.
 

Are new, variant-specific boosters coming?

Are Moderna, Pfizer-BioNTech, and others developing more variant-specific vaccines, boosters, or other advances?

Novavax, approved in July 2022 as a primary series and in some cases as a booster, is “also developing an Omicron-containing bivalent vaccine at the direction of public health agencies,” says spokesperson Alison Chartan.

Pfizer responded: “When and if we have something to share we will let you know.”

Moderna did not respond.

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

On Twitter, as in real life, it’s a question on many minds: When should we think about the next COVID-19 vaccine? Or should we?

For some people who have received a two-dose primary series and all the recommended boosters, that could mean a sixth shot since COVID-19 vaccines became available. But is even that enough (or too much)?

At this point, no one knows for sure, but new guidance may be on the docket.

On Jan. 26, the FDA’s Vaccines and Related Biological Products Advisory Committee is meeting. On the agenda is discussion about plans for future vaccinations for COVID-19.The committee, made up of external advisers, evaluates data on vaccines and other products for the agency.

According to the FDA announcement, after the meeting, “the FDA will consider whether to recommend adjustments to the current authorizations and approvals, and the FDA will consider the most efficient and transparent process to use for selection of strains for inclusion in the primary and booster vaccines.”

From there, the CDC will take up the issue and decide on recommendations.

The issue is important, as more than 550 Americans a day are still dying from COVID-19, as of the week ending Jan. 13, the CDC reported. That’s up from 346 a day for the week ending Dec. 28.

Yet, uptake of the newest vaccine, the bivalent booster, has been slow. As of Jan. 11, just 15.9% of the population 5 years and up has gotten it; for those most vulnerable to COVID19 – those 65 and up – the number is just 39%.
 

COVID vaccines, 2023 and beyond

Meanwhile, infectious disease experts have widely differing views on what the vaccination landscape of 2023 and beyond should look like. Among the areas of disagreement are how effective the bivalent vaccine is, which people most need another shot, and what type of vaccine is best.

“I think we probably will need another booster,” says Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, and codirector of the Center for Vaccine Development at Texas Children’s Hospital in Houston. “The question is, what is it going to be? Is it going to be the same bivalent that we just got, or will it be a new bivalent or even a trivalent?” 

The trivalent booster, he suggested, might include something more protective against XBB.1.5.

The bivalent booster gives “broadened immunity” that is improved from the original booster shots, says Eric Topol, MD, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and editor-in-chief of Medscape, WebMD’s sister site for health professionals.

In his publication Ground Truths, Dr. Topol on Jan. 11 explained how new data caused him to reverse his previously skeptical view of how the FDA authorized the bivalent vaccine in September without data on how it affected humans at the time.

Paul Offit, MD, director of the Vaccine Education Center and a professor of pediatrics at the Children’s Hospital of Philadelphia, is a member of the FDA advisory committee for vaccines. He still takes a dimmer view of more bivalent booster vaccines, at least as a blanket recommendation. 

While he acknowledges that boosters can help some groups – such as older adults, people with multiple health conditions, and those with compromised immune systems – he opposes a recommendation that’s population-wide.

“People who fall into those three groups do benefit,” he says, “but the recommendation is everyone over 6 months get the bivalent, and what I’m asking is, ‘Where is the data that a healthy 12-year-old boy needs a booster to stay out of the hospital?’ ”
 

Evolving research

“We are trying to understand how to stay one step ahead rather than several steps behind [the virus],“ says Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Among the key questions: How well can a vaccine work against a single subvariant, when no one can say for sure what the next predominant subvariant will be?

Much more research has become available recently about the bivalent vaccine and its effectiveness, Dr. Osterholm says. “The bivalent vaccine is working as well as we could have expected,” he says, especially in high-risk people and in those over age 65. “The challenge we have is, what does that mean going forward?”

In his review, Dr. Topol concludes: “There is now more than ample, highly consistent evidence via lab studies and clinical outcomes to support the bivalent’s benefit over the original booster.”

Among other evidence, he looked at eight studies, including four that used a live virus as part of the research. Six of the eight studies showed the bivalent booster is more effective against the BA.5 variant, compared with the original booster shots. Two others showed no real difference.

“The four live virus studies offer consistent evidence of broadened immunity for the BA.5 vaccine that is improved over the original booster shots,” Dr. Topol wrote. The evidence also found the bivalent antibody response superior against XBB, he wrote.

Dr. Topol also cited CDC data that supports the benefits of the bivalent shot on hospitalization in older adults. During November, hospitalization of adults 65 and above was 2.5 times higher for those vaccinated who did not get the booster, compared to those who got the updated bivalent booster.

Boosters do matter, Dr. Offit says. “But not for all.” In a perspective published Jan. 11 in the New England Journal of Medicine – the same issue that published the two studies finding few differences between the original and bivalent – Dr. Offit wrote that boosting is best reserved for vulnerable groups.

Chasing the variants with a bivalent vaccine, he says, “has not panned out. There remains no evidence that a bivalent vaccine is any better than what we had. Please, show me the data that one is better than the other.”

Dr. Offit believes the goal should not be to prevent all symptomatic infections in healthy, young people by boosting them “with vaccines containing mRNA from strains that might disappear a few months later.”

The CDC needs to parse the data by subgroups, Dr. Offit says. “The critical question is, ‘Who gets hospitalized and who is dying? Who are they?’ ”

That data should take into account age, ethnicity, vaccine history, and other factors, Dr. Offit says, because right now, there is no great data to say, “OK, everyone gets a boost.”
 

Future vaccine costs

Another debate – for not only current boosters but future ones, too – centers on cost. Without congressional action to fund more vaccines, vaccine makers have suggested their prices may reach $130 a dose, compared with the average $20-per-dose cost the federal government pays now, according to a Kaiser Family Foundation report.

The government has spent more than $30 billion on COVID-19 vaccines, including the bivalent, to provide them free of charge.

The suggested price increase infuriated many. On Jan. 10, Sen. Bernie Sanders (I-Vt.), incoming chair of the Senate Committee on Health, Education, Labor and Pensions, sent a letter to Moderna CEO Stéphane Bancel, urging him to reconsider and refrain from any price increase.

“The huge increase in price that you have proposed will have a significantly negative impact on the budgets of Medicaid, Medicare and other government programs that will continue covering the vaccine without cost-sharing for patients.”

He pointed out, too, the $19 billion in profits Moderna has made over the past 2 years.

While most people with health insurance would likely still get the vaccines and booster for free, according to the Kaiser analysis, will a higher price discourage people from keeping up with recommended vaccinations, including a possible new booster?

“I think so, yes,” Dr. Hotez says, noting that vaccine reluctance is high as it is, even with free vaccinations and easy access.

“The government is balking at paying for the boosters,” he says. “I think it’s very tone deaf from the pharmaceutical companies [to increase the price]. Given all the help they’ve gotten from the American people, I think they should not be gouging at this point.”

He noted that the federal government provided not just money to the companies for the vaccines, but a “glide path” through the FDA for the vaccine approvals.
 

Are new, variant-specific boosters coming?

Are Moderna, Pfizer-BioNTech, and others developing more variant-specific vaccines, boosters, or other advances?

Novavax, approved in July 2022 as a primary series and in some cases as a booster, is “also developing an Omicron-containing bivalent vaccine at the direction of public health agencies,” says spokesperson Alison Chartan.

Pfizer responded: “When and if we have something to share we will let you know.”

Moderna did not respond.

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

Consuming a large amount of nitrites from food additives versus none was associated with a greater risk of developing type 2 diabetes in the NutriNet-Santé study in France, researchers report.

JackF/iStock/Getty Images

However, a few experts who were not involved with this research question the strength of the findings because of study limitations.

The study involved more than 100,000 adults with a mean age of 43, and 79% were women.

Individuals with the highest intakes of nitrites from food additives (top third) had a 53% higher risk of developing type 2 diabetes during a median follow-up of 7 years compared with those with the lowest intake of this food additive after controlling for intake of sugars, red and processed meats, heme iron, salt, and saturated fatty acids. Consumption of nitrates from food additives was not associated with risk of type 2 diabetes.

“Our findings suggest a direct association between additives-originated nitrites and [type 2 diabetes] risk and corroborate previously suggested associations between total dietary nitrites and [type 2 diabetes],” the researchers report in an article published online in PLoS Medicine.

However, “as this is the first large-scale study finding these associations, these results need to be replicated in other large-scale cohorts,” senior author Mathilde Touvier, PhD, head of the Nutritional Epidemiology Research Team (EREN-CRESS), INSERM, INRAE, Sorbonne Paris Nord University, and lead author Bernard Srour, PhD, PharmD, a scientist at the same institution, said in a joint email to this news organization.

Short-term intervention studies to determine insulin resistance could also be tested, they add.

In the meantime, “this study adds further evidence to the existing strong link between nitrites and colorectal cancer risk, and supports the importance of further regulation of nitrites as food additives and nitrogen fertilizers,” they say.

According to Dr. Touvier and Dr. Srour, the takeaway message for clinicians is the finding that nitrites from food additives are associated with type 2 diabetes, “support existing guidelines recommending [limiting] the consumption of processed meats to prevent chronic diseases. However, the consumption of vegetables should be encouraged as they contain several beneficial compounds and contribute to chronic disease prevention.”
 

Some experts are skeptical

But three experts who were not involved with the research were skeptical about the conclusions, in comments made to the U.K. Science Media Centre.

“The fundamental weakness of this study is how the food additive intake was assessed,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London. “Estimates of intake were based on recalls of dietary intake on two separate occasions at the beginning of the study with no further estimates in the follow-up period of over 7 years,” he noted.

Other limitations include the relatively young age of the cohort and relatively low incidence of new cases of type 2 diabetes (about 1% of the study population over 7 years).

Moreover, the level of nitrite food additive ingestion is much lower than the acceptable daily intake. The findings would need to be replicated with appropriate adjustment for differences in body weight.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, said that “the study does not support the claim in the press release and paper that food additives are responsible for the increased risk.”

He pointed out that “nitrite from additives contributes only about 4%-6% of total nitrite intake in the population, and it is not clear why this should have a stronger impact on risk than nitrite from other sources,” such as nitrate found in food and water.

Duane Mellor, PhD, registered dietitian and senior lecturer, Aston University, Birmingham, England, said: “It could be questioned how accurate estimating intakes of individual additives like sodium nitrite, which was less than 1 mg per day from a record of just 2 days food intake per year, as it assumes people ate the same the other 363 days of the year.”

Moreover, “it is perhaps worth noting that the use of nitrites as an additive is often as sodium nitrite, which is used to cure meats like bacon, which if someone is seeking to reduce their risk of type 2 diabetes would be something people would be encouraged to eat less of [anyway].”

“The best way to reduce your risk of developing type 2 diabetes,” he said, “is to be physically active, maintain a healthy weight for you, and eat a varied diet based on vegetables, pulses, nuts, seeds, and fruit along with wholegrain and moderate intakes of dairy foods and meat (especially processed meats).”
 

Study details

Nitrites and nitrates are used as food additives to prevent bacterial growth, mainly in processed meats, and they are also found in foods (mainly green leafy vegetables) and water (nitrates from the use of nitrogen fertilizer can enter the water supply).

The researchers analyzed data from 104,168 participants in NutriNet-Santé who had no diabetes at baseline and who completed 24-hour dietary intake records. They investigated the association between exposure to nitrites and nitrates (in food and water or in additives) and incident type 2 diabetes.

Most nitrites came from food (95.3%), and less often from food additives (4.7%) and water (< 0.01%). The nitrites in foods were mainly from vegetables (60%) and seasonings (23%).

Most nitrates also came from food (93%), followed by water (6.9%) and food additives (0.1%). The nitrates in foods were mainly from vegetables (41%), processed meat (19%), and meat (17%).

During a median follow-up of 7.3 years, there were 969 incident cases of type 2 diabetes.

Compared with individuals in the lowest third of nitrites from food and water, those in the highest tertile had a 27% higher risk of incident type 2 diabetes, after adjusting for multiple variables (hazard ratio, 1.27; P = .009).

The risk of type 2 diabetes associated with the highest intake of nitrites from additives was as previously described, 53% higher, than that for those with the lowest intake.

There was no evidence of an association between nitrates and risk of type 2 diabetes.

The researchers acknowledge that study limitations include potential errors in assessment of nitrate and nitrate exposure, potential selection bias (participants in the web-based study may have had healthier behaviors than the general population), and potential unaccounted confounders (because it was an observational study).

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

Consuming a large amount of nitrites from food additives versus none was associated with a greater risk of developing type 2 diabetes in the NutriNet-Santé study in France, researchers report.

JackF/iStock/Getty Images

However, a few experts who were not involved with this research question the strength of the findings because of study limitations.

The study involved more than 100,000 adults with a mean age of 43, and 79% were women.

Individuals with the highest intakes of nitrites from food additives (top third) had a 53% higher risk of developing type 2 diabetes during a median follow-up of 7 years compared with those with the lowest intake of this food additive after controlling for intake of sugars, red and processed meats, heme iron, salt, and saturated fatty acids. Consumption of nitrates from food additives was not associated with risk of type 2 diabetes.

“Our findings suggest a direct association between additives-originated nitrites and [type 2 diabetes] risk and corroborate previously suggested associations between total dietary nitrites and [type 2 diabetes],” the researchers report in an article published online in PLoS Medicine.

However, “as this is the first large-scale study finding these associations, these results need to be replicated in other large-scale cohorts,” senior author Mathilde Touvier, PhD, head of the Nutritional Epidemiology Research Team (EREN-CRESS), INSERM, INRAE, Sorbonne Paris Nord University, and lead author Bernard Srour, PhD, PharmD, a scientist at the same institution, said in a joint email to this news organization.

Short-term intervention studies to determine insulin resistance could also be tested, they add.

In the meantime, “this study adds further evidence to the existing strong link between nitrites and colorectal cancer risk, and supports the importance of further regulation of nitrites as food additives and nitrogen fertilizers,” they say.

According to Dr. Touvier and Dr. Srour, the takeaway message for clinicians is the finding that nitrites from food additives are associated with type 2 diabetes, “support existing guidelines recommending [limiting] the consumption of processed meats to prevent chronic diseases. However, the consumption of vegetables should be encouraged as they contain several beneficial compounds and contribute to chronic disease prevention.”
 

Some experts are skeptical

But three experts who were not involved with the research were skeptical about the conclusions, in comments made to the U.K. Science Media Centre.

“The fundamental weakness of this study is how the food additive intake was assessed,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London. “Estimates of intake were based on recalls of dietary intake on two separate occasions at the beginning of the study with no further estimates in the follow-up period of over 7 years,” he noted.

Other limitations include the relatively young age of the cohort and relatively low incidence of new cases of type 2 diabetes (about 1% of the study population over 7 years).

Moreover, the level of nitrite food additive ingestion is much lower than the acceptable daily intake. The findings would need to be replicated with appropriate adjustment for differences in body weight.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, said that “the study does not support the claim in the press release and paper that food additives are responsible for the increased risk.”

He pointed out that “nitrite from additives contributes only about 4%-6% of total nitrite intake in the population, and it is not clear why this should have a stronger impact on risk than nitrite from other sources,” such as nitrate found in food and water.

Duane Mellor, PhD, registered dietitian and senior lecturer, Aston University, Birmingham, England, said: “It could be questioned how accurate estimating intakes of individual additives like sodium nitrite, which was less than 1 mg per day from a record of just 2 days food intake per year, as it assumes people ate the same the other 363 days of the year.”

Moreover, “it is perhaps worth noting that the use of nitrites as an additive is often as sodium nitrite, which is used to cure meats like bacon, which if someone is seeking to reduce their risk of type 2 diabetes would be something people would be encouraged to eat less of [anyway].”

“The best way to reduce your risk of developing type 2 diabetes,” he said, “is to be physically active, maintain a healthy weight for you, and eat a varied diet based on vegetables, pulses, nuts, seeds, and fruit along with wholegrain and moderate intakes of dairy foods and meat (especially processed meats).”
 

Study details

Nitrites and nitrates are used as food additives to prevent bacterial growth, mainly in processed meats, and they are also found in foods (mainly green leafy vegetables) and water (nitrates from the use of nitrogen fertilizer can enter the water supply).

The researchers analyzed data from 104,168 participants in NutriNet-Santé who had no diabetes at baseline and who completed 24-hour dietary intake records. They investigated the association between exposure to nitrites and nitrates (in food and water or in additives) and incident type 2 diabetes.

Most nitrites came from food (95.3%), and less often from food additives (4.7%) and water (< 0.01%). The nitrites in foods were mainly from vegetables (60%) and seasonings (23%).

Most nitrates also came from food (93%), followed by water (6.9%) and food additives (0.1%). The nitrates in foods were mainly from vegetables (41%), processed meat (19%), and meat (17%).

During a median follow-up of 7.3 years, there were 969 incident cases of type 2 diabetes.

Compared with individuals in the lowest third of nitrites from food and water, those in the highest tertile had a 27% higher risk of incident type 2 diabetes, after adjusting for multiple variables (hazard ratio, 1.27; P = .009).

The risk of type 2 diabetes associated with the highest intake of nitrites from additives was as previously described, 53% higher, than that for those with the lowest intake.

There was no evidence of an association between nitrates and risk of type 2 diabetes.

The researchers acknowledge that study limitations include potential errors in assessment of nitrate and nitrate exposure, potential selection bias (participants in the web-based study may have had healthier behaviors than the general population), and potential unaccounted confounders (because it was an observational study).

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

Consuming a large amount of nitrites from food additives versus none was associated with a greater risk of developing type 2 diabetes in the NutriNet-Santé study in France, researchers report.

JackF/iStock/Getty Images

However, a few experts who were not involved with this research question the strength of the findings because of study limitations.

The study involved more than 100,000 adults with a mean age of 43, and 79% were women.

Individuals with the highest intakes of nitrites from food additives (top third) had a 53% higher risk of developing type 2 diabetes during a median follow-up of 7 years compared with those with the lowest intake of this food additive after controlling for intake of sugars, red and processed meats, heme iron, salt, and saturated fatty acids. Consumption of nitrates from food additives was not associated with risk of type 2 diabetes.

“Our findings suggest a direct association between additives-originated nitrites and [type 2 diabetes] risk and corroborate previously suggested associations between total dietary nitrites and [type 2 diabetes],” the researchers report in an article published online in PLoS Medicine.

However, “as this is the first large-scale study finding these associations, these results need to be replicated in other large-scale cohorts,” senior author Mathilde Touvier, PhD, head of the Nutritional Epidemiology Research Team (EREN-CRESS), INSERM, INRAE, Sorbonne Paris Nord University, and lead author Bernard Srour, PhD, PharmD, a scientist at the same institution, said in a joint email to this news organization.

Short-term intervention studies to determine insulin resistance could also be tested, they add.

In the meantime, “this study adds further evidence to the existing strong link between nitrites and colorectal cancer risk, and supports the importance of further regulation of nitrites as food additives and nitrogen fertilizers,” they say.

According to Dr. Touvier and Dr. Srour, the takeaway message for clinicians is the finding that nitrites from food additives are associated with type 2 diabetes, “support existing guidelines recommending [limiting] the consumption of processed meats to prevent chronic diseases. However, the consumption of vegetables should be encouraged as they contain several beneficial compounds and contribute to chronic disease prevention.”
 

Some experts are skeptical

But three experts who were not involved with the research were skeptical about the conclusions, in comments made to the U.K. Science Media Centre.

“The fundamental weakness of this study is how the food additive intake was assessed,” said Tom Sanders, DSc, PhD, professor emeritus of nutrition and dietetics, King’s College London. “Estimates of intake were based on recalls of dietary intake on two separate occasions at the beginning of the study with no further estimates in the follow-up period of over 7 years,” he noted.

Other limitations include the relatively young age of the cohort and relatively low incidence of new cases of type 2 diabetes (about 1% of the study population over 7 years).

Moreover, the level of nitrite food additive ingestion is much lower than the acceptable daily intake. The findings would need to be replicated with appropriate adjustment for differences in body weight.

Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading, England, said that “the study does not support the claim in the press release and paper that food additives are responsible for the increased risk.”

He pointed out that “nitrite from additives contributes only about 4%-6% of total nitrite intake in the population, and it is not clear why this should have a stronger impact on risk than nitrite from other sources,” such as nitrate found in food and water.

Duane Mellor, PhD, registered dietitian and senior lecturer, Aston University, Birmingham, England, said: “It could be questioned how accurate estimating intakes of individual additives like sodium nitrite, which was less than 1 mg per day from a record of just 2 days food intake per year, as it assumes people ate the same the other 363 days of the year.”

Moreover, “it is perhaps worth noting that the use of nitrites as an additive is often as sodium nitrite, which is used to cure meats like bacon, which if someone is seeking to reduce their risk of type 2 diabetes would be something people would be encouraged to eat less of [anyway].”

“The best way to reduce your risk of developing type 2 diabetes,” he said, “is to be physically active, maintain a healthy weight for you, and eat a varied diet based on vegetables, pulses, nuts, seeds, and fruit along with wholegrain and moderate intakes of dairy foods and meat (especially processed meats).”
 

Study details

Nitrites and nitrates are used as food additives to prevent bacterial growth, mainly in processed meats, and they are also found in foods (mainly green leafy vegetables) and water (nitrates from the use of nitrogen fertilizer can enter the water supply).

The researchers analyzed data from 104,168 participants in NutriNet-Santé who had no diabetes at baseline and who completed 24-hour dietary intake records. They investigated the association between exposure to nitrites and nitrates (in food and water or in additives) and incident type 2 diabetes.

Most nitrites came from food (95.3%), and less often from food additives (4.7%) and water (< 0.01%). The nitrites in foods were mainly from vegetables (60%) and seasonings (23%).

Most nitrates also came from food (93%), followed by water (6.9%) and food additives (0.1%). The nitrates in foods were mainly from vegetables (41%), processed meat (19%), and meat (17%).

During a median follow-up of 7.3 years, there were 969 incident cases of type 2 diabetes.

Compared with individuals in the lowest third of nitrites from food and water, those in the highest tertile had a 27% higher risk of incident type 2 diabetes, after adjusting for multiple variables (hazard ratio, 1.27; P = .009).

The risk of type 2 diabetes associated with the highest intake of nitrites from additives was as previously described, 53% higher, than that for those with the lowest intake.

There was no evidence of an association between nitrates and risk of type 2 diabetes.

The researchers acknowledge that study limitations include potential errors in assessment of nitrate and nitrate exposure, potential selection bias (participants in the web-based study may have had healthier behaviors than the general population), and potential unaccounted confounders (because it was an observational study).

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

In a new retrospective analysis of patients with above-average risk of colorectal cancer, multiple negative fecal immunohistochemical tests (FITs) were associated with a lower risk of advanced neoplasia. The findings suggest that multiple negative FITs could potentially identify individuals in high-risk surveillance who aren’t truly high risk, which could in turn ease the logjam of colonoscopies and free resources for truly high-risk individuals.

The study, conducted in Australia, was published online in Clinical Gastroenterology and Hepatology. It included patients who completed at least two FIT exams between surveillance colonoscopies and had no neoplasia or nonadvanced adenoma at prior colonoscopy. Above-average risk was defined as a family history or by findings at surveillance colonoscopy.

The study has some limitations. It is a retrospective analysis between the years 2008 and 2019, and colonoscopy guidelines in the United States have since changed, with a recommendation of surveillance colonoscopy at 7-10 years following 1-2 adenomas discovered at surveillance colonoscopy, and the current study includes follow-up colonoscopy at 5 years. “These data are informative for patients up to 5 years, but they’re not really informative afterwards. They just don’t have those data yet,” said Reed Ness, MD, who was asked to comment on the study.

The authors also don’t describe what they mean by a family history of colorectal cancer risk. “My take was that it’s an interesting result which would seem to support the possibility of returning some patients with a family history or adenoma history to a noncolonoscopy screening regimen after a negative surveillance colonoscopy. We’ll need to see where the data lead us in the future,” said Dr. Ness, who is an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“We’re letting people go 10 years now, and some people are uncomfortable with allowing patients to go 10 years. So you could think of a scenario where you use FIT to try to find people that might have higher-risk lesions that need to come back for colonoscopy within that 10 years,” said Dr. Ness. That issue is particularly relevant given the wide range of adenoma detection rates among gastroenterologists, because FIT could detect a polyp that was missed during a colonoscopy.

The study included two groups with increased risk – those with a family history of colon cancer, and those with previously detected adenomas. The family history cohort may be useful for clinical practice, according to Priyanka Kanth, MD, who was also asked to comment on the study. “Some people may not need [a colonoscopy] at 5 years if they have no polyps found and negative FIT,” said Dr. Kanth, who is an associate professor of gastroenterology at Georgetown University, Washington.

She feels less certain about the group with previously detected adenomas, given the change in U.S. guidelines. “We have already changed that, so I don’t think we need to really do FIT intervals for that cohort,” said Dr. Kanth. “I think this is a good study that has a lot of information and also reassures us that we don’t need such frequent colonoscopy surveillance,” she added.

Steve Serrao, MD, PhD, who was also asked for comment, emphasized the importance of high-quality colonoscopies that reach the cecum 95% of the time, and achieving high adenoma-detection rates. The system can get overwhelmed conducting colonoscopies on patients with good insurance coverage who have already undergone high-quality colonoscopies. “That pushes out patients that haven’t necessarily had a colonoscopy or a FIT. People who don’t have access are kind of crowded out by these false-positive tests. The best modality is actually to do a high-quality colonoscopy and then to have a really well-directed strategy following that colonoscopy,” said Dr. Serrao, who is division chief of gastroenterology and hepatology at Riverside University Health System, Moreno Valley, Calif.

The researchers analyzed data from 4,021 surveillance intervals and 3,369 participants. A total of 1,436 had no neoplasia at the prior colonoscopy, 1,704 had nonadvanced adenoma, and 880 had advanced adenoma. Participants completed no or one to four FIT tests between colonoscopies, with the final colonoscopy performed within 2 years of FIT tests. The median age was 63.9 years; 53.6% were female; 71.1% had a prior adenoma; and 28.9% had a family history of colorectal cancer. A total of 29.4% of participants had one negative FIT; 6.9% had four negative FITs during the interval period; and 31.0% did not complete any FIT tests.

Of follow-up colonoscopies, 9.9% revealed advanced adenomas. Among the patients with no prior neoplasia, those with one negative FIT had a cumulative index function for advanced neoplasia at 5 years of 8.5% (95% confidence interval, 4.9%-13.3%). This was higher than for those with three negative FITs (4.5%; 95% CI, 2.0%-8.6%) or four negative FITs (1.9%; 95% CI, 0.5%-5.0%). The association held for individuals with prior nonadvanced adenoma but not those with advanced adenoma.

Over the 5-year interval, three or more negative FIT tests were associated with a 50%-70% reduction in advanced neoplasia risk at follow-up colonoscopy (P < .001). There was no significant association over a 3-year interval. Dr. Kanth, Dr. Serrao, and Dr. Ness have no relevant financial disclosures.
 

In a new retrospective analysis of patients with above-average risk of colorectal cancer, multiple negative fecal immunohistochemical tests (FITs) were associated with a lower risk of advanced neoplasia. The findings suggest that multiple negative FITs could potentially identify individuals in high-risk surveillance who aren’t truly high risk, which could in turn ease the logjam of colonoscopies and free resources for truly high-risk individuals.

The study, conducted in Australia, was published online in Clinical Gastroenterology and Hepatology. It included patients who completed at least two FIT exams between surveillance colonoscopies and had no neoplasia or nonadvanced adenoma at prior colonoscopy. Above-average risk was defined as a family history or by findings at surveillance colonoscopy.

The study has some limitations. It is a retrospective analysis between the years 2008 and 2019, and colonoscopy guidelines in the United States have since changed, with a recommendation of surveillance colonoscopy at 7-10 years following 1-2 adenomas discovered at surveillance colonoscopy, and the current study includes follow-up colonoscopy at 5 years. “These data are informative for patients up to 5 years, but they’re not really informative afterwards. They just don’t have those data yet,” said Reed Ness, MD, who was asked to comment on the study.

The authors also don’t describe what they mean by a family history of colorectal cancer risk. “My take was that it’s an interesting result which would seem to support the possibility of returning some patients with a family history or adenoma history to a noncolonoscopy screening regimen after a negative surveillance colonoscopy. We’ll need to see where the data lead us in the future,” said Dr. Ness, who is an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“We’re letting people go 10 years now, and some people are uncomfortable with allowing patients to go 10 years. So you could think of a scenario where you use FIT to try to find people that might have higher-risk lesions that need to come back for colonoscopy within that 10 years,” said Dr. Ness. That issue is particularly relevant given the wide range of adenoma detection rates among gastroenterologists, because FIT could detect a polyp that was missed during a colonoscopy.

The study included two groups with increased risk – those with a family history of colon cancer, and those with previously detected adenomas. The family history cohort may be useful for clinical practice, according to Priyanka Kanth, MD, who was also asked to comment on the study. “Some people may not need [a colonoscopy] at 5 years if they have no polyps found and negative FIT,” said Dr. Kanth, who is an associate professor of gastroenterology at Georgetown University, Washington.

She feels less certain about the group with previously detected adenomas, given the change in U.S. guidelines. “We have already changed that, so I don’t think we need to really do FIT intervals for that cohort,” said Dr. Kanth. “I think this is a good study that has a lot of information and also reassures us that we don’t need such frequent colonoscopy surveillance,” she added.

Steve Serrao, MD, PhD, who was also asked for comment, emphasized the importance of high-quality colonoscopies that reach the cecum 95% of the time, and achieving high adenoma-detection rates. The system can get overwhelmed conducting colonoscopies on patients with good insurance coverage who have already undergone high-quality colonoscopies. “That pushes out patients that haven’t necessarily had a colonoscopy or a FIT. People who don’t have access are kind of crowded out by these false-positive tests. The best modality is actually to do a high-quality colonoscopy and then to have a really well-directed strategy following that colonoscopy,” said Dr. Serrao, who is division chief of gastroenterology and hepatology at Riverside University Health System, Moreno Valley, Calif.

The researchers analyzed data from 4,021 surveillance intervals and 3,369 participants. A total of 1,436 had no neoplasia at the prior colonoscopy, 1,704 had nonadvanced adenoma, and 880 had advanced adenoma. Participants completed no or one to four FIT tests between colonoscopies, with the final colonoscopy performed within 2 years of FIT tests. The median age was 63.9 years; 53.6% were female; 71.1% had a prior adenoma; and 28.9% had a family history of colorectal cancer. A total of 29.4% of participants had one negative FIT; 6.9% had four negative FITs during the interval period; and 31.0% did not complete any FIT tests.

Of follow-up colonoscopies, 9.9% revealed advanced adenomas. Among the patients with no prior neoplasia, those with one negative FIT had a cumulative index function for advanced neoplasia at 5 years of 8.5% (95% confidence interval, 4.9%-13.3%). This was higher than for those with three negative FITs (4.5%; 95% CI, 2.0%-8.6%) or four negative FITs (1.9%; 95% CI, 0.5%-5.0%). The association held for individuals with prior nonadvanced adenoma but not those with advanced adenoma.

Over the 5-year interval, three or more negative FIT tests were associated with a 50%-70% reduction in advanced neoplasia risk at follow-up colonoscopy (P < .001). There was no significant association over a 3-year interval. Dr. Kanth, Dr. Serrao, and Dr. Ness have no relevant financial disclosures.
 

In a new retrospective analysis of patients with above-average risk of colorectal cancer, multiple negative fecal immunohistochemical tests (FITs) were associated with a lower risk of advanced neoplasia. The findings suggest that multiple negative FITs could potentially identify individuals in high-risk surveillance who aren’t truly high risk, which could in turn ease the logjam of colonoscopies and free resources for truly high-risk individuals.

The study, conducted in Australia, was published online in Clinical Gastroenterology and Hepatology. It included patients who completed at least two FIT exams between surveillance colonoscopies and had no neoplasia or nonadvanced adenoma at prior colonoscopy. Above-average risk was defined as a family history or by findings at surveillance colonoscopy.

The study has some limitations. It is a retrospective analysis between the years 2008 and 2019, and colonoscopy guidelines in the United States have since changed, with a recommendation of surveillance colonoscopy at 7-10 years following 1-2 adenomas discovered at surveillance colonoscopy, and the current study includes follow-up colonoscopy at 5 years. “These data are informative for patients up to 5 years, but they’re not really informative afterwards. They just don’t have those data yet,” said Reed Ness, MD, who was asked to comment on the study.

The authors also don’t describe what they mean by a family history of colorectal cancer risk. “My take was that it’s an interesting result which would seem to support the possibility of returning some patients with a family history or adenoma history to a noncolonoscopy screening regimen after a negative surveillance colonoscopy. We’ll need to see where the data lead us in the future,” said Dr. Ness, who is an associate professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn.

“We’re letting people go 10 years now, and some people are uncomfortable with allowing patients to go 10 years. So you could think of a scenario where you use FIT to try to find people that might have higher-risk lesions that need to come back for colonoscopy within that 10 years,” said Dr. Ness. That issue is particularly relevant given the wide range of adenoma detection rates among gastroenterologists, because FIT could detect a polyp that was missed during a colonoscopy.

The study included two groups with increased risk – those with a family history of colon cancer, and those with previously detected adenomas. The family history cohort may be useful for clinical practice, according to Priyanka Kanth, MD, who was also asked to comment on the study. “Some people may not need [a colonoscopy] at 5 years if they have no polyps found and negative FIT,” said Dr. Kanth, who is an associate professor of gastroenterology at Georgetown University, Washington.

She feels less certain about the group with previously detected adenomas, given the change in U.S. guidelines. “We have already changed that, so I don’t think we need to really do FIT intervals for that cohort,” said Dr. Kanth. “I think this is a good study that has a lot of information and also reassures us that we don’t need such frequent colonoscopy surveillance,” she added.

Steve Serrao, MD, PhD, who was also asked for comment, emphasized the importance of high-quality colonoscopies that reach the cecum 95% of the time, and achieving high adenoma-detection rates. The system can get overwhelmed conducting colonoscopies on patients with good insurance coverage who have already undergone high-quality colonoscopies. “That pushes out patients that haven’t necessarily had a colonoscopy or a FIT. People who don’t have access are kind of crowded out by these false-positive tests. The best modality is actually to do a high-quality colonoscopy and then to have a really well-directed strategy following that colonoscopy,” said Dr. Serrao, who is division chief of gastroenterology and hepatology at Riverside University Health System, Moreno Valley, Calif.

The researchers analyzed data from 4,021 surveillance intervals and 3,369 participants. A total of 1,436 had no neoplasia at the prior colonoscopy, 1,704 had nonadvanced adenoma, and 880 had advanced adenoma. Participants completed no or one to four FIT tests between colonoscopies, with the final colonoscopy performed within 2 years of FIT tests. The median age was 63.9 years; 53.6% were female; 71.1% had a prior adenoma; and 28.9% had a family history of colorectal cancer. A total of 29.4% of participants had one negative FIT; 6.9% had four negative FITs during the interval period; and 31.0% did not complete any FIT tests.

Of follow-up colonoscopies, 9.9% revealed advanced adenomas. Among the patients with no prior neoplasia, those with one negative FIT had a cumulative index function for advanced neoplasia at 5 years of 8.5% (95% confidence interval, 4.9%-13.3%). This was higher than for those with three negative FITs (4.5%; 95% CI, 2.0%-8.6%) or four negative FITs (1.9%; 95% CI, 0.5%-5.0%). The association held for individuals with prior nonadvanced adenoma but not those with advanced adenoma.

Over the 5-year interval, three or more negative FIT tests were associated with a 50%-70% reduction in advanced neoplasia risk at follow-up colonoscopy (P < .001). There was no significant association over a 3-year interval. Dr. Kanth, Dr. Serrao, and Dr. Ness have no relevant financial disclosures.
 

Patients who received an injection of inclisiran (Leqvio), a small interfering RNA (siRNA) agent, every 6 months for as long as 4 years safely maintained about a 45% reduction from baseline in their level of low-density lipoprotein cholesterol (LDL-C) in an open-label extension study with 382 patients.

In addition to providing the longest reported treatment experience with inclisiran, which received Food and Drug Administration marketing approval a little over a year ago, the results also suggest with the most definitive evidence to date that inclisiran is less effective for lowering LDL-C, compared with a class of medications that reduce LDL-C by a related but distinct mechanism: antibodies that directly inhibit activity of the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, a drug class that includes alirocumab (Praluent) and evolocumab (Repatha). Inclisiran cuts PCSK9 activity by blocking this enzyme’s gene transcription in liver cells thereby interfering with PCSK9 production.

Mitchel L. Zoler/MDedge News

Results from this study, the ORION-3 trial, provide “the first prospective long-term evaluation of the durability and safety of an siRNA-based therapy to provide clinically meaningful reductions in LDL cholesterol with a convenient dosing schedule,” wrote Kausik K. Ray, MD, and coauthors in a report in The Lancet Diabetes & Endocrinology.

The findings “provide assurance that siRNA-based therapies are safe and have the potential to provide a convenient approach to managing” LDL-C, wrote Dr. Ray, a cardiologist and professor of public health at Imperial College London, and his associates.
 

Evolocumab surpasses inclisiran in crossover cohort

The new data from ORION-3 study included findings from 92 patients first treated with evolocumab injections every 2 weeks for a year, an intervention that lowered their LDL-C levels by an average of about 60%, compared with their pretreatment level. ORION-3’s study design then crossed these patients to treatment with injections of inclisiran twice a year during 3 further years of follow-up, during which their average LDL levels reset to a roughly 45% drop from baseline, a potentially clinically meaningful difference, commented Robert S. Rosenson, MD, a lipid management specialist who was not involved in the ORION-3 study.

“This is the first evidence that compared the two classes” within a single study, thereby avoiding a problematic cross-study comparison. “That’s why the data are important. They underscore that the monoclonal antibodies are more effective for lowering LDL-C,” compared with inclisiran, said Dr. Rosenson, professor and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai in New York.

The findings “confirm in a trial that the PCSK9 monoclonal antibodies are indeed more potent,” he said in an interview.

But Dr. Rosenson acknowledged that, while this analysis used data on patients treated with evolocumab and then switched to inclisiran collected prospectively in a single study, it has the limitation of involving a comparison that was not prespecified. The primary goal of the evolocumab-to-inclisiran switch included in ORION-3 was to assess the ease, safety, and efficacy of a switch to inclisiran from treatment with a PCSK9 antibody and was not intended to compare the two drug classes. 

The roughly 15% absolute difference in LDL-C lowering between the two tested drug classes can have substantial clinical implications for patients who start treatment with highly elevated levels of LDL-C, more than 190 mg/dL, because they have heterozygous familial hypercholesterolemia, are unable to take a statin because of intolerance, or both. The difference in LDL-C reduction with an antibody or with inclisiran could mean the difference between whether or not a patient like this achieves their LDL-C goal level, Dr. Rosenson explained.

Inclisiran’s upside

On the other hand, inclisiran has a couple of important advantages. First, its mechanism of action means that effective treatment involves one injection every 6 months following a patient’s first two injections at onset and after 90 days, with all injections administered in a clinician’s office. In contrast, both of the monoclonal antibodies require injections every other week, a schedule that depends on patient self-injections using prefilled syringes obtained from a pharmacy.

Mitchel L. Zoler/MDedge News

Twice-a-year dosing by a clinician can be a major attraction because it helps ensure treatment compliance, aids patients with physical or psychological limitations to self-injection, reduces the pill burden for patients who require multiple medications, and facilitates frequent travelers who would otherwise need to carry syringes with them on trips, Dr. Rosenson noted.

The second big advantage of office-based administration of inclisiran for U.S. Medicare patients is that the treatment is billed under a patient’s part B coverage, usually resulting in easier coverage and a significantly lower patient co-pay, compared with Medicare’s coverage for a pharmacy-dispensed agent, which is covered under Medicare part D. “Part B coverage is financially more doable” for most Medicare patients, said Dr. Rosenson.

The administration schedule for inclisiran as well as its superior Medicare coverage makes the agent “transformative” for LDL-C lowering in patients for whom treatment delivery, frequency, and payment are issues, he said.
 

Inclisiran uptake modest after FDA approval

Despite these pluses, uptake of inclisiran has been modest since it received U.S. marketing approval in December 2021. In its most recent quarterly financial filing, in October 2022, Novartis reported total worldwide income from inclisiran (Leqvio) of $70 million during the first 9 months of 2022, although a Novartis spokesperson noted that the company has seen “positive trends in uptake” over the course of 2022. Inclisiran is labeled as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering” of LDL-C.

During 2022, inclisiran uptake lagged because of the usual problems that slow the introduction of new drugs and new drug classes, especially ones that require dosing by a clinician. Months were spent waiting for billing codes to roll out, for clinical staffs to incorporate inclisiran injections into their routines, and for commercial insurers to get up to speed on their coverage, Dr. Rosenson said.

Also, a key step for widespread uptake of a new medication for improving cardiovascular disease outcomes – results from phase 3 studies that document safety and efficacy for these outcomes – remains several years off. The ORION-4 trial and the VICTORION-2P trial, each assessing the impact of inclisiran on cardiovascular disease events in roughly 15,000 people, will need about another 3-4 years before their results become available.

Professional medical societies that issue cardiovascular-disease management guidelines “prefer agents with proven benefits in phase 3 trials,” Dr. Rosenson noted.

Hence, the most recent update to U.S. LDL-C–management guidelines, released in the second half of 2022 by the American College of Cardiology as an Expert Consensus Decision Pathway, said this about the current role for inclisiran: “At the present time, a PCSK9 monoclonal antibody is preferred as the initial PCSK9 inhibitor of choice in view of its demonstrated safety, efficacy, and benefits for cardiovascular outcomes in the FOURIER [for evolocumab] and ODYSSEY Outcomes [for alirocumab] trials. The ORION-4 and VICTORION-2P cardiovascular outcomes trials with inclisiran are currently underway, and their completion is anticipated in 2026 and 2027, respectively. In view of the twice-yearly dosing regimen, inclisiran may be considered in patients with demonstrated poor adherence to PCSK9 monoclonal antibodies. Patients with adverse effects from both PSCK9 monoclonal antibodies or those who may be unable to self-inject may also be considered for therapy with inclisiran.”
 

ORION-3 extended the ORION-1 trial

The ORION-1 study was a phase 2 placebo-controlled, dose-ranging safety and efficacy assessment of inclisiran that gave patients two injections of the drug, at day zero and 90 days, and followed them for an additional 120 days (210 days total follow-up duration), and in some cases for as long as 360 days total. Of the 370 patients who received inclisiran in ORION-1, 290 agreed to continue inclisiran in the open-label extension, ORION-3. ORION-1 also included 127 patients randomized to initial placebo treatment, and 92 of these patients agreed to continue in ORION-3 and became the patients initially treated with evolocumab injections every other week for 1 year followed by initiation of an inclisiran regimen.

The primary outcome of ORION-3 was the change in LDL-C from baseline (the ORION-1 baseline) after 210 days of receiving inclisiran in ORION-3 (or a total of roughly 570 days after the start of ORION-1). The primary endpoint showed that, at day 210 of ORION-3 the average reduction in LDL-C from the original baseline level was 47.5%.

But a “more important” outcome, said Dr. Ray when he first reported the ORION-3 results during the American Heart Association scientific sessions in Chicago in November 2022, was that, overall, during 4 years on inclisiran this cohort showed an average cut in LDL-C from baseline of about 45% that consistently remained at this level throughout the 4 years of treatment.

“This provides us with an idea of what happens with chronic inclisiran dosing,” Dr. Ray explained. “There was no loss of biological efficacy, and we achieved these clinically meaningful, time-averaged reductions with a good safety profile. The great thing is that when patients get their injections [every 6 months] you see a consistent LDL-C reduction. A twice-annual injection is an opportunity to redesign” the way patients receive preventive cardiology care and treatment to lower LDL-C, Dr Ray said.

ORION-1 was sponsored by The Medicines Company. ORION-3 was sponsored by Novartis (which acquired The Medicines Company). Dr. Ray has received consulting fees, personal fees, and research grants from Novartis, as well as consulting fees and research grants from Amgen, the company that markets evolocumab (Repatha), and research grants from Regeneron, the company that markets alirocumab (Praluent). He has also received consulting fee, personal fees, and research grants from numerous other companies. Dr. Rosenson has been a consultant to and has received research funding from Amgen, Novartis, and Regeneron, and he has received speaking fees from Amgen and Regeneron, and has ties to several other pharmaceutical companies.
 

This article was updated on 1/26/2023.

Patients who received an injection of inclisiran (Leqvio), a small interfering RNA (siRNA) agent, every 6 months for as long as 4 years safely maintained about a 45% reduction from baseline in their level of low-density lipoprotein cholesterol (LDL-C) in an open-label extension study with 382 patients.

In addition to providing the longest reported treatment experience with inclisiran, which received Food and Drug Administration marketing approval a little over a year ago, the results also suggest with the most definitive evidence to date that inclisiran is less effective for lowering LDL-C, compared with a class of medications that reduce LDL-C by a related but distinct mechanism: antibodies that directly inhibit activity of the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, a drug class that includes alirocumab (Praluent) and evolocumab (Repatha). Inclisiran cuts PCSK9 activity by blocking this enzyme’s gene transcription in liver cells thereby interfering with PCSK9 production.

Mitchel L. Zoler/MDedge News

Results from this study, the ORION-3 trial, provide “the first prospective long-term evaluation of the durability and safety of an siRNA-based therapy to provide clinically meaningful reductions in LDL cholesterol with a convenient dosing schedule,” wrote Kausik K. Ray, MD, and coauthors in a report in The Lancet Diabetes & Endocrinology.

The findings “provide assurance that siRNA-based therapies are safe and have the potential to provide a convenient approach to managing” LDL-C, wrote Dr. Ray, a cardiologist and professor of public health at Imperial College London, and his associates.
 

Evolocumab surpasses inclisiran in crossover cohort

The new data from ORION-3 study included findings from 92 patients first treated with evolocumab injections every 2 weeks for a year, an intervention that lowered their LDL-C levels by an average of about 60%, compared with their pretreatment level. ORION-3’s study design then crossed these patients to treatment with injections of inclisiran twice a year during 3 further years of follow-up, during which their average LDL levels reset to a roughly 45% drop from baseline, a potentially clinically meaningful difference, commented Robert S. Rosenson, MD, a lipid management specialist who was not involved in the ORION-3 study.

“This is the first evidence that compared the two classes” within a single study, thereby avoiding a problematic cross-study comparison. “That’s why the data are important. They underscore that the monoclonal antibodies are more effective for lowering LDL-C,” compared with inclisiran, said Dr. Rosenson, professor and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai in New York.

The findings “confirm in a trial that the PCSK9 monoclonal antibodies are indeed more potent,” he said in an interview.

But Dr. Rosenson acknowledged that, while this analysis used data on patients treated with evolocumab and then switched to inclisiran collected prospectively in a single study, it has the limitation of involving a comparison that was not prespecified. The primary goal of the evolocumab-to-inclisiran switch included in ORION-3 was to assess the ease, safety, and efficacy of a switch to inclisiran from treatment with a PCSK9 antibody and was not intended to compare the two drug classes. 

The roughly 15% absolute difference in LDL-C lowering between the two tested drug classes can have substantial clinical implications for patients who start treatment with highly elevated levels of LDL-C, more than 190 mg/dL, because they have heterozygous familial hypercholesterolemia, are unable to take a statin because of intolerance, or both. The difference in LDL-C reduction with an antibody or with inclisiran could mean the difference between whether or not a patient like this achieves their LDL-C goal level, Dr. Rosenson explained.

Inclisiran’s upside

On the other hand, inclisiran has a couple of important advantages. First, its mechanism of action means that effective treatment involves one injection every 6 months following a patient’s first two injections at onset and after 90 days, with all injections administered in a clinician’s office. In contrast, both of the monoclonal antibodies require injections every other week, a schedule that depends on patient self-injections using prefilled syringes obtained from a pharmacy.

Mitchel L. Zoler/MDedge News

Twice-a-year dosing by a clinician can be a major attraction because it helps ensure treatment compliance, aids patients with physical or psychological limitations to self-injection, reduces the pill burden for patients who require multiple medications, and facilitates frequent travelers who would otherwise need to carry syringes with them on trips, Dr. Rosenson noted.

The second big advantage of office-based administration of inclisiran for U.S. Medicare patients is that the treatment is billed under a patient’s part B coverage, usually resulting in easier coverage and a significantly lower patient co-pay, compared with Medicare’s coverage for a pharmacy-dispensed agent, which is covered under Medicare part D. “Part B coverage is financially more doable” for most Medicare patients, said Dr. Rosenson.

The administration schedule for inclisiran as well as its superior Medicare coverage makes the agent “transformative” for LDL-C lowering in patients for whom treatment delivery, frequency, and payment are issues, he said.
 

Inclisiran uptake modest after FDA approval

Despite these pluses, uptake of inclisiran has been modest since it received U.S. marketing approval in December 2021. In its most recent quarterly financial filing, in October 2022, Novartis reported total worldwide income from inclisiran (Leqvio) of $70 million during the first 9 months of 2022, although a Novartis spokesperson noted that the company has seen “positive trends in uptake” over the course of 2022. Inclisiran is labeled as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering” of LDL-C.

During 2022, inclisiran uptake lagged because of the usual problems that slow the introduction of new drugs and new drug classes, especially ones that require dosing by a clinician. Months were spent waiting for billing codes to roll out, for clinical staffs to incorporate inclisiran injections into their routines, and for commercial insurers to get up to speed on their coverage, Dr. Rosenson said.

Also, a key step for widespread uptake of a new medication for improving cardiovascular disease outcomes – results from phase 3 studies that document safety and efficacy for these outcomes – remains several years off. The ORION-4 trial and the VICTORION-2P trial, each assessing the impact of inclisiran on cardiovascular disease events in roughly 15,000 people, will need about another 3-4 years before their results become available.

Professional medical societies that issue cardiovascular-disease management guidelines “prefer agents with proven benefits in phase 3 trials,” Dr. Rosenson noted.

Hence, the most recent update to U.S. LDL-C–management guidelines, released in the second half of 2022 by the American College of Cardiology as an Expert Consensus Decision Pathway, said this about the current role for inclisiran: “At the present time, a PCSK9 monoclonal antibody is preferred as the initial PCSK9 inhibitor of choice in view of its demonstrated safety, efficacy, and benefits for cardiovascular outcomes in the FOURIER [for evolocumab] and ODYSSEY Outcomes [for alirocumab] trials. The ORION-4 and VICTORION-2P cardiovascular outcomes trials with inclisiran are currently underway, and their completion is anticipated in 2026 and 2027, respectively. In view of the twice-yearly dosing regimen, inclisiran may be considered in patients with demonstrated poor adherence to PCSK9 monoclonal antibodies. Patients with adverse effects from both PSCK9 monoclonal antibodies or those who may be unable to self-inject may also be considered for therapy with inclisiran.”
 

ORION-3 extended the ORION-1 trial

The ORION-1 study was a phase 2 placebo-controlled, dose-ranging safety and efficacy assessment of inclisiran that gave patients two injections of the drug, at day zero and 90 days, and followed them for an additional 120 days (210 days total follow-up duration), and in some cases for as long as 360 days total. Of the 370 patients who received inclisiran in ORION-1, 290 agreed to continue inclisiran in the open-label extension, ORION-3. ORION-1 also included 127 patients randomized to initial placebo treatment, and 92 of these patients agreed to continue in ORION-3 and became the patients initially treated with evolocumab injections every other week for 1 year followed by initiation of an inclisiran regimen.

The primary outcome of ORION-3 was the change in LDL-C from baseline (the ORION-1 baseline) after 210 days of receiving inclisiran in ORION-3 (or a total of roughly 570 days after the start of ORION-1). The primary endpoint showed that, at day 210 of ORION-3 the average reduction in LDL-C from the original baseline level was 47.5%.

But a “more important” outcome, said Dr. Ray when he first reported the ORION-3 results during the American Heart Association scientific sessions in Chicago in November 2022, was that, overall, during 4 years on inclisiran this cohort showed an average cut in LDL-C from baseline of about 45% that consistently remained at this level throughout the 4 years of treatment.

“This provides us with an idea of what happens with chronic inclisiran dosing,” Dr. Ray explained. “There was no loss of biological efficacy, and we achieved these clinically meaningful, time-averaged reductions with a good safety profile. The great thing is that when patients get their injections [every 6 months] you see a consistent LDL-C reduction. A twice-annual injection is an opportunity to redesign” the way patients receive preventive cardiology care and treatment to lower LDL-C, Dr Ray said.

ORION-1 was sponsored by The Medicines Company. ORION-3 was sponsored by Novartis (which acquired The Medicines Company). Dr. Ray has received consulting fees, personal fees, and research grants from Novartis, as well as consulting fees and research grants from Amgen, the company that markets evolocumab (Repatha), and research grants from Regeneron, the company that markets alirocumab (Praluent). He has also received consulting fee, personal fees, and research grants from numerous other companies. Dr. Rosenson has been a consultant to and has received research funding from Amgen, Novartis, and Regeneron, and he has received speaking fees from Amgen and Regeneron, and has ties to several other pharmaceutical companies.
 

This article was updated on 1/26/2023.

Patients who received an injection of inclisiran (Leqvio), a small interfering RNA (siRNA) agent, every 6 months for as long as 4 years safely maintained about a 45% reduction from baseline in their level of low-density lipoprotein cholesterol (LDL-C) in an open-label extension study with 382 patients.

In addition to providing the longest reported treatment experience with inclisiran, which received Food and Drug Administration marketing approval a little over a year ago, the results also suggest with the most definitive evidence to date that inclisiran is less effective for lowering LDL-C, compared with a class of medications that reduce LDL-C by a related but distinct mechanism: antibodies that directly inhibit activity of the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, a drug class that includes alirocumab (Praluent) and evolocumab (Repatha). Inclisiran cuts PCSK9 activity by blocking this enzyme’s gene transcription in liver cells thereby interfering with PCSK9 production.

Mitchel L. Zoler/MDedge News

Results from this study, the ORION-3 trial, provide “the first prospective long-term evaluation of the durability and safety of an siRNA-based therapy to provide clinically meaningful reductions in LDL cholesterol with a convenient dosing schedule,” wrote Kausik K. Ray, MD, and coauthors in a report in The Lancet Diabetes & Endocrinology.

The findings “provide assurance that siRNA-based therapies are safe and have the potential to provide a convenient approach to managing” LDL-C, wrote Dr. Ray, a cardiologist and professor of public health at Imperial College London, and his associates.
 

Evolocumab surpasses inclisiran in crossover cohort

The new data from ORION-3 study included findings from 92 patients first treated with evolocumab injections every 2 weeks for a year, an intervention that lowered their LDL-C levels by an average of about 60%, compared with their pretreatment level. ORION-3’s study design then crossed these patients to treatment with injections of inclisiran twice a year during 3 further years of follow-up, during which their average LDL levels reset to a roughly 45% drop from baseline, a potentially clinically meaningful difference, commented Robert S. Rosenson, MD, a lipid management specialist who was not involved in the ORION-3 study.

“This is the first evidence that compared the two classes” within a single study, thereby avoiding a problematic cross-study comparison. “That’s why the data are important. They underscore that the monoclonal antibodies are more effective for lowering LDL-C,” compared with inclisiran, said Dr. Rosenson, professor and director of cardiometabolic disorders at the Icahn School of Medicine at Mount Sinai in New York.

The findings “confirm in a trial that the PCSK9 monoclonal antibodies are indeed more potent,” he said in an interview.

But Dr. Rosenson acknowledged that, while this analysis used data on patients treated with evolocumab and then switched to inclisiran collected prospectively in a single study, it has the limitation of involving a comparison that was not prespecified. The primary goal of the evolocumab-to-inclisiran switch included in ORION-3 was to assess the ease, safety, and efficacy of a switch to inclisiran from treatment with a PCSK9 antibody and was not intended to compare the two drug classes. 

The roughly 15% absolute difference in LDL-C lowering between the two tested drug classes can have substantial clinical implications for patients who start treatment with highly elevated levels of LDL-C, more than 190 mg/dL, because they have heterozygous familial hypercholesterolemia, are unable to take a statin because of intolerance, or both. The difference in LDL-C reduction with an antibody or with inclisiran could mean the difference between whether or not a patient like this achieves their LDL-C goal level, Dr. Rosenson explained.

Inclisiran’s upside

On the other hand, inclisiran has a couple of important advantages. First, its mechanism of action means that effective treatment involves one injection every 6 months following a patient’s first two injections at onset and after 90 days, with all injections administered in a clinician’s office. In contrast, both of the monoclonal antibodies require injections every other week, a schedule that depends on patient self-injections using prefilled syringes obtained from a pharmacy.

Mitchel L. Zoler/MDedge News

Twice-a-year dosing by a clinician can be a major attraction because it helps ensure treatment compliance, aids patients with physical or psychological limitations to self-injection, reduces the pill burden for patients who require multiple medications, and facilitates frequent travelers who would otherwise need to carry syringes with them on trips, Dr. Rosenson noted.

The second big advantage of office-based administration of inclisiran for U.S. Medicare patients is that the treatment is billed under a patient’s part B coverage, usually resulting in easier coverage and a significantly lower patient co-pay, compared with Medicare’s coverage for a pharmacy-dispensed agent, which is covered under Medicare part D. “Part B coverage is financially more doable” for most Medicare patients, said Dr. Rosenson.

The administration schedule for inclisiran as well as its superior Medicare coverage makes the agent “transformative” for LDL-C lowering in patients for whom treatment delivery, frequency, and payment are issues, he said.
 

Inclisiran uptake modest after FDA approval

Despite these pluses, uptake of inclisiran has been modest since it received U.S. marketing approval in December 2021. In its most recent quarterly financial filing, in October 2022, Novartis reported total worldwide income from inclisiran (Leqvio) of $70 million during the first 9 months of 2022, although a Novartis spokesperson noted that the company has seen “positive trends in uptake” over the course of 2022. Inclisiran is labeled as an “adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional lowering” of LDL-C.

During 2022, inclisiran uptake lagged because of the usual problems that slow the introduction of new drugs and new drug classes, especially ones that require dosing by a clinician. Months were spent waiting for billing codes to roll out, for clinical staffs to incorporate inclisiran injections into their routines, and for commercial insurers to get up to speed on their coverage, Dr. Rosenson said.

Also, a key step for widespread uptake of a new medication for improving cardiovascular disease outcomes – results from phase 3 studies that document safety and efficacy for these outcomes – remains several years off. The ORION-4 trial and the VICTORION-2P trial, each assessing the impact of inclisiran on cardiovascular disease events in roughly 15,000 people, will need about another 3-4 years before their results become available.

Professional medical societies that issue cardiovascular-disease management guidelines “prefer agents with proven benefits in phase 3 trials,” Dr. Rosenson noted.

Hence, the most recent update to U.S. LDL-C–management guidelines, released in the second half of 2022 by the American College of Cardiology as an Expert Consensus Decision Pathway, said this about the current role for inclisiran: “At the present time, a PCSK9 monoclonal antibody is preferred as the initial PCSK9 inhibitor of choice in view of its demonstrated safety, efficacy, and benefits for cardiovascular outcomes in the FOURIER [for evolocumab] and ODYSSEY Outcomes [for alirocumab] trials. The ORION-4 and VICTORION-2P cardiovascular outcomes trials with inclisiran are currently underway, and their completion is anticipated in 2026 and 2027, respectively. In view of the twice-yearly dosing regimen, inclisiran may be considered in patients with demonstrated poor adherence to PCSK9 monoclonal antibodies. Patients with adverse effects from both PSCK9 monoclonal antibodies or those who may be unable to self-inject may also be considered for therapy with inclisiran.”
 

ORION-3 extended the ORION-1 trial

The ORION-1 study was a phase 2 placebo-controlled, dose-ranging safety and efficacy assessment of inclisiran that gave patients two injections of the drug, at day zero and 90 days, and followed them for an additional 120 days (210 days total follow-up duration), and in some cases for as long as 360 days total. Of the 370 patients who received inclisiran in ORION-1, 290 agreed to continue inclisiran in the open-label extension, ORION-3. ORION-1 also included 127 patients randomized to initial placebo treatment, and 92 of these patients agreed to continue in ORION-3 and became the patients initially treated with evolocumab injections every other week for 1 year followed by initiation of an inclisiran regimen.

The primary outcome of ORION-3 was the change in LDL-C from baseline (the ORION-1 baseline) after 210 days of receiving inclisiran in ORION-3 (or a total of roughly 570 days after the start of ORION-1). The primary endpoint showed that, at day 210 of ORION-3 the average reduction in LDL-C from the original baseline level was 47.5%.

But a “more important” outcome, said Dr. Ray when he first reported the ORION-3 results during the American Heart Association scientific sessions in Chicago in November 2022, was that, overall, during 4 years on inclisiran this cohort showed an average cut in LDL-C from baseline of about 45% that consistently remained at this level throughout the 4 years of treatment.

“This provides us with an idea of what happens with chronic inclisiran dosing,” Dr. Ray explained. “There was no loss of biological efficacy, and we achieved these clinically meaningful, time-averaged reductions with a good safety profile. The great thing is that when patients get their injections [every 6 months] you see a consistent LDL-C reduction. A twice-annual injection is an opportunity to redesign” the way patients receive preventive cardiology care and treatment to lower LDL-C, Dr Ray said.

ORION-1 was sponsored by The Medicines Company. ORION-3 was sponsored by Novartis (which acquired The Medicines Company). Dr. Ray has received consulting fees, personal fees, and research grants from Novartis, as well as consulting fees and research grants from Amgen, the company that markets evolocumab (Repatha), and research grants from Regeneron, the company that markets alirocumab (Praluent). He has also received consulting fee, personal fees, and research grants from numerous other companies. Dr. Rosenson has been a consultant to and has received research funding from Amgen, Novartis, and Regeneron, and he has received speaking fees from Amgen and Regeneron, and has ties to several other pharmaceutical companies.
 

This article was updated on 1/26/2023.

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

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

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

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

A new study that quantifies the harm to the liver of eating fast food might motivate people to eat less of it – especially those with obesity or diabetes.

The study finds that getting one-fifth or more of total daily calories from fast food can increase the risk of nonalcoholic fatty liver disease, which can lead to cirrhosis and its complications, including liver failure and liver cancer.

Annbozhko/iStock/Getty Images

Although the magnitude of association was modest among the general population, “striking” elevations in steatosis were evident among persons with obesity and diabetes who consumed fast food, in comparison with their counterparts who did not have obesity and diabetes, the researchers reported.

“My hope is that this study encourages people to seek out more nutritious, healthy food options and provides information that clinicians can use to counsel their patients, particularly those with underlying metabolic risk factors, of the importance of avoiding foods that are high in fat, carbohydrates, and processed sugars,” lead investigator Ani Kardashian, MD, hepatologist with the University of Southern California, Los Angeles, said in an interview.

“At a policy level, public health efforts are needed to improve access to affordable, healthy, and nutritious food options across the U.S. This is especially important as more people have turned to fast foods during the pandemic and as the price of food as risen dramatically over the past year due to food inflation,” Dr. Kardashian added.

The study was published online in Clinical Gastroenterology and Hepatology.
 

More fast food, greater steatosis

The findings are based on data from 3,954 adults who participated in the National Health and Nutrition Examination Survey (NHANES) of 2017-2018 and who underwent vibration-controlled transient elastography. Of these participants, data regarding 1- or 2-day dietary recall were available.

Steatosis, the primary outcome, was measured via controlled attenuation parameter (CAP). Two validated cutoffs were utilized (CAP ≥ 263 dB/m and CAP ≥ 285 dB/m).

Of those surveyed, 52% consumed any fast food, and 29% derived 20% or more of their daily calories from fast food.

Fast-food intake of 20% or more of daily calories was significantly associated with greater steatosis after multivariable adjustment, both as a continuous measure (4.6 dB/m higher CAP score) and with respect to the CAP ≥ 263 dB/m cutoff (odds ratio [OR], 1.45).

“The negative effects are particularly severe in people who already have diabetes and obesity,” Dr. Kardashian told this news organization.

For example, with diabetes and fast-food intake of 20% or more of daily calories, the ORs of meeting the CAP ≥ 263 dB/m cutoff and the CAP ≥ 285 dB/m cutoff were 2.3 and 2.48, respectively.

The researchers said their findings are particularly “alarming,” given the overall increase in fast-food consumption over the past 50 years in the United States, regardless of socioeconomic status.
 

Diet coaching

The finding that fast food has more deleterious impact on those with obesity and diabetes “emphasizes that it is not just one insult but multiple factors that contribute to overall health,” said Nancy Reau, MD, section chief of hepatology at Rush University Medical Center in Chicago.

“This is actually great news, because diet is modifiable, vs. your genetics, which you currently can’t change. This doesn’t mean if you’re lean you can eat whatever you want, but if you are overweight, being careful with your diet does have impact, even if it doesn’t lead to substantial weight changes,” said Dr. Reau, who is not affiliated with the study.

For people who have limited options and need to eat fast food, “there are healthy choices at most restaurants; you just need to be smart about reading labels, watching calories, and ordering the healthier options,” Dr. Reau said in an interview.

Fast food and fatty liver go “hand in hand,” Lisa Ganjhu, DO, gastroenterologist and hepatologist at NYU Langone Health in New York, told this news organization.

“I counsel and coach my patients on healthy diet and exercise, and I’ve been pretty successful,” said Dr. Ganjhu, who was not involved with the study.

“If my patient is eating at McDonald’s a lot, I basically walk through the menu with them and help them find something healthy. When patients see the benefits of cutting out fat and reducing carbohydrates, they are more apt to continue,” Dr. Ganjhu said.

The study was funded by the University of Southern California. Dr. Kardashian, Dr. Reau, and Dr. Ganjhu have disclosed no relevant financial relationships.

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

Hormone replacement therapy (HRT) introduced early during the menopausal transition may protect against Alzheimer’s dementia in women carrying the APOE4 gene, new research suggests.

Results from a cohort study of almost 1,200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes – areas that are affected early by Alzheimer’s disease (AD) pathology.

HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause.

“Clinicians are very much aware of the susceptibility of women to cognitive disturbances during menopause,” lead author Rasha Saleh, MD, senior research associate, University of East Anglia (England), said in an interview.

“Identifying the at-risk APOE4 women and early HRT introduction can be of benefit. Confirming our findings in a clinical trial would be the next step forward,” Dr. Saleh said.

The findings were published online in Alzheimer’s Research and Therapy.
 

Personalized approaches

Dr. Saleh noted that estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.

“The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology,” she said.

HRT during the menopausal transition and afterward is “being considered as a strategy to mitigate cognitive decline,” the investigators wrote. Early observational studies have suggested that oral estrogen “may be protective against dementia,” but results of clinical trials have been inconsistent, and some have even shown “harmful effects.”

The current researchers were “interested in the personalized approaches in the prevention of AD,” Dr. Saleh said. Preclinical and pilot data from her group have shown that women with APOE4 have “better cognitive test scores with nutritional and hormonal interventions.”

This led Dr. Saleh to hypothesize that HRT would be of more cognitive benefit for those with versus without APOE4, particularly when introduced early during the menopausal transition.

To investigate this hypothesis, the researchers analyzed baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.

Participants were recruited from 10 European countries. All were required to be at least 50 years old, to have not been diagnosed with dementia at baseline, and to have no medical or psychiatric illness that could potentially exclude them from further research.

The current study included 1,178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT treatment for current or previous users included estrogen alone or estrogen plus progestogens via oral or transdermal administration routes, and at different doses.

The four tests used to assess cognition were the Mini-Mental State Examination dot counting to evaluate verbal working memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score, the Four Mountain Test, and the supermarket trolley virtual reality test.

Brain MRI data were collected. The researchers focused on the medial temporal lobe as the “main brain region regulating cognition and memory processing.” This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.
 

‘Critical window’

The researchers found a “trend” toward an APOE-HRT interaction (P-interaction = .097) for the total RBANS score. In particular, it was significant for the RBANS delayed memory index, where scores were consistently higher for women with APOE4 who had received HRT, compared with all other groups (P-interaction = .009).

Within-genotype group comparisons showed that HRT users had a higher RBANS total scale score and delayed memory index (P = .045 and P = .002, respectively), but only among APOE4 carriers. Effect size analyses showed a large effect of HRT use on the Four Mountain Test score and the supermarket trolley virtual reality test score (Cohen’s d = 0.988 and 1.2, respectively).

“This large effect was found only in APOE4 carriers,” the investigators noted.

Similarly, a moderate to large effect of HRT on the left entorhinal volume was observed in APOE4 carriers (Cohen’s d = 0.63).

In members of the APOE4 group who received HRT, the left entorhinal and left and right amygdala volumes were larger, compared with both no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the right entorhinal volume (P = .074).

In addition, among HRT users, the left entorhinal volume was larger (P = .03); the right and left anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the left superior frontal gyrus volume was larger (P = .009) in comparison with women who did not receive HRT, independently of their APOE genotype.

Early use of HRT among APOE4 carriers was associated with larger right and left hippocampal volume (P = .035 and P = .028, respectively) – an association not found in non-APOE4 carriers. The association was also not significant when participants were not stratified by APOE genotype.

“The key important point here is the timing, or the ‘critical window,’ when HRT can be of most benefit,” Dr. Saleh said. “This is most beneficial when introduced early, before the neuropathology becomes irreversible.”

Study limitations include its cross-sectional design, which precludes the establishment of a causal relationship, and the fact that information regarding the type and dose of estrogen was not available for all participants.

HRT is not without risk, Dr. Saleh noted. She recommended that clinicians “carry out various screening tests to make sure that a woman is eligible for HRT and not at risk of hypercoagulability, for instance.”
 

Risk-benefit ratio

In a comment, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, called the study “exactly the kind of work that needs to be done.”

Dr. Fillit, who was not involved with the current research, is a clinical professor of geriatric medicine, palliative care medicine, and neuroscience at Mount Sinai Hospital, New York.

He compared the process with that of osteoporosis. “We know that if women are treated [with HRT] at the time of the menopause, you can prevent the rapid bone loss that occurs with rapid estrogen loss. But if you wait 5, 10 years out, once the bone loss has occurred, the HRT doesn’t really have any impact on osteoporosis risk because the horse is already out of the barn,” he said.

Although HRT carries risks, “they can clearly be managed; and if it’s proven that estrogen or hormone replacement around the time of the menopause can be protective [against AD], the risk-benefit ratio of HRT could be in favor of treatment,” Dr. Fillit added.

The study was conducted as part of the Medical Research Council NuBrain Consortium. The investigators and Dr. Fillit reported no relevant financial relationships.

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

Hormone replacement therapy (HRT) introduced early during the menopausal transition may protect against Alzheimer’s dementia in women carrying the APOE4 gene, new research suggests.

Results from a cohort study of almost 1,200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes – areas that are affected early by Alzheimer’s disease (AD) pathology.

HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause.

“Clinicians are very much aware of the susceptibility of women to cognitive disturbances during menopause,” lead author Rasha Saleh, MD, senior research associate, University of East Anglia (England), said in an interview.

“Identifying the at-risk APOE4 women and early HRT introduction can be of benefit. Confirming our findings in a clinical trial would be the next step forward,” Dr. Saleh said.

The findings were published online in Alzheimer’s Research and Therapy.
 

Personalized approaches

Dr. Saleh noted that estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.

“The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology,” she said.

HRT during the menopausal transition and afterward is “being considered as a strategy to mitigate cognitive decline,” the investigators wrote. Early observational studies have suggested that oral estrogen “may be protective against dementia,” but results of clinical trials have been inconsistent, and some have even shown “harmful effects.”

The current researchers were “interested in the personalized approaches in the prevention of AD,” Dr. Saleh said. Preclinical and pilot data from her group have shown that women with APOE4 have “better cognitive test scores with nutritional and hormonal interventions.”

This led Dr. Saleh to hypothesize that HRT would be of more cognitive benefit for those with versus without APOE4, particularly when introduced early during the menopausal transition.

To investigate this hypothesis, the researchers analyzed baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.

Participants were recruited from 10 European countries. All were required to be at least 50 years old, to have not been diagnosed with dementia at baseline, and to have no medical or psychiatric illness that could potentially exclude them from further research.

The current study included 1,178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT treatment for current or previous users included estrogen alone or estrogen plus progestogens via oral or transdermal administration routes, and at different doses.

The four tests used to assess cognition were the Mini-Mental State Examination dot counting to evaluate verbal working memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score, the Four Mountain Test, and the supermarket trolley virtual reality test.

Brain MRI data were collected. The researchers focused on the medial temporal lobe as the “main brain region regulating cognition and memory processing.” This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.
 

‘Critical window’

The researchers found a “trend” toward an APOE-HRT interaction (P-interaction = .097) for the total RBANS score. In particular, it was significant for the RBANS delayed memory index, where scores were consistently higher for women with APOE4 who had received HRT, compared with all other groups (P-interaction = .009).

Within-genotype group comparisons showed that HRT users had a higher RBANS total scale score and delayed memory index (P = .045 and P = .002, respectively), but only among APOE4 carriers. Effect size analyses showed a large effect of HRT use on the Four Mountain Test score and the supermarket trolley virtual reality test score (Cohen’s d = 0.988 and 1.2, respectively).

“This large effect was found only in APOE4 carriers,” the investigators noted.

Similarly, a moderate to large effect of HRT on the left entorhinal volume was observed in APOE4 carriers (Cohen’s d = 0.63).

In members of the APOE4 group who received HRT, the left entorhinal and left and right amygdala volumes were larger, compared with both no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the right entorhinal volume (P = .074).

In addition, among HRT users, the left entorhinal volume was larger (P = .03); the right and left anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the left superior frontal gyrus volume was larger (P = .009) in comparison with women who did not receive HRT, independently of their APOE genotype.

Early use of HRT among APOE4 carriers was associated with larger right and left hippocampal volume (P = .035 and P = .028, respectively) – an association not found in non-APOE4 carriers. The association was also not significant when participants were not stratified by APOE genotype.

“The key important point here is the timing, or the ‘critical window,’ when HRT can be of most benefit,” Dr. Saleh said. “This is most beneficial when introduced early, before the neuropathology becomes irreversible.”

Study limitations include its cross-sectional design, which precludes the establishment of a causal relationship, and the fact that information regarding the type and dose of estrogen was not available for all participants.

HRT is not without risk, Dr. Saleh noted. She recommended that clinicians “carry out various screening tests to make sure that a woman is eligible for HRT and not at risk of hypercoagulability, for instance.”
 

Risk-benefit ratio

In a comment, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, called the study “exactly the kind of work that needs to be done.”

Dr. Fillit, who was not involved with the current research, is a clinical professor of geriatric medicine, palliative care medicine, and neuroscience at Mount Sinai Hospital, New York.

He compared the process with that of osteoporosis. “We know that if women are treated [with HRT] at the time of the menopause, you can prevent the rapid bone loss that occurs with rapid estrogen loss. But if you wait 5, 10 years out, once the bone loss has occurred, the HRT doesn’t really have any impact on osteoporosis risk because the horse is already out of the barn,” he said.

Although HRT carries risks, “they can clearly be managed; and if it’s proven that estrogen or hormone replacement around the time of the menopause can be protective [against AD], the risk-benefit ratio of HRT could be in favor of treatment,” Dr. Fillit added.

The study was conducted as part of the Medical Research Council NuBrain Consortium. The investigators and Dr. Fillit reported no relevant financial relationships.

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

Hormone replacement therapy (HRT) introduced early during the menopausal transition may protect against Alzheimer’s dementia in women carrying the APOE4 gene, new research suggests.

Results from a cohort study of almost 1,200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes – areas that are affected early by Alzheimer’s disease (AD) pathology.

HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause.

“Clinicians are very much aware of the susceptibility of women to cognitive disturbances during menopause,” lead author Rasha Saleh, MD, senior research associate, University of East Anglia (England), said in an interview.

“Identifying the at-risk APOE4 women and early HRT introduction can be of benefit. Confirming our findings in a clinical trial would be the next step forward,” Dr. Saleh said.

The findings were published online in Alzheimer’s Research and Therapy.
 

Personalized approaches

Dr. Saleh noted that estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.

“The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology,” she said.

HRT during the menopausal transition and afterward is “being considered as a strategy to mitigate cognitive decline,” the investigators wrote. Early observational studies have suggested that oral estrogen “may be protective against dementia,” but results of clinical trials have been inconsistent, and some have even shown “harmful effects.”

The current researchers were “interested in the personalized approaches in the prevention of AD,” Dr. Saleh said. Preclinical and pilot data from her group have shown that women with APOE4 have “better cognitive test scores with nutritional and hormonal interventions.”

This led Dr. Saleh to hypothesize that HRT would be of more cognitive benefit for those with versus without APOE4, particularly when introduced early during the menopausal transition.

To investigate this hypothesis, the researchers analyzed baseline data from participants in the European Prevention of Alzheimer’s Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.

Participants were recruited from 10 European countries. All were required to be at least 50 years old, to have not been diagnosed with dementia at baseline, and to have no medical or psychiatric illness that could potentially exclude them from further research.

The current study included 1,178 women (mean age, 65.1 years), who were divided by genotype into non-APOE4 and APOE4 groups. HRT treatment for current or previous users included estrogen alone or estrogen plus progestogens via oral or transdermal administration routes, and at different doses.

The four tests used to assess cognition were the Mini-Mental State Examination dot counting to evaluate verbal working memory, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score, the Four Mountain Test, and the supermarket trolley virtual reality test.

Brain MRI data were collected. The researchers focused on the medial temporal lobe as the “main brain region regulating cognition and memory processing.” This lobe includes the hippocampus, the parahippocampus, the entorhinal cortex, and the amygdala.
 

‘Critical window’

The researchers found a “trend” toward an APOE-HRT interaction (P-interaction = .097) for the total RBANS score. In particular, it was significant for the RBANS delayed memory index, where scores were consistently higher for women with APOE4 who had received HRT, compared with all other groups (P-interaction = .009).

Within-genotype group comparisons showed that HRT users had a higher RBANS total scale score and delayed memory index (P = .045 and P = .002, respectively), but only among APOE4 carriers. Effect size analyses showed a large effect of HRT use on the Four Mountain Test score and the supermarket trolley virtual reality test score (Cohen’s d = 0.988 and 1.2, respectively).

“This large effect was found only in APOE4 carriers,” the investigators noted.

Similarly, a moderate to large effect of HRT on the left entorhinal volume was observed in APOE4 carriers (Cohen’s d = 0.63).

In members of the APOE4 group who received HRT, the left entorhinal and left and right amygdala volumes were larger, compared with both no-APOE4 and non-HRT users (P-interaction = .002, .003, and .005, respectively). Similar trends were observed for the right entorhinal volume (P = .074).

In addition, among HRT users, the left entorhinal volume was larger (P = .03); the right and left anterior cingulate gyrus volumes were smaller (P = .003 and .062, respectively); and the left superior frontal gyrus volume was larger (P = .009) in comparison with women who did not receive HRT, independently of their APOE genotype.

Early use of HRT among APOE4 carriers was associated with larger right and left hippocampal volume (P = .035 and P = .028, respectively) – an association not found in non-APOE4 carriers. The association was also not significant when participants were not stratified by APOE genotype.

“The key important point here is the timing, or the ‘critical window,’ when HRT can be of most benefit,” Dr. Saleh said. “This is most beneficial when introduced early, before the neuropathology becomes irreversible.”

Study limitations include its cross-sectional design, which precludes the establishment of a causal relationship, and the fact that information regarding the type and dose of estrogen was not available for all participants.

HRT is not without risk, Dr. Saleh noted. She recommended that clinicians “carry out various screening tests to make sure that a woman is eligible for HRT and not at risk of hypercoagulability, for instance.”
 

Risk-benefit ratio

In a comment, Howard Fillit, MD, cofounder and chief science officer at the Alzheimer’s Drug Discovery Foundation, called the study “exactly the kind of work that needs to be done.”

Dr. Fillit, who was not involved with the current research, is a clinical professor of geriatric medicine, palliative care medicine, and neuroscience at Mount Sinai Hospital, New York.

He compared the process with that of osteoporosis. “We know that if women are treated [with HRT] at the time of the menopause, you can prevent the rapid bone loss that occurs with rapid estrogen loss. But if you wait 5, 10 years out, once the bone loss has occurred, the HRT doesn’t really have any impact on osteoporosis risk because the horse is already out of the barn,” he said.

Although HRT carries risks, “they can clearly be managed; and if it’s proven that estrogen or hormone replacement around the time of the menopause can be protective [against AD], the risk-benefit ratio of HRT could be in favor of treatment,” Dr. Fillit added.

The study was conducted as part of the Medical Research Council NuBrain Consortium. The investigators and Dr. Fillit reported no relevant financial relationships.

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

People who are overweight or have obesity appear to show a blunted response to vitamin D supplementation compared with normal-weight individuals in a new analysis of a randomized trial.

“There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated body mass index (BMI),” said first author Deirdre K. Tobias, ScD, an associate epidemiologist at Brigham and Women’s Hospital’s division of preventive medicine in Boston. She made the comments in a press statement issued with the study, published online in JAMA Network Open.

The findings are from a post hoc analysis of the large-scale Vitamin D and Omega-3 Trial (VITAL), which overall, showed no benefits among those randomized to 5 years of vitamin D supplementation (2,000 IU/day) versus placebo in terms of the primary endpoints of cancer or major cardiovascular disease outcomes.

However, prespecified secondary analyses according to body weight showed that those of normal weight (body mass index < 25.0 kg/m²) did have significant benefits from supplementation versus placebo in terms of cancer incidence (24% lower), cancer mortality (42% lower), and autoimmune disease (22% lower), while no corresponding benefits were observed among those who were overweight or had obesity.

The new analysis adds important context to the trial’s overall findings, noted Katherine N. Bachmann, MD, in an accompanying editorial.

“Thanks to its very large sample size and detailed biomarker analyses, the current study is able to provide novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity, and that this may contribute to the differential outcomes by BMI noted in the original VITAL,” she wrote.

“Further studies are warranted to determine the optimal dose or circulating vitamin D level for individuals with obesity for nonskeletal health-related outcomes,” added Dr. Bachmann, division of diabetes, endocrinology, and metabolism at Vanderbilt University Medical Center, Nashville, Tenn.
 

New analysis examined vitamin D and biomarkers at baseline and 2 years

To take a closer look at the specific changes in vitamin D serum and biomarker levels between the different body-weight groups, Dr. Tobias and colleagues evaluated data from 16,515 participants in the trial (of the 25,000 originally included in VITAL) and looked at changes in key vitamin D serum levels and biomarkers at baseline and follow-up.

Consistent with common observations of lower vitamin D levels with obesity, participants in the higher BMI categories had incrementally lower mean levels of serum total 25-hydroxyvitamin D (25-OHD) prior to randomization, with levels ranging from 32.3 ng/mL for normal weight individuals to 28.0 ng/mL for those with obesity class II (P < .001 for a linear trend).

Baseline levels of other vitamin D biomarkers were also lower with higher BMI, including total 25-OHD 3, free vitamin D (FVD), and bioavailable vitamin D (BioD).

Among 2,742 participants with repeated blood collections at year 2, significant mean increases were observed overall at the end of the study period in serum 25-OHD levels (11.9 ng/mL) among those randomized to vitamin D supplementation, compared with little change in the placebo group (–0.7 ng/mL).

There were also significant increases, overall, in mean total 25-OHD, 25-OHD3, FVD, and BioD levels at 2 years among those receiving supplementation, with little or no change in the placebo group.

When stratified by BMI level, however, the magnitude of increase was lower among those with higher baseline BMI (all treatment effect interactions P < .001). For instance, the mean increases in total 25-OHD level at 2 years for supplementation versus placebo were 13.5 ng/mL for those with a BMI less than 25.0 versus only 10.0 ng/mL for those with a BMI of at least 35.0.

Importantly, even after controlling for baseline vitamin D status of sufficiency or insufficiency, BMI was still significantly associated with changes seen with supplementation.

“It was surprising that, even in the context of low vitamin D levels, those with higher BMI still had a blunted response to supplementation, suggesting the interaction between supplementation and BMI with health outcomes is not simply due to higher prevalence of deficiency,” Dr. Tobias said in an interview. “It really does seem that, even with insufficient or low levels at baseline, those with higher BMI are not able to catch up to sufficient levels as well as those with normal BMI.”
 

Mechanisms?

Among leading theories as to why higher BMI would be associated with lower serum vitamin D levels and a lower response to supplementation is that because vitamin D is a fat-soluble vitamin, the increased adiposity and fat storage capacity with higher BMI results in greater removal of the vitamin from circulation.

“Our results are largely consistent with this hypothesis,” the authors noted.

They added that weight-loss studies, including those involving bariatric surgery, have further shown greater increases in serum 25-OHD or circulating vitamin D levels after weight loss compared with baseline.

Other theories suggest that obesity-induced hepatic dysfunction can contribute to impaired vitamin D metabolism.

Without a clear understanding of the exact mechanisms, the potential for addressing the lower vitamin D levels with, for instance, higher doses of supplementation among those with obesity, also remains unclear, Dr. Tobias noted.

“I think once there’s more clarity on what the mechanism is, then it would make sense to consider what doses could be necessary to achieve the internal levels desired,” she said.

The VITAL study received funding from a grant from the National Center for Complementary and Integrative Health and other sources.

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

People who are overweight or have obesity appear to show a blunted response to vitamin D supplementation compared with normal-weight individuals in a new analysis of a randomized trial.

“There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated body mass index (BMI),” said first author Deirdre K. Tobias, ScD, an associate epidemiologist at Brigham and Women’s Hospital’s division of preventive medicine in Boston. She made the comments in a press statement issued with the study, published online in JAMA Network Open.

The findings are from a post hoc analysis of the large-scale Vitamin D and Omega-3 Trial (VITAL), which overall, showed no benefits among those randomized to 5 years of vitamin D supplementation (2,000 IU/day) versus placebo in terms of the primary endpoints of cancer or major cardiovascular disease outcomes.

However, prespecified secondary analyses according to body weight showed that those of normal weight (body mass index < 25.0 kg/m²) did have significant benefits from supplementation versus placebo in terms of cancer incidence (24% lower), cancer mortality (42% lower), and autoimmune disease (22% lower), while no corresponding benefits were observed among those who were overweight or had obesity.

The new analysis adds important context to the trial’s overall findings, noted Katherine N. Bachmann, MD, in an accompanying editorial.

“Thanks to its very large sample size and detailed biomarker analyses, the current study is able to provide novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity, and that this may contribute to the differential outcomes by BMI noted in the original VITAL,” she wrote.

“Further studies are warranted to determine the optimal dose or circulating vitamin D level for individuals with obesity for nonskeletal health-related outcomes,” added Dr. Bachmann, division of diabetes, endocrinology, and metabolism at Vanderbilt University Medical Center, Nashville, Tenn.
 

New analysis examined vitamin D and biomarkers at baseline and 2 years

To take a closer look at the specific changes in vitamin D serum and biomarker levels between the different body-weight groups, Dr. Tobias and colleagues evaluated data from 16,515 participants in the trial (of the 25,000 originally included in VITAL) and looked at changes in key vitamin D serum levels and biomarkers at baseline and follow-up.

Consistent with common observations of lower vitamin D levels with obesity, participants in the higher BMI categories had incrementally lower mean levels of serum total 25-hydroxyvitamin D (25-OHD) prior to randomization, with levels ranging from 32.3 ng/mL for normal weight individuals to 28.0 ng/mL for those with obesity class II (P < .001 for a linear trend).

Baseline levels of other vitamin D biomarkers were also lower with higher BMI, including total 25-OHD 3, free vitamin D (FVD), and bioavailable vitamin D (BioD).

Among 2,742 participants with repeated blood collections at year 2, significant mean increases were observed overall at the end of the study period in serum 25-OHD levels (11.9 ng/mL) among those randomized to vitamin D supplementation, compared with little change in the placebo group (–0.7 ng/mL).

There were also significant increases, overall, in mean total 25-OHD, 25-OHD3, FVD, and BioD levels at 2 years among those receiving supplementation, with little or no change in the placebo group.

When stratified by BMI level, however, the magnitude of increase was lower among those with higher baseline BMI (all treatment effect interactions P < .001). For instance, the mean increases in total 25-OHD level at 2 years for supplementation versus placebo were 13.5 ng/mL for those with a BMI less than 25.0 versus only 10.0 ng/mL for those with a BMI of at least 35.0.

Importantly, even after controlling for baseline vitamin D status of sufficiency or insufficiency, BMI was still significantly associated with changes seen with supplementation.

“It was surprising that, even in the context of low vitamin D levels, those with higher BMI still had a blunted response to supplementation, suggesting the interaction between supplementation and BMI with health outcomes is not simply due to higher prevalence of deficiency,” Dr. Tobias said in an interview. “It really does seem that, even with insufficient or low levels at baseline, those with higher BMI are not able to catch up to sufficient levels as well as those with normal BMI.”
 

Mechanisms?

Among leading theories as to why higher BMI would be associated with lower serum vitamin D levels and a lower response to supplementation is that because vitamin D is a fat-soluble vitamin, the increased adiposity and fat storage capacity with higher BMI results in greater removal of the vitamin from circulation.

“Our results are largely consistent with this hypothesis,” the authors noted.

They added that weight-loss studies, including those involving bariatric surgery, have further shown greater increases in serum 25-OHD or circulating vitamin D levels after weight loss compared with baseline.

Other theories suggest that obesity-induced hepatic dysfunction can contribute to impaired vitamin D metabolism.

Without a clear understanding of the exact mechanisms, the potential for addressing the lower vitamin D levels with, for instance, higher doses of supplementation among those with obesity, also remains unclear, Dr. Tobias noted.

“I think once there’s more clarity on what the mechanism is, then it would make sense to consider what doses could be necessary to achieve the internal levels desired,” she said.

The VITAL study received funding from a grant from the National Center for Complementary and Integrative Health and other sources.

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

People who are overweight or have obesity appear to show a blunted response to vitamin D supplementation compared with normal-weight individuals in a new analysis of a randomized trial.

“There seems to be something different happening with vitamin D metabolism at higher body weights, and this study may help explain diminished outcomes of supplementation for individuals with an elevated body mass index (BMI),” said first author Deirdre K. Tobias, ScD, an associate epidemiologist at Brigham and Women’s Hospital’s division of preventive medicine in Boston. She made the comments in a press statement issued with the study, published online in JAMA Network Open.

The findings are from a post hoc analysis of the large-scale Vitamin D and Omega-3 Trial (VITAL), which overall, showed no benefits among those randomized to 5 years of vitamin D supplementation (2,000 IU/day) versus placebo in terms of the primary endpoints of cancer or major cardiovascular disease outcomes.

However, prespecified secondary analyses according to body weight showed that those of normal weight (body mass index < 25.0 kg/m²) did have significant benefits from supplementation versus placebo in terms of cancer incidence (24% lower), cancer mortality (42% lower), and autoimmune disease (22% lower), while no corresponding benefits were observed among those who were overweight or had obesity.

The new analysis adds important context to the trial’s overall findings, noted Katherine N. Bachmann, MD, in an accompanying editorial.

“Thanks to its very large sample size and detailed biomarker analyses, the current study is able to provide novel evidence that responses to vitamin D supplementation may be attenuated in individuals with overweight and obesity, and that this may contribute to the differential outcomes by BMI noted in the original VITAL,” she wrote.

“Further studies are warranted to determine the optimal dose or circulating vitamin D level for individuals with obesity for nonskeletal health-related outcomes,” added Dr. Bachmann, division of diabetes, endocrinology, and metabolism at Vanderbilt University Medical Center, Nashville, Tenn.
 

New analysis examined vitamin D and biomarkers at baseline and 2 years

To take a closer look at the specific changes in vitamin D serum and biomarker levels between the different body-weight groups, Dr. Tobias and colleagues evaluated data from 16,515 participants in the trial (of the 25,000 originally included in VITAL) and looked at changes in key vitamin D serum levels and biomarkers at baseline and follow-up.

Consistent with common observations of lower vitamin D levels with obesity, participants in the higher BMI categories had incrementally lower mean levels of serum total 25-hydroxyvitamin D (25-OHD) prior to randomization, with levels ranging from 32.3 ng/mL for normal weight individuals to 28.0 ng/mL for those with obesity class II (P < .001 for a linear trend).

Baseline levels of other vitamin D biomarkers were also lower with higher BMI, including total 25-OHD 3, free vitamin D (FVD), and bioavailable vitamin D (BioD).

Among 2,742 participants with repeated blood collections at year 2, significant mean increases were observed overall at the end of the study period in serum 25-OHD levels (11.9 ng/mL) among those randomized to vitamin D supplementation, compared with little change in the placebo group (–0.7 ng/mL).

There were also significant increases, overall, in mean total 25-OHD, 25-OHD3, FVD, and BioD levels at 2 years among those receiving supplementation, with little or no change in the placebo group.

When stratified by BMI level, however, the magnitude of increase was lower among those with higher baseline BMI (all treatment effect interactions P < .001). For instance, the mean increases in total 25-OHD level at 2 years for supplementation versus placebo were 13.5 ng/mL for those with a BMI less than 25.0 versus only 10.0 ng/mL for those with a BMI of at least 35.0.

Importantly, even after controlling for baseline vitamin D status of sufficiency or insufficiency, BMI was still significantly associated with changes seen with supplementation.

“It was surprising that, even in the context of low vitamin D levels, those with higher BMI still had a blunted response to supplementation, suggesting the interaction between supplementation and BMI with health outcomes is not simply due to higher prevalence of deficiency,” Dr. Tobias said in an interview. “It really does seem that, even with insufficient or low levels at baseline, those with higher BMI are not able to catch up to sufficient levels as well as those with normal BMI.”
 

Mechanisms?

Among leading theories as to why higher BMI would be associated with lower serum vitamin D levels and a lower response to supplementation is that because vitamin D is a fat-soluble vitamin, the increased adiposity and fat storage capacity with higher BMI results in greater removal of the vitamin from circulation.

“Our results are largely consistent with this hypothesis,” the authors noted.

They added that weight-loss studies, including those involving bariatric surgery, have further shown greater increases in serum 25-OHD or circulating vitamin D levels after weight loss compared with baseline.

Other theories suggest that obesity-induced hepatic dysfunction can contribute to impaired vitamin D metabolism.

Without a clear understanding of the exact mechanisms, the potential for addressing the lower vitamin D levels with, for instance, higher doses of supplementation among those with obesity, also remains unclear, Dr. Tobias noted.

“I think once there’s more clarity on what the mechanism is, then it would make sense to consider what doses could be necessary to achieve the internal levels desired,” she said.

The VITAL study received funding from a grant from the National Center for Complementary and Integrative Health and other sources.

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

A vaccine database found a possible link between the Pfizer/BioNTech bivalent COVID-19 vaccine and ischemic strokes in people over 65 who got the shot, the Centers for Disease Control and Prevention and the Food and Drug Administration said in a joint news release.

The release did not recommend people change their vaccine practices, saying the database finding probably did not represent a “true clinical risk.” The CDC said everybody, including people over 65, should stay up to date on their COVID vaccines, including the bivalent booster.

The news release said the Vaccine Safety Datalink (VSD), “a near real-time surveillance system,” raised a safety concern about the Pfizer/BioNTech booster.

“Rapid-response investigation of the signal in the VSD raised a question of whether people 65 and older who have received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent were more likely to have an ischemic stroke in the 21 days following vaccination compared with days 22-44 following vaccination,” the news release said.

Ischemic strokes are blockages of blood to the brain, often caused by blood clots.

“Although the totality of the data currently suggests that it is very unlikely that the signal in VSD (Vaccine Safety Datalink) represents a true clinical risk, we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal,” the release said.

No higher likelihood of strokes linked to the Pfizer bivalent vaccine had been found by Pfizer/BioNTech, the Department of Veterans Affairs, the Vaccine Adverse Event Reporting System maintained by the CDC and the FDA, or other agencies that monitor reactions of vaccines, the news release said. No safety issues about strokes have been identified with the Moderna bivalent vaccine. 

CNN, citing a CDC official, reported that about 550,000 seniors who got Pfizer bivalent boosters were tracked by the VSD, and 130 of them had strokes within 3 weeks of getting the shot. None of those 130 people died, CNN said. The official spoke on the condition of anonymity because they weren’t authorized to share the data. 

The issue will be discussed at the January meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

In a joint statement, Pfizer and BioNTech said: “Neither Pfizer and BioNTech nor the CDC or FDA have observed similar findings across numerous other monitoring systems in the U.S. and globally and there is no evidence to conclude that ischemic stroke is associated with the use of the companies’ COVID-19 vaccines.”

Bivalent boosters contain two strains of vaccine – one to protect against the original COVID-19 virus and another targeting Omicron subvariants.

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

A vaccine database found a possible link between the Pfizer/BioNTech bivalent COVID-19 vaccine and ischemic strokes in people over 65 who got the shot, the Centers for Disease Control and Prevention and the Food and Drug Administration said in a joint news release.

The release did not recommend people change their vaccine practices, saying the database finding probably did not represent a “true clinical risk.” The CDC said everybody, including people over 65, should stay up to date on their COVID vaccines, including the bivalent booster.

The news release said the Vaccine Safety Datalink (VSD), “a near real-time surveillance system,” raised a safety concern about the Pfizer/BioNTech booster.

“Rapid-response investigation of the signal in the VSD raised a question of whether people 65 and older who have received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent were more likely to have an ischemic stroke in the 21 days following vaccination compared with days 22-44 following vaccination,” the news release said.

Ischemic strokes are blockages of blood to the brain, often caused by blood clots.

“Although the totality of the data currently suggests that it is very unlikely that the signal in VSD (Vaccine Safety Datalink) represents a true clinical risk, we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal,” the release said.

No higher likelihood of strokes linked to the Pfizer bivalent vaccine had been found by Pfizer/BioNTech, the Department of Veterans Affairs, the Vaccine Adverse Event Reporting System maintained by the CDC and the FDA, or other agencies that monitor reactions of vaccines, the news release said. No safety issues about strokes have been identified with the Moderna bivalent vaccine. 

CNN, citing a CDC official, reported that about 550,000 seniors who got Pfizer bivalent boosters were tracked by the VSD, and 130 of them had strokes within 3 weeks of getting the shot. None of those 130 people died, CNN said. The official spoke on the condition of anonymity because they weren’t authorized to share the data. 

The issue will be discussed at the January meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

In a joint statement, Pfizer and BioNTech said: “Neither Pfizer and BioNTech nor the CDC or FDA have observed similar findings across numerous other monitoring systems in the U.S. and globally and there is no evidence to conclude that ischemic stroke is associated with the use of the companies’ COVID-19 vaccines.”

Bivalent boosters contain two strains of vaccine – one to protect against the original COVID-19 virus and another targeting Omicron subvariants.

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

A vaccine database found a possible link between the Pfizer/BioNTech bivalent COVID-19 vaccine and ischemic strokes in people over 65 who got the shot, the Centers for Disease Control and Prevention and the Food and Drug Administration said in a joint news release.

The release did not recommend people change their vaccine practices, saying the database finding probably did not represent a “true clinical risk.” The CDC said everybody, including people over 65, should stay up to date on their COVID vaccines, including the bivalent booster.

The news release said the Vaccine Safety Datalink (VSD), “a near real-time surveillance system,” raised a safety concern about the Pfizer/BioNTech booster.

“Rapid-response investigation of the signal in the VSD raised a question of whether people 65 and older who have received the Pfizer-BioNTech COVID-19 Vaccine, Bivalent were more likely to have an ischemic stroke in the 21 days following vaccination compared with days 22-44 following vaccination,” the news release said.

Ischemic strokes are blockages of blood to the brain, often caused by blood clots.

“Although the totality of the data currently suggests that it is very unlikely that the signal in VSD (Vaccine Safety Datalink) represents a true clinical risk, we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal,” the release said.

No higher likelihood of strokes linked to the Pfizer bivalent vaccine had been found by Pfizer/BioNTech, the Department of Veterans Affairs, the Vaccine Adverse Event Reporting System maintained by the CDC and the FDA, or other agencies that monitor reactions of vaccines, the news release said. No safety issues about strokes have been identified with the Moderna bivalent vaccine. 

CNN, citing a CDC official, reported that about 550,000 seniors who got Pfizer bivalent boosters were tracked by the VSD, and 130 of them had strokes within 3 weeks of getting the shot. None of those 130 people died, CNN said. The official spoke on the condition of anonymity because they weren’t authorized to share the data. 

The issue will be discussed at the January meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

In a joint statement, Pfizer and BioNTech said: “Neither Pfizer and BioNTech nor the CDC or FDA have observed similar findings across numerous other monitoring systems in the U.S. and globally and there is no evidence to conclude that ischemic stroke is associated with the use of the companies’ COVID-19 vaccines.”

Bivalent boosters contain two strains of vaccine – one to protect against the original COVID-19 virus and another targeting Omicron subvariants.

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