Cardiology News

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Fish oil supplementation does not help prevent depression or boost mood, new research suggests.

The VITAL-DEP study included more than 18,000 participants. Among adults aged 50 years or older free of clinically relevant depressive symptoms at baseline, long-term use of marine omega-3 fatty acid (omega-3) supplements did not reduce risk for depression or clinically relevant depressive symptoms — or make a difference in the quality of mood.

In fact, there was a small increase found in risk for depression or depressive symptoms with omega-3 supplements.

“While a small increase in risk of depression was inside the statistical margin of significance, there was no harmful or beneficial effect of omega-3 on the overall course of mood during the roughly 5 to 7 years of follow-up,” lead author Olivia I. Okereke, MD, Massachusetts General Hospital and Harvard Medical School, Boston, told Medscape Medical News.

“The takeaway from our study is that there is no net benefit of long-term use of daily omega-3 fish oil supplements for preventing depression or boosting mood,” Okereke said.

The findings were published online Dec. 21 in JAMA.
 

Assessing general population risk

For many years, experts have recommended omega-3 supplements for reduction in depression recurrence in some high-risk patients, Okereke noted.

“However, there are no guidelines related to the use of omega-3 supplements for preventing depression in the general population. Therefore, we undertook this study to provide clarity in the issue,” she said.

The VITAL-DEP study enrolled 18,353 older adults (mean age, 67.5 years; 49% women). Of these, 16,657 were at risk for incident depression, defined as having no previous history of depression; and 1696 were at risk for recurrent depression, defined as having a history of depression but not having undergone treatment for depression within the past 2 years.

Roughly half the participants were randomly assigned to receive marine omega-3 fatty acids (1 g/d of fish oil, including 465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]) and the other half to matching placebo for an average of 5.3 years.

“Because of the large sample size and long follow-up, we were able to test the effects of daily omega-3 fish oil supplements on universal prevention of depression in the adult population,” Okereke said.
 

No significant benefit

Results showed risk for depression or clinically relevant depressive symptoms (total of incident and recurrent cases) was not significantly different between the omega-3 group and the placebo group.

The omega-3 group had 651 depression or clinically relevant depressive symptom events (13.9 per 1000 person-years), and the placebo group had 583 depression or clinically relevant depressive symptom events (12.3 per 1000 person-years). The hazard ratio was 1.13 (95% CI, 1.01 - 1.26; P = .03).

There were also no significant between-group differences in longitudinal mood scores. The mean difference in change in 8-item Patient Health Questionnaire (PHQ-8) score was 0.03 points (95% CI, −0.01 to 0.07; P = .19).

“Patients, physicians, and other clinicians should understand that there are still many reasons for some people, under the guidance of their health care providers, to take omega-3 fish oil supplements,” Okereke noted.

“These supplements increasingly have been found to have benefits for cardiac disease prevention and treatment of inflammatory conditions, in addition to being used for management of existing depressive disorders in some high-risk patients,” she said.

“However, the results of our study indicate there is no reason for adults in the general population to be taking daily omega-3 fish oil supplements solely for the purpose of preventing depression or for maintaining a positive mood,” she added.

Okereke noted, however, that the VITAL-DEP study used 1 g/day of omega-3 fatty acids and there may be a greater benefit from taking higher doses, such as 4 g/day.
 

Cautionary notes

Commenting on the study for Medscape Medical News, Kuan-Pin Su, MD, PhD, chief of the Department of General Psychiatry, China Medical University, Taichung, Taiwan, highlighted some of the limitations cited by the investigators.

First, depression or depressive symptoms were defined using self-rating scales, which are “convenient to screen for depressive disorders, but a high score obtained on a self-rating scale does not necessarily indicate the presence of depressive psychopathology,” said Su, who was not involved with the research.

He also noted that use of 465 mg of EPA and 375 mg of DHA in VITAL-DEP “might be too low” to have an impact.

Finally, Su said it is “very important to also address the potential for type I error, which makes the secondary and subgroup analyses less reliable.”

VITAL-DEP was supported by a grant from the National Institute of Mental Health. Pronova BioPharma donated the fish oil and matching placebo. Okereke reported receiving royalties from Springer Publishing. Su is a founding committee member of the International Society for Nutritional Psychiatry Research, the board director of the International Society for the Study of Fatty Acids, and an associate editor of the journal Brain, Behavior, and Immunity.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

Editors at the BMJ have released an urgent request to Facebook’s Mark Zuckerberg and parent company Meta regarding a recent “fact-check” on the medical trade journal’s article about questionable Pfizer vaccine trial practices.

According to an open letter written by outgoing BMJ editor-in-chief Fiona Godlee, MD, and incoming editor-in-chief Kamran Abbasi, MD, Facebook hired a third-party contractor to evaluate the article’s findings. This resulted in “inaccurate, incompetent, and irresponsible” conclusions that “should be of concern to anyone who values and relies on sources such as the BMJ for reliable medical information.”

The article in question investigated data integrity concerns at Pfizer vaccine clinical trial sites. In September 2020, the letter states, a former employee of the research group involved in Pfizer’s main vaccine trials, Ventavia, reached out to the BMJ and “began providing ... dozens of internal company documents, photos, audio recordings, and emails.” According to the company’s website, Ventavia “played a significant part in [COVID-19 clinical trial] recruitment” and “has received recognition by Pfizer for their contribution to vaccine trials.”

It was previously reported that the whistle-blower is a former regional director who was involved in Pfizer’s vaccine trials in Texas during the fall of 2020. She alleges “the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.”

The images provided to the BMJ “showed needles discarded in a plastic biohazard bag instead of a sharps container box” and another displayed “vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants.”

Despite informing Ventavia, the director’s concerns went unaddressed. She then filed a complaint with the Food and Drug Administration and was subsequently fired the same day. The FDA did not investigate the director’s allegations, said Dr. Godlee and Dr. Abbasi, even though the evidence “revealed a host of poor clinical trial research practices occurring at Ventavia that could impact data integrity and patient safety.”
 

Article labeled as ‘hoax,’ without pointing out errors

The BMJ hired an investigative reporter to follow up on the clinical trial claims. The findings were published in an article on Nov. 2, 2021, after the article “went through ... the usual high-level legal and editorial oversight and peer review,” according to the journal.

However, by Nov. 10, the journal began receiving complaints from readers unable to share the article on social media. Others had their posts flagged with warnings, such as “missing context ... independent fact-checkers say this information could mislead people.” Administrators of various Facebook groups were notified that posts containing the article were “partly false.”

Readers were informed that Facebook contractor Lead Stories performed the article’s “fact check.” Lead Stories is “an award-winning innovative fact checking and debunking website” and “an active part of Facebook’s partnership with third-party fact checkers” – with the latter granting them “access to listings of content that has been flagged as potentially false by Facebook’s systems or its users.” The company said they “decide independently if we want to fact check it or not.”

Lead Stories stated that they “can enter our fact checks into a tool provided by Facebook and Facebook then uses our data to help slow down the spread of false information on its platform.” Although the contractor is compensated, Lead Stories claims they have “no say or influence over what we fact check or what our conclusions are.”

Both editors question the validity of the fact check performed by Lead Stories, as it failed to provide any “assertions of fact” as to what the BMJ got wrong. Moreover, the editors take issue with Lead Stories referring to the journal as a “news blog” and using the phrase “hoax-alert” in the URL when publishing the story on its site.

The BMJ has reached out to Lead Stories and Facebook, said the letter, but Lead Stories refuses to “change anything about their article or actions that have led to Facebook flagging our article.” Requests for Facebook to remove the “fact-checking” label and allow “readers to freely share the article on [Facebook’s] platform” have been unfruitful.

Dr. Godlee and Dr. Abbasi expressed concern that other “high quality information provider[s] have been affected by the incompetence of Meta’s fact checking regime.” In November, Instagram censored Cochrane, an international provider of independent systematic medical reviews. Instagram, also owned by Meta, prohibited users from tagging Cochrane because the organization “repeatedly posted ... false content about COVID-19 or vaccines.” Cochrane refuted the allegations.

While “fact checking has been a staple of good journalism for decades,” said the editors, Meta has “apparently delegated responsibility to people incompetent in carrying out this crucial task.” They urged the company to reconsider its fact-checking strategy and review the issues that contributed to the error.

This news organization reached out to Meta for comment but did not receive a response at press time.

Lead Stories has posted a reply (Lead Stories’ Response To BMJ Open Letter Objecting To A Lead Stories Fact Check) to the BMJ’s complaint on its website.

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

The amount of fat surrounding abdominal organs may help clinicians identify cardiovascular risk in young people with obesity, researchers have found.

Severely overweight children and young adults showed a subtle association between visceral fat and arterial stiffness independent of body mass index (BMI). The association was not present in those of healthy weight, possibly because their visceral fat stores are too small to have a detectable effect on cardiovascular health, according to the researchers, who reported their findings in the latest issue of Pediatric Obesity.

“Those kids with greater visceral fat had stiffer arteries, which can overtax and overstress the system and lead to unfortunate consequences in terms of cardiovascular health down the line,” senior author Joseph M. Kindler, PhD, an assistant professor of nutritional sciences at the University of Georgia, Athens, told this news organization.

The data came from cross-sectional measurements in 605 youth (67% female, 56% non-Black) aged 10-23 years at Cincinnati Children’s Hospital Medical Center. The sample included 236 individuals of healthy weight, 224 with obesity, and 145 with type 2 diabetes.    

Visceral fat was assessed with dual-energy x-ray absorptiometry (DXA), a widely used test of bone mineral density screening to assess fracture risk. Carotid-femoral pulse wave velocity (PWV) was used to gauge arterial stiffness, a subclinical sign of cardiovascular disease.

Visceral fat was associated with PWV in all three groups of study subjects (P < .05), the researchers found, whereas the amount of subcutaneous fat was linked to arterial stiffness in obese youth and those with obesity but not those whose weight was considered healthy.

The amount of fat was associated with an additional 1.6% of the variability in arterial stiffness in youth with obesity after accounting for BMI. Subcutaneous fat, meanwhile, did not appear to affect PWV, the researchers found. “In youth with healthy weight, visceral fat, subcutaneous fat, BMI, and waist circumference were not significantly associated with PWV in any analyses,” they write.

The researchers cited a paucity of data on the relationship between visceral fat and cardiovascular disease in children with obesity. Although BMI is a reliable and readily available indicator of risk for disease, DXA “might give us a little more information,” Dr. Kindler, a nutritionist and bone biologist, said. As for clinical use to supplement BMI and waist circumference, he said, “maybe there’s room for visceral fat, but we do need a lot more science to back those decisions down the line.”

For example, what normal visceral fat accumulation during childhood looks like is unknown, he said.

Rigorous longitudinal studies are needed to establish cause and effect, but the new findings offer “a potential connection between visceral fat and cardiovascular disease risk in youth in a relatively large sample,” Wei Shen, MD, MPH, the associate director of the body composition unit at the New York Obesity Nutrition Research Center at Columbia University, New York, said.

Ideally, said Dr. Shen, who was not involved in the latest study, it would be “more credible to use the most accurate measure of visceral fat, the volumetric measurement of visceral fat using MRI” to establish a causal relationship with cardiovascular risk. However, MRI is more expensive and less accessible than DXA. To assess visceral fat in the clinic, “waist circumference may still be a good choice, as it is so convenient to use,” she added.

Dr. Kindler and his colleagues highlighted the need to examine the effect of excess visceral fat as well as intrahepatic fat on youth with type 2 diabetes, who experience cardiovascular complications independent of whether they are obese. In the new study, the positive association between visceral fat and arterial stiffness did not differ between youth with obesity and normal glucose control and those with obesity and type 2 diabetes.

Funding came from the Endocrine Fellows Foundation, the National Institutes of Health, and the University of Georgia Obesity Initiative. Dr. Kindler and Dr. Shen have disclosed no relevant financial relationships.

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

The amount of fat surrounding abdominal organs may help clinicians identify cardiovascular risk in young people with obesity, researchers have found.

Severely overweight children and young adults showed a subtle association between visceral fat and arterial stiffness independent of body mass index (BMI). The association was not present in those of healthy weight, possibly because their visceral fat stores are too small to have a detectable effect on cardiovascular health, according to the researchers, who reported their findings in the latest issue of Pediatric Obesity.

“Those kids with greater visceral fat had stiffer arteries, which can overtax and overstress the system and lead to unfortunate consequences in terms of cardiovascular health down the line,” senior author Joseph M. Kindler, PhD, an assistant professor of nutritional sciences at the University of Georgia, Athens, told this news organization.

The data came from cross-sectional measurements in 605 youth (67% female, 56% non-Black) aged 10-23 years at Cincinnati Children’s Hospital Medical Center. The sample included 236 individuals of healthy weight, 224 with obesity, and 145 with type 2 diabetes.    

Visceral fat was assessed with dual-energy x-ray absorptiometry (DXA), a widely used test of bone mineral density screening to assess fracture risk. Carotid-femoral pulse wave velocity (PWV) was used to gauge arterial stiffness, a subclinical sign of cardiovascular disease.

Visceral fat was associated with PWV in all three groups of study subjects (P < .05), the researchers found, whereas the amount of subcutaneous fat was linked to arterial stiffness in obese youth and those with obesity but not those whose weight was considered healthy.

The amount of fat was associated with an additional 1.6% of the variability in arterial stiffness in youth with obesity after accounting for BMI. Subcutaneous fat, meanwhile, did not appear to affect PWV, the researchers found. “In youth with healthy weight, visceral fat, subcutaneous fat, BMI, and waist circumference were not significantly associated with PWV in any analyses,” they write.

The researchers cited a paucity of data on the relationship between visceral fat and cardiovascular disease in children with obesity. Although BMI is a reliable and readily available indicator of risk for disease, DXA “might give us a little more information,” Dr. Kindler, a nutritionist and bone biologist, said. As for clinical use to supplement BMI and waist circumference, he said, “maybe there’s room for visceral fat, but we do need a lot more science to back those decisions down the line.”

For example, what normal visceral fat accumulation during childhood looks like is unknown, he said.

Rigorous longitudinal studies are needed to establish cause and effect, but the new findings offer “a potential connection between visceral fat and cardiovascular disease risk in youth in a relatively large sample,” Wei Shen, MD, MPH, the associate director of the body composition unit at the New York Obesity Nutrition Research Center at Columbia University, New York, said.

Ideally, said Dr. Shen, who was not involved in the latest study, it would be “more credible to use the most accurate measure of visceral fat, the volumetric measurement of visceral fat using MRI” to establish a causal relationship with cardiovascular risk. However, MRI is more expensive and less accessible than DXA. To assess visceral fat in the clinic, “waist circumference may still be a good choice, as it is so convenient to use,” she added.

Dr. Kindler and his colleagues highlighted the need to examine the effect of excess visceral fat as well as intrahepatic fat on youth with type 2 diabetes, who experience cardiovascular complications independent of whether they are obese. In the new study, the positive association between visceral fat and arterial stiffness did not differ between youth with obesity and normal glucose control and those with obesity and type 2 diabetes.

Funding came from the Endocrine Fellows Foundation, the National Institutes of Health, and the University of Georgia Obesity Initiative. Dr. Kindler and Dr. Shen have disclosed no relevant financial relationships.

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

The amount of fat surrounding abdominal organs may help clinicians identify cardiovascular risk in young people with obesity, researchers have found.

Severely overweight children and young adults showed a subtle association between visceral fat and arterial stiffness independent of body mass index (BMI). The association was not present in those of healthy weight, possibly because their visceral fat stores are too small to have a detectable effect on cardiovascular health, according to the researchers, who reported their findings in the latest issue of Pediatric Obesity.

“Those kids with greater visceral fat had stiffer arteries, which can overtax and overstress the system and lead to unfortunate consequences in terms of cardiovascular health down the line,” senior author Joseph M. Kindler, PhD, an assistant professor of nutritional sciences at the University of Georgia, Athens, told this news organization.

The data came from cross-sectional measurements in 605 youth (67% female, 56% non-Black) aged 10-23 years at Cincinnati Children’s Hospital Medical Center. The sample included 236 individuals of healthy weight, 224 with obesity, and 145 with type 2 diabetes.    

Visceral fat was assessed with dual-energy x-ray absorptiometry (DXA), a widely used test of bone mineral density screening to assess fracture risk. Carotid-femoral pulse wave velocity (PWV) was used to gauge arterial stiffness, a subclinical sign of cardiovascular disease.

Visceral fat was associated with PWV in all three groups of study subjects (P < .05), the researchers found, whereas the amount of subcutaneous fat was linked to arterial stiffness in obese youth and those with obesity but not those whose weight was considered healthy.

The amount of fat was associated with an additional 1.6% of the variability in arterial stiffness in youth with obesity after accounting for BMI. Subcutaneous fat, meanwhile, did not appear to affect PWV, the researchers found. “In youth with healthy weight, visceral fat, subcutaneous fat, BMI, and waist circumference were not significantly associated with PWV in any analyses,” they write.

The researchers cited a paucity of data on the relationship between visceral fat and cardiovascular disease in children with obesity. Although BMI is a reliable and readily available indicator of risk for disease, DXA “might give us a little more information,” Dr. Kindler, a nutritionist and bone biologist, said. As for clinical use to supplement BMI and waist circumference, he said, “maybe there’s room for visceral fat, but we do need a lot more science to back those decisions down the line.”

For example, what normal visceral fat accumulation during childhood looks like is unknown, he said.

Rigorous longitudinal studies are needed to establish cause and effect, but the new findings offer “a potential connection between visceral fat and cardiovascular disease risk in youth in a relatively large sample,” Wei Shen, MD, MPH, the associate director of the body composition unit at the New York Obesity Nutrition Research Center at Columbia University, New York, said.

Ideally, said Dr. Shen, who was not involved in the latest study, it would be “more credible to use the most accurate measure of visceral fat, the volumetric measurement of visceral fat using MRI” to establish a causal relationship with cardiovascular risk. However, MRI is more expensive and less accessible than DXA. To assess visceral fat in the clinic, “waist circumference may still be a good choice, as it is so convenient to use,” she added.

Dr. Kindler and his colleagues highlighted the need to examine the effect of excess visceral fat as well as intrahepatic fat on youth with type 2 diabetes, who experience cardiovascular complications independent of whether they are obese. In the new study, the positive association between visceral fat and arterial stiffness did not differ between youth with obesity and normal glucose control and those with obesity and type 2 diabetes.

Funding came from the Endocrine Fellows Foundation, the National Institutes of Health, and the University of Georgia Obesity Initiative. Dr. Kindler and Dr. Shen have disclosed no relevant financial relationships.

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

Patients with obesity and type 2 diabetes who underwent bariatric surgery and had 10-year durable diabetes remission had a 60% lower risk of incident cancer than patients who had usual obesity care.

And women who had bariatric surgery had a 42% lower risk of having cancer during a median 21-year follow-up, compared with women who had usual obesity care.

These findings from 701 patients in the Swedish Obese Subjects (SOS) study who had type 2 diabetes were recently published in Diabetes Care.

The results illustrate the “connection between glucose control and cancer prevention” and suggest that “among patients with type 2 diabetes, many cancer cases are preventable,” lead author Kajsa Sjöholm, PhD, associate professor of molecular medicine at Sahlgrenska Academy, University of Gothenburg (Sweden), said in a press release from the university.

“The global epidemic of both obesity and diabetes leads to an increased risk of cancer, as well as an increased risk of premature death,” added senior author Magdalena Taube, PhD, associate professor of molecular medicine in the same academy.

“It has been estimated that, over the next 10-15 years, obesity may cause more cancer cases than smoking in several countries,” she noted. Therefore, “strategies are needed to prevent this development, and our results can provide vital guidance for prevention of cancer in patients with obesity and type 2 diabetes.”
 

Durable diabetes remission seems key

Two-thirds of the patients in the bariatric surgery group had vertical banded gastroplasty (65%), and the rest had adjustable or nonadjustable gastric banding (18%) or gastric bypass (17%).

Each type of bariatric surgery was associated with higher diabetes remission rates, compared with usual care, in a previous study by these researchers, Dr. Taube said in an interview.

“In our present study,” she added, “we observed a nonsignificant trend, where patients with obesity and type 2 diabetes in the highest weight loss tertile (average weight loss, –44.8 kg) had somewhat lower risk of cancer compared to the lowest tertile [average weight loss, –14.9 kg].”

This might suggest, Dr. Taube continued, that with respect to cancer risk, surgery techniques resulting in greater weight loss (for example, Roux-en-Y gastric bypass and sleeve gastrectomy) should be recommended in patients with obesity and diabetes.

“However, it should also be noted that long-term diabetes remission seems imperative for cancer risk reduction,” she said, “and in a recent meta-analysis by McTigue et al., published in JAMA Surgery, it was shown that patients who had Roux-en-Y gastric bypass had greater weight loss, a slightly higher type 2 diabetes remission rate, less type 2 diabetes relapse, and better long-term glycemic control, compared with those who had sleeve gastrectomy.

“The observed cancer reduction in women with obesity and type 2 diabetes is in line with previous findings showing that cancer risk reduction following bariatric surgery in patients with obesity is more marked among women than men,” Dr. Taube noted. This may be because cancer rates are higher in women with diabetes than in men with diabetes, and common cancer types associated with obesity are female specific.

The main cancers in women were breast cancer, followed by endometrial and colorectal cancer. In men, the main cancers were colorectal, prostate, and urothelial/malignant skin cancer.
 

Study design and findings

It is well established that obesity is a risk factor for 13 types of cancer, and some of these cancers (liver, pancreatic, endometrial, colon and rectal, breast, and bladder) may be related to type 2 diabetes. And bariatric surgery has been shown to reduce cancer risk in patients with obesity.

However, it is not clear how bariatric surgery may affect cancer risk in patients with obesity and type 2 diabetes.

To study this, the researchers examined data from 393 patients who underwent bariatric surgery and 308 patients who received usual obesity treatment, who were part of the SOS study.

The SOS study enrolled men with a body mass index of at least 34 kg/m², and women with a BMI of at least 38 kg/m² who were aged 37-60 years between 1987 and 2001.

The current study outcome – cancer incidence in patients with obesity and type 2 diabetes – was not a prespecified outcome

The intervention groups were matched on 18 variables, including age, sex, serum insulin, alcohol, education, and smoking.

At baseline, the patients had a mean age of about 49 and 60% were women. They had a mean BMI of about 42 and a mean hemoglobin A1c of 7.8%.

On average, patients in the surgery group had lost 27.5 kg and 22.7 kg, and patients in the usual care group had lost 3.2 kg and 4.8 kg, at 2 years and 10 years, respectively.

During a median follow-up of 21 years, there were 74 incident cancers in the control group and 68 cancers in the bariatric surgery group.

The risk of cancer during follow-up was 37% lower in the surgery group than in the usual care group, after multivariable adjustment (adjusted hazard ratio, 0.63; 95% confidence interval, 0.44-0.89; P = .008).

A deeper dive showed that there were 86 incident cancers in women and 56 cancers in men. The risk of cancer was significantly lower in women who had bariatric surgery, compared with those who had usual care (aHR, 0.58; 95% CI 0.38-0.90, P = .016). However, the risk of cancer was not significantly lower in men who had bariatric surgery versus those who had usual care (aHR 0.79, 95% CI, 0.46-1.38; P = .413).

Diabetes remission at 10 years was associated with a 60% reduced cancer incidence (aHR, 0.40; 95% CI, 0.22-0.74, P = .003).

The study was funded by the Swedish state (under an agreement between the Swedish government and the county councils), the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Foundation. One author received consulting fees from Johnson & Johnson. The other authors had no relevant financial disclosures.

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

Patients with obesity and type 2 diabetes who underwent bariatric surgery and had 10-year durable diabetes remission had a 60% lower risk of incident cancer than patients who had usual obesity care.

And women who had bariatric surgery had a 42% lower risk of having cancer during a median 21-year follow-up, compared with women who had usual obesity care.

These findings from 701 patients in the Swedish Obese Subjects (SOS) study who had type 2 diabetes were recently published in Diabetes Care.

The results illustrate the “connection between glucose control and cancer prevention” and suggest that “among patients with type 2 diabetes, many cancer cases are preventable,” lead author Kajsa Sjöholm, PhD, associate professor of molecular medicine at Sahlgrenska Academy, University of Gothenburg (Sweden), said in a press release from the university.

“The global epidemic of both obesity and diabetes leads to an increased risk of cancer, as well as an increased risk of premature death,” added senior author Magdalena Taube, PhD, associate professor of molecular medicine in the same academy.

“It has been estimated that, over the next 10-15 years, obesity may cause more cancer cases than smoking in several countries,” she noted. Therefore, “strategies are needed to prevent this development, and our results can provide vital guidance for prevention of cancer in patients with obesity and type 2 diabetes.”
 

Durable diabetes remission seems key

Two-thirds of the patients in the bariatric surgery group had vertical banded gastroplasty (65%), and the rest had adjustable or nonadjustable gastric banding (18%) or gastric bypass (17%).

Each type of bariatric surgery was associated with higher diabetes remission rates, compared with usual care, in a previous study by these researchers, Dr. Taube said in an interview.

“In our present study,” she added, “we observed a nonsignificant trend, where patients with obesity and type 2 diabetes in the highest weight loss tertile (average weight loss, –44.8 kg) had somewhat lower risk of cancer compared to the lowest tertile [average weight loss, –14.9 kg].”

This might suggest, Dr. Taube continued, that with respect to cancer risk, surgery techniques resulting in greater weight loss (for example, Roux-en-Y gastric bypass and sleeve gastrectomy) should be recommended in patients with obesity and diabetes.

“However, it should also be noted that long-term diabetes remission seems imperative for cancer risk reduction,” she said, “and in a recent meta-analysis by McTigue et al., published in JAMA Surgery, it was shown that patients who had Roux-en-Y gastric bypass had greater weight loss, a slightly higher type 2 diabetes remission rate, less type 2 diabetes relapse, and better long-term glycemic control, compared with those who had sleeve gastrectomy.

“The observed cancer reduction in women with obesity and type 2 diabetes is in line with previous findings showing that cancer risk reduction following bariatric surgery in patients with obesity is more marked among women than men,” Dr. Taube noted. This may be because cancer rates are higher in women with diabetes than in men with diabetes, and common cancer types associated with obesity are female specific.

The main cancers in women were breast cancer, followed by endometrial and colorectal cancer. In men, the main cancers were colorectal, prostate, and urothelial/malignant skin cancer.
 

Study design and findings

It is well established that obesity is a risk factor for 13 types of cancer, and some of these cancers (liver, pancreatic, endometrial, colon and rectal, breast, and bladder) may be related to type 2 diabetes. And bariatric surgery has been shown to reduce cancer risk in patients with obesity.

However, it is not clear how bariatric surgery may affect cancer risk in patients with obesity and type 2 diabetes.

To study this, the researchers examined data from 393 patients who underwent bariatric surgery and 308 patients who received usual obesity treatment, who were part of the SOS study.

The SOS study enrolled men with a body mass index of at least 34 kg/m², and women with a BMI of at least 38 kg/m² who were aged 37-60 years between 1987 and 2001.

The current study outcome – cancer incidence in patients with obesity and type 2 diabetes – was not a prespecified outcome

The intervention groups were matched on 18 variables, including age, sex, serum insulin, alcohol, education, and smoking.

At baseline, the patients had a mean age of about 49 and 60% were women. They had a mean BMI of about 42 and a mean hemoglobin A1c of 7.8%.

On average, patients in the surgery group had lost 27.5 kg and 22.7 kg, and patients in the usual care group had lost 3.2 kg and 4.8 kg, at 2 years and 10 years, respectively.

During a median follow-up of 21 years, there were 74 incident cancers in the control group and 68 cancers in the bariatric surgery group.

The risk of cancer during follow-up was 37% lower in the surgery group than in the usual care group, after multivariable adjustment (adjusted hazard ratio, 0.63; 95% confidence interval, 0.44-0.89; P = .008).

A deeper dive showed that there were 86 incident cancers in women and 56 cancers in men. The risk of cancer was significantly lower in women who had bariatric surgery, compared with those who had usual care (aHR, 0.58; 95% CI 0.38-0.90, P = .016). However, the risk of cancer was not significantly lower in men who had bariatric surgery versus those who had usual care (aHR 0.79, 95% CI, 0.46-1.38; P = .413).

Diabetes remission at 10 years was associated with a 60% reduced cancer incidence (aHR, 0.40; 95% CI, 0.22-0.74, P = .003).

The study was funded by the Swedish state (under an agreement between the Swedish government and the county councils), the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Foundation. One author received consulting fees from Johnson & Johnson. The other authors had no relevant financial disclosures.

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

Patients with obesity and type 2 diabetes who underwent bariatric surgery and had 10-year durable diabetes remission had a 60% lower risk of incident cancer than patients who had usual obesity care.

And women who had bariatric surgery had a 42% lower risk of having cancer during a median 21-year follow-up, compared with women who had usual obesity care.

These findings from 701 patients in the Swedish Obese Subjects (SOS) study who had type 2 diabetes were recently published in Diabetes Care.

The results illustrate the “connection between glucose control and cancer prevention” and suggest that “among patients with type 2 diabetes, many cancer cases are preventable,” lead author Kajsa Sjöholm, PhD, associate professor of molecular medicine at Sahlgrenska Academy, University of Gothenburg (Sweden), said in a press release from the university.

“The global epidemic of both obesity and diabetes leads to an increased risk of cancer, as well as an increased risk of premature death,” added senior author Magdalena Taube, PhD, associate professor of molecular medicine in the same academy.

“It has been estimated that, over the next 10-15 years, obesity may cause more cancer cases than smoking in several countries,” she noted. Therefore, “strategies are needed to prevent this development, and our results can provide vital guidance for prevention of cancer in patients with obesity and type 2 diabetes.”
 

Durable diabetes remission seems key

Two-thirds of the patients in the bariatric surgery group had vertical banded gastroplasty (65%), and the rest had adjustable or nonadjustable gastric banding (18%) or gastric bypass (17%).

Each type of bariatric surgery was associated with higher diabetes remission rates, compared with usual care, in a previous study by these researchers, Dr. Taube said in an interview.

“In our present study,” she added, “we observed a nonsignificant trend, where patients with obesity and type 2 diabetes in the highest weight loss tertile (average weight loss, –44.8 kg) had somewhat lower risk of cancer compared to the lowest tertile [average weight loss, –14.9 kg].”

This might suggest, Dr. Taube continued, that with respect to cancer risk, surgery techniques resulting in greater weight loss (for example, Roux-en-Y gastric bypass and sleeve gastrectomy) should be recommended in patients with obesity and diabetes.

“However, it should also be noted that long-term diabetes remission seems imperative for cancer risk reduction,” she said, “and in a recent meta-analysis by McTigue et al., published in JAMA Surgery, it was shown that patients who had Roux-en-Y gastric bypass had greater weight loss, a slightly higher type 2 diabetes remission rate, less type 2 diabetes relapse, and better long-term glycemic control, compared with those who had sleeve gastrectomy.

“The observed cancer reduction in women with obesity and type 2 diabetes is in line with previous findings showing that cancer risk reduction following bariatric surgery in patients with obesity is more marked among women than men,” Dr. Taube noted. This may be because cancer rates are higher in women with diabetes than in men with diabetes, and common cancer types associated with obesity are female specific.

The main cancers in women were breast cancer, followed by endometrial and colorectal cancer. In men, the main cancers were colorectal, prostate, and urothelial/malignant skin cancer.
 

Study design and findings

It is well established that obesity is a risk factor for 13 types of cancer, and some of these cancers (liver, pancreatic, endometrial, colon and rectal, breast, and bladder) may be related to type 2 diabetes. And bariatric surgery has been shown to reduce cancer risk in patients with obesity.

However, it is not clear how bariatric surgery may affect cancer risk in patients with obesity and type 2 diabetes.

To study this, the researchers examined data from 393 patients who underwent bariatric surgery and 308 patients who received usual obesity treatment, who were part of the SOS study.

The SOS study enrolled men with a body mass index of at least 34 kg/m², and women with a BMI of at least 38 kg/m² who were aged 37-60 years between 1987 and 2001.

The current study outcome – cancer incidence in patients with obesity and type 2 diabetes – was not a prespecified outcome

The intervention groups were matched on 18 variables, including age, sex, serum insulin, alcohol, education, and smoking.

At baseline, the patients had a mean age of about 49 and 60% were women. They had a mean BMI of about 42 and a mean hemoglobin A1c of 7.8%.

On average, patients in the surgery group had lost 27.5 kg and 22.7 kg, and patients in the usual care group had lost 3.2 kg and 4.8 kg, at 2 years and 10 years, respectively.

During a median follow-up of 21 years, there were 74 incident cancers in the control group and 68 cancers in the bariatric surgery group.

The risk of cancer during follow-up was 37% lower in the surgery group than in the usual care group, after multivariable adjustment (adjusted hazard ratio, 0.63; 95% confidence interval, 0.44-0.89; P = .008).

A deeper dive showed that there were 86 incident cancers in women and 56 cancers in men. The risk of cancer was significantly lower in women who had bariatric surgery, compared with those who had usual care (aHR, 0.58; 95% CI 0.38-0.90, P = .016). However, the risk of cancer was not significantly lower in men who had bariatric surgery versus those who had usual care (aHR 0.79, 95% CI, 0.46-1.38; P = .413).

Diabetes remission at 10 years was associated with a 60% reduced cancer incidence (aHR, 0.40; 95% CI, 0.22-0.74, P = .003).

The study was funded by the Swedish state (under an agreement between the Swedish government and the county councils), the Swedish Research Council, the Novo Nordisk Foundation, the Swedish Heart-Lung Foundation, and the Swedish Diabetes Foundation. One author received consulting fees from Johnson & Johnson. The other authors had no relevant financial disclosures.

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

A feasibility study has found that coronary artery calcium scanning has the potential to better target patients who truly need statin therapy, reduce unnecessary statin prescriptions, and improve medication adherence than the current standard of using pooled cohort equations to determine atherosclerotic cardiovascular disease risk.

Researchers at the University of Utah, Salt Lake City, and Intermountain Healthcare, a network of 25 hospitals in Utah, reported that the rate of statin usage in patients evaluated with coronary artery calcium (CAC) was 25% lower than in those whose treatment decisions were based on pooled cohort equations (PCE). None of the patients were on statin therapy when they enrolled in the study, published online in JACC: Cardiovascular Imaging.

“This study demonstrates that doing a large outcomes trial is feasible and has a reasonable likelihood of perhaps being a positive trial for the use of CAC,” lead author Joseph B. Muhlestein, MD, said in an interview. Dr. Muhlestein is codirector of cardiovascular research at Intermountain Healthcare and a professor at the University of Utah.

The findings address the 2018 American College of Cardiology/American Heart Association guideline that states PCE is the “single most robust tool for estimating 10-year risk in U.S. adults 40-75 years of age”. However, the guideline also bases statin determination on shared decision-making between the patient and physician, and recommends CAC for patients for whom a decision about statin treatment is uncertain and those at intermediate risk to fine-tune the need for statins.

The results also have spurred a larger randomized trial known as CorCal, which aims to enroll 5,500 patients and compare CAC and PCE, Dr. Muhlestein said. So far 3,000 patients have been enrolled.
 

Results of CAC vs. PCE

The feasibility study enrolled 601 patients randomized to CAC (302) or PCE (299), 504 of whom were included in the final analysis. In the CAC group, 35.9% went on statin therapy, compared with 47.9% of the PCE patients (P = .005). Participating physicians accepted the study-dictated recommendation to start a statin in 88.1% of patients in the CAC arm versus 75.0% in the PCE arm.

Dr. Muhlestein noted that the feasibility study did not evaluate key outcomes, such as stroke or heart attack, but they will be a key endpoint of the larger randomized trial. “We found in this feasibility study that the recommendations that come from the CAC arm, compared with the PCE arm are significantly different enough that there may be a different outcome,” he said.

“There were cases in which the PCE did not recommend a statin but the patient had a lot of coronary calcium, so we recommended the statin in that patient,” he said. “At the same time, there were also even more patients in which the PCE said they ought to take a statin but they had zero coronary calcium, so we didn’t recommend that they get a statin.”

Compared with PCE-based recommendations, CAC patients were taken off statins in 36% of cases and put on statins in 5.6% of cases. “We think that PCE gives statins to a lot of patients who don’t really need them,” Dr. Muhlestein said.

The feasibility study also found patients were more adherent to therapy if they had CAC than PCE – 63.3% versus 45.6% at a year (P = .03). “Patients and physicians are more likely to be concerned enough to begin preventative therapy when they know that they are not just at risk for the disease, but they actually have the disease; that’s what the CAC score tells them,” Dr. Muhlestein said.

He noted that, while observational evidence has embraced CAC, insurers have been hesitant to cover it. “That is one of the major motivations for us to do this study,” Dr. Muhlestein said. “CAC is not very expensive; it costs less than $100, which is about what it costs to get a lipid panel, but insurance won’t pay for it because we haven’t proved that CAC actually changes outcomes, and that’s a legitimate complaint. But, of course, there’s never been a randomized trial that proves that a PCE changes outcomes either.”

The findings validate the 2018 ACC/AHA guideline “and opens a way to broader use for CAC for statin assessment,” said Neil J. Stone, MD, chair of the ACC/AHA 2013 guideline-writing committee and vice chair of the 2018 committee. “The study confirms a large body of information that a deterministic approach, i.e., calcium score, outperforms a probabilistic approach on an individual patient level.” Dr. Stone is the Bonow Professor of Medicine at Northwestern University and medical director of the Vascular Center of the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital, both in Chicago.

“I applaud the investigators for using this as a hypothesis-generating study and planning a larger, more definitive trial,” he said. “This study would encourage regulators and insurance companies to support the use of calcium scores as recommended by the 2018 guideline.”

Intermountain Healthcare is the sole source of funding for the CorCal feasibility study. Dr. Muhlestein and Dr. Stone have no relevant relationships to disclose.
 

A feasibility study has found that coronary artery calcium scanning has the potential to better target patients who truly need statin therapy, reduce unnecessary statin prescriptions, and improve medication adherence than the current standard of using pooled cohort equations to determine atherosclerotic cardiovascular disease risk.

Researchers at the University of Utah, Salt Lake City, and Intermountain Healthcare, a network of 25 hospitals in Utah, reported that the rate of statin usage in patients evaluated with coronary artery calcium (CAC) was 25% lower than in those whose treatment decisions were based on pooled cohort equations (PCE). None of the patients were on statin therapy when they enrolled in the study, published online in JACC: Cardiovascular Imaging.

“This study demonstrates that doing a large outcomes trial is feasible and has a reasonable likelihood of perhaps being a positive trial for the use of CAC,” lead author Joseph B. Muhlestein, MD, said in an interview. Dr. Muhlestein is codirector of cardiovascular research at Intermountain Healthcare and a professor at the University of Utah.

The findings address the 2018 American College of Cardiology/American Heart Association guideline that states PCE is the “single most robust tool for estimating 10-year risk in U.S. adults 40-75 years of age”. However, the guideline also bases statin determination on shared decision-making between the patient and physician, and recommends CAC for patients for whom a decision about statin treatment is uncertain and those at intermediate risk to fine-tune the need for statins.

The results also have spurred a larger randomized trial known as CorCal, which aims to enroll 5,500 patients and compare CAC and PCE, Dr. Muhlestein said. So far 3,000 patients have been enrolled.
 

Results of CAC vs. PCE

The feasibility study enrolled 601 patients randomized to CAC (302) or PCE (299), 504 of whom were included in the final analysis. In the CAC group, 35.9% went on statin therapy, compared with 47.9% of the PCE patients (P = .005). Participating physicians accepted the study-dictated recommendation to start a statin in 88.1% of patients in the CAC arm versus 75.0% in the PCE arm.

Dr. Muhlestein noted that the feasibility study did not evaluate key outcomes, such as stroke or heart attack, but they will be a key endpoint of the larger randomized trial. “We found in this feasibility study that the recommendations that come from the CAC arm, compared with the PCE arm are significantly different enough that there may be a different outcome,” he said.

“There were cases in which the PCE did not recommend a statin but the patient had a lot of coronary calcium, so we recommended the statin in that patient,” he said. “At the same time, there were also even more patients in which the PCE said they ought to take a statin but they had zero coronary calcium, so we didn’t recommend that they get a statin.”

Compared with PCE-based recommendations, CAC patients were taken off statins in 36% of cases and put on statins in 5.6% of cases. “We think that PCE gives statins to a lot of patients who don’t really need them,” Dr. Muhlestein said.

The feasibility study also found patients were more adherent to therapy if they had CAC than PCE – 63.3% versus 45.6% at a year (P = .03). “Patients and physicians are more likely to be concerned enough to begin preventative therapy when they know that they are not just at risk for the disease, but they actually have the disease; that’s what the CAC score tells them,” Dr. Muhlestein said.

He noted that, while observational evidence has embraced CAC, insurers have been hesitant to cover it. “That is one of the major motivations for us to do this study,” Dr. Muhlestein said. “CAC is not very expensive; it costs less than $100, which is about what it costs to get a lipid panel, but insurance won’t pay for it because we haven’t proved that CAC actually changes outcomes, and that’s a legitimate complaint. But, of course, there’s never been a randomized trial that proves that a PCE changes outcomes either.”

The findings validate the 2018 ACC/AHA guideline “and opens a way to broader use for CAC for statin assessment,” said Neil J. Stone, MD, chair of the ACC/AHA 2013 guideline-writing committee and vice chair of the 2018 committee. “The study confirms a large body of information that a deterministic approach, i.e., calcium score, outperforms a probabilistic approach on an individual patient level.” Dr. Stone is the Bonow Professor of Medicine at Northwestern University and medical director of the Vascular Center of the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital, both in Chicago.

“I applaud the investigators for using this as a hypothesis-generating study and planning a larger, more definitive trial,” he said. “This study would encourage regulators and insurance companies to support the use of calcium scores as recommended by the 2018 guideline.”

Intermountain Healthcare is the sole source of funding for the CorCal feasibility study. Dr. Muhlestein and Dr. Stone have no relevant relationships to disclose.
 

A feasibility study has found that coronary artery calcium scanning has the potential to better target patients who truly need statin therapy, reduce unnecessary statin prescriptions, and improve medication adherence than the current standard of using pooled cohort equations to determine atherosclerotic cardiovascular disease risk.

Researchers at the University of Utah, Salt Lake City, and Intermountain Healthcare, a network of 25 hospitals in Utah, reported that the rate of statin usage in patients evaluated with coronary artery calcium (CAC) was 25% lower than in those whose treatment decisions were based on pooled cohort equations (PCE). None of the patients were on statin therapy when they enrolled in the study, published online in JACC: Cardiovascular Imaging.

“This study demonstrates that doing a large outcomes trial is feasible and has a reasonable likelihood of perhaps being a positive trial for the use of CAC,” lead author Joseph B. Muhlestein, MD, said in an interview. Dr. Muhlestein is codirector of cardiovascular research at Intermountain Healthcare and a professor at the University of Utah.

The findings address the 2018 American College of Cardiology/American Heart Association guideline that states PCE is the “single most robust tool for estimating 10-year risk in U.S. adults 40-75 years of age”. However, the guideline also bases statin determination on shared decision-making between the patient and physician, and recommends CAC for patients for whom a decision about statin treatment is uncertain and those at intermediate risk to fine-tune the need for statins.

The results also have spurred a larger randomized trial known as CorCal, which aims to enroll 5,500 patients and compare CAC and PCE, Dr. Muhlestein said. So far 3,000 patients have been enrolled.
 

Results of CAC vs. PCE

The feasibility study enrolled 601 patients randomized to CAC (302) or PCE (299), 504 of whom were included in the final analysis. In the CAC group, 35.9% went on statin therapy, compared with 47.9% of the PCE patients (P = .005). Participating physicians accepted the study-dictated recommendation to start a statin in 88.1% of patients in the CAC arm versus 75.0% in the PCE arm.

Dr. Muhlestein noted that the feasibility study did not evaluate key outcomes, such as stroke or heart attack, but they will be a key endpoint of the larger randomized trial. “We found in this feasibility study that the recommendations that come from the CAC arm, compared with the PCE arm are significantly different enough that there may be a different outcome,” he said.

“There were cases in which the PCE did not recommend a statin but the patient had a lot of coronary calcium, so we recommended the statin in that patient,” he said. “At the same time, there were also even more patients in which the PCE said they ought to take a statin but they had zero coronary calcium, so we didn’t recommend that they get a statin.”

Compared with PCE-based recommendations, CAC patients were taken off statins in 36% of cases and put on statins in 5.6% of cases. “We think that PCE gives statins to a lot of patients who don’t really need them,” Dr. Muhlestein said.

The feasibility study also found patients were more adherent to therapy if they had CAC than PCE – 63.3% versus 45.6% at a year (P = .03). “Patients and physicians are more likely to be concerned enough to begin preventative therapy when they know that they are not just at risk for the disease, but they actually have the disease; that’s what the CAC score tells them,” Dr. Muhlestein said.

He noted that, while observational evidence has embraced CAC, insurers have been hesitant to cover it. “That is one of the major motivations for us to do this study,” Dr. Muhlestein said. “CAC is not very expensive; it costs less than $100, which is about what it costs to get a lipid panel, but insurance won’t pay for it because we haven’t proved that CAC actually changes outcomes, and that’s a legitimate complaint. But, of course, there’s never been a randomized trial that proves that a PCE changes outcomes either.”

The findings validate the 2018 ACC/AHA guideline “and opens a way to broader use for CAC for statin assessment,” said Neil J. Stone, MD, chair of the ACC/AHA 2013 guideline-writing committee and vice chair of the 2018 committee. “The study confirms a large body of information that a deterministic approach, i.e., calcium score, outperforms a probabilistic approach on an individual patient level.” Dr. Stone is the Bonow Professor of Medicine at Northwestern University and medical director of the Vascular Center of the Bluhm Cardiovascular Institute of Northwestern Memorial Hospital, both in Chicago.

“I applaud the investigators for using this as a hypothesis-generating study and planning a larger, more definitive trial,” he said. “This study would encourage regulators and insurance companies to support the use of calcium scores as recommended by the 2018 guideline.”

Intermountain Healthcare is the sole source of funding for the CorCal feasibility study. Dr. Muhlestein and Dr. Stone have no relevant relationships to disclose.
 

It has been well established that device closure has, on average, prevented stroke recurrence in people who’ve had patent foramen ovale–associated stroke, but a meta-analysis has drilled down into clinical trials to advance a potentially practice-changing principle: that, while device closure shows an overall benefit, not all patients derive a benefit and some may actually be harmed by the procedure.

What’s more, the researchers developed a scoring system that helps determine which patients are likely to benefit from device closure.

“What was unknown was how to treat individual patients because the decision to close the patent foramen ovale (PFO) is still preference sensitive because the risk of a recurrent stroke is low, and most of the strokes that recur are not terribly severe,” lead study author David M. Kent, MD, MS, said in an interview.

“On top of this,” he said, “it was still suspected that some of the PFOs, even in trials of well-selected patients, may not be causally related to stroke; the stroke may still have another occult cause, such as paroxysmal atrial fibrillation or aortic arch atheroma.” Dr. Kent is a professor of medicine at Tufts University in Boston and director of the Predictive Analytics and Comparative Effectiveness Center there.

The meta-analysis, conducted by the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium, analyzed data from six randomized clinical trials that compared device closure and medical therapy to medical therapy alone in 3,740 patients who had PFO-associated stroke from 2000 to 2017. It was published in JAMA.

Overall, the rate of recurrent ischemic stroke was less than half that in patients who had device closure, compared with those who were on medical therapy: 0.47% (n = 39 of 1,889) vs. 1.09% (n = 82 of 1,851).

The researchers also applied two tools designed to calculate the probability of recurrent stroke in individual patients: Risk of Paradoxical Embolism (RoPE), an index that assigns a score of 0-10 to stratify cryptogenic stroke patients with PFO by the likelihood that the stroke was associated with their PFO; and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system, which integrates the RoPE score with physiological and anatomical features – namely, the size of the PFO shunt and the presence of an atrial septal aneurysm.

“We came up with a way to more accurately identify those patients who are likely to get the most benefit from PFO closure based on mathematic modeling that estimates an individual’s probability that the PFO is causally related to the stroke,” Dr. Kent said.
 

Multivariate analysis determines risk

The study used a multivariate classification system that Dr. Kent had been developing to perform subgroup analyses of the clinical trials. It assigned patients to three different risk groups based on the likelihood that the PFO was causally related to their stroke: PASCAL categories of unlikely, possible, and probable.

The PASCAL unlikely group had a risk of stroke recurrence in the first 2 years of 3.4% (95% confidence interval, 1.1%-5.7%) if they were on medical therapy, and 4.1% (95% CI, 1.7%-6.4%) if they had device closure. In the PASCAL possible group, those risks were 3.6% (95% CI, 2.4%-4.9%) and 1.5% (95% CI, 0.7-2.3%), respectively. For the probable group, device closure represents “a near perfect therapy” with a 90% risk reduction, Dr. Kent said. “Moreover,” he said, “adverse events of device closure, such as atrial fibrillation, appear to be concentrated in those patients who fall into the unlikely classification, who appear to get no benefit.”

The ideal patient for device closure is age 60 years or younger and without vascular risk factors such as hypertension, diabetes, a history of smoking, or a prior stroke, but has high-risk PFO features such as a large shunt or atrial septal aneurysm, Dr. Kent said.

“We think these findings should be practice changing now,” Dr. Kent said.

It has been well established that device closure has, on average, prevented stroke recurrence in people who’ve had patent foramen ovale–associated stroke, but a meta-analysis has drilled down into clinical trials to advance a potentially practice-changing principle: that, while device closure shows an overall benefit, not all patients derive a benefit and some may actually be harmed by the procedure.

What’s more, the researchers developed a scoring system that helps determine which patients are likely to benefit from device closure.

“What was unknown was how to treat individual patients because the decision to close the patent foramen ovale (PFO) is still preference sensitive because the risk of a recurrent stroke is low, and most of the strokes that recur are not terribly severe,” lead study author David M. Kent, MD, MS, said in an interview.

“On top of this,” he said, “it was still suspected that some of the PFOs, even in trials of well-selected patients, may not be causally related to stroke; the stroke may still have another occult cause, such as paroxysmal atrial fibrillation or aortic arch atheroma.” Dr. Kent is a professor of medicine at Tufts University in Boston and director of the Predictive Analytics and Comparative Effectiveness Center there.

The meta-analysis, conducted by the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium, analyzed data from six randomized clinical trials that compared device closure and medical therapy to medical therapy alone in 3,740 patients who had PFO-associated stroke from 2000 to 2017. It was published in JAMA.

Overall, the rate of recurrent ischemic stroke was less than half that in patients who had device closure, compared with those who were on medical therapy: 0.47% (n = 39 of 1,889) vs. 1.09% (n = 82 of 1,851).

The researchers also applied two tools designed to calculate the probability of recurrent stroke in individual patients: Risk of Paradoxical Embolism (RoPE), an index that assigns a score of 0-10 to stratify cryptogenic stroke patients with PFO by the likelihood that the stroke was associated with their PFO; and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system, which integrates the RoPE score with physiological and anatomical features – namely, the size of the PFO shunt and the presence of an atrial septal aneurysm.

“We came up with a way to more accurately identify those patients who are likely to get the most benefit from PFO closure based on mathematic modeling that estimates an individual’s probability that the PFO is causally related to the stroke,” Dr. Kent said.
 

Multivariate analysis determines risk

The study used a multivariate classification system that Dr. Kent had been developing to perform subgroup analyses of the clinical trials. It assigned patients to three different risk groups based on the likelihood that the PFO was causally related to their stroke: PASCAL categories of unlikely, possible, and probable.

The PASCAL unlikely group had a risk of stroke recurrence in the first 2 years of 3.4% (95% confidence interval, 1.1%-5.7%) if they were on medical therapy, and 4.1% (95% CI, 1.7%-6.4%) if they had device closure. In the PASCAL possible group, those risks were 3.6% (95% CI, 2.4%-4.9%) and 1.5% (95% CI, 0.7-2.3%), respectively. For the probable group, device closure represents “a near perfect therapy” with a 90% risk reduction, Dr. Kent said. “Moreover,” he said, “adverse events of device closure, such as atrial fibrillation, appear to be concentrated in those patients who fall into the unlikely classification, who appear to get no benefit.”

The ideal patient for device closure is age 60 years or younger and without vascular risk factors such as hypertension, diabetes, a history of smoking, or a prior stroke, but has high-risk PFO features such as a large shunt or atrial septal aneurysm, Dr. Kent said.

“We think these findings should be practice changing now,” Dr. Kent said.

It has been well established that device closure has, on average, prevented stroke recurrence in people who’ve had patent foramen ovale–associated stroke, but a meta-analysis has drilled down into clinical trials to advance a potentially practice-changing principle: that, while device closure shows an overall benefit, not all patients derive a benefit and some may actually be harmed by the procedure.

What’s more, the researchers developed a scoring system that helps determine which patients are likely to benefit from device closure.

“What was unknown was how to treat individual patients because the decision to close the patent foramen ovale (PFO) is still preference sensitive because the risk of a recurrent stroke is low, and most of the strokes that recur are not terribly severe,” lead study author David M. Kent, MD, MS, said in an interview.

“On top of this,” he said, “it was still suspected that some of the PFOs, even in trials of well-selected patients, may not be causally related to stroke; the stroke may still have another occult cause, such as paroxysmal atrial fibrillation or aortic arch atheroma.” Dr. Kent is a professor of medicine at Tufts University in Boston and director of the Predictive Analytics and Comparative Effectiveness Center there.

The meta-analysis, conducted by the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) consortium, analyzed data from six randomized clinical trials that compared device closure and medical therapy to medical therapy alone in 3,740 patients who had PFO-associated stroke from 2000 to 2017. It was published in JAMA.

Overall, the rate of recurrent ischemic stroke was less than half that in patients who had device closure, compared with those who were on medical therapy: 0.47% (n = 39 of 1,889) vs. 1.09% (n = 82 of 1,851).

The researchers also applied two tools designed to calculate the probability of recurrent stroke in individual patients: Risk of Paradoxical Embolism (RoPE), an index that assigns a score of 0-10 to stratify cryptogenic stroke patients with PFO by the likelihood that the stroke was associated with their PFO; and the PFO-Associated Stroke Causal Likelihood (PASCAL) classification system, which integrates the RoPE score with physiological and anatomical features – namely, the size of the PFO shunt and the presence of an atrial septal aneurysm.

“We came up with a way to more accurately identify those patients who are likely to get the most benefit from PFO closure based on mathematic modeling that estimates an individual’s probability that the PFO is causally related to the stroke,” Dr. Kent said.
 

Multivariate analysis determines risk

The study used a multivariate classification system that Dr. Kent had been developing to perform subgroup analyses of the clinical trials. It assigned patients to three different risk groups based on the likelihood that the PFO was causally related to their stroke: PASCAL categories of unlikely, possible, and probable.

The PASCAL unlikely group had a risk of stroke recurrence in the first 2 years of 3.4% (95% confidence interval, 1.1%-5.7%) if they were on medical therapy, and 4.1% (95% CI, 1.7%-6.4%) if they had device closure. In the PASCAL possible group, those risks were 3.6% (95% CI, 2.4%-4.9%) and 1.5% (95% CI, 0.7-2.3%), respectively. For the probable group, device closure represents “a near perfect therapy” with a 90% risk reduction, Dr. Kent said. “Moreover,” he said, “adverse events of device closure, such as atrial fibrillation, appear to be concentrated in those patients who fall into the unlikely classification, who appear to get no benefit.”

The ideal patient for device closure is age 60 years or younger and without vascular risk factors such as hypertension, diabetes, a history of smoking, or a prior stroke, but has high-risk PFO features such as a large shunt or atrial septal aneurysm, Dr. Kent said.

“We think these findings should be practice changing now,” Dr. Kent said.

Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.

The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.

The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.

“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.    

“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.

“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.

To date, there have been seven complaints and no injuries or deaths reported for this device.

The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website. 

Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.

Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].

Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.

Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.

The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.

The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.

“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.    

“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.

“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.

To date, there have been seven complaints and no injuries or deaths reported for this device.

The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website. 

Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.

Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].

Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.

Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Arrow International, a subsidiary of Teleflex, has recalled a total of 3,241 Arrow-Trerotola over-the-wire 7FR percutaneous thrombolytic device (PTD) kits because of the risk of the orange inner lumen of the catheter’s tip component separating from the basket.

The U.S. Food and Drug Administration has identified this as a Class I recall, the most serious type, because of the potential for serious injury or death.

The recalled kits include a rotatable catheter with an outer sheath and an inner cable with a self-expanding basket. The Arrow-Trerotola PTD catheter is used with the Arrow rotator drive unit to remove clots in patients with arteriovenous fistulas and synthetic dialysis grafts.

“If the orange inner lumen separates from the basket, it may fracture and detach and block the blood vessel(s),” the FDA says in the recall notice posted on the FDA website.    

“If the orange inner lumen detaches from the basket, health consequences depend upon where the fractured tip component embolizes. If the embolization is local to the treatment target site, retrieval may be attempted, requiring an additional intervention and consequent delay of therapy,” the agency notes.

“In some cases, the embolization could be central or possibly even to the heart or pulmonary arteries. This may lead to serious adverse events such as vessel damage, need for additional medical procedures, or possibly death,” the agency says.

To date, there have been seven complaints and no injuries or deaths reported for this device.

The recalled devices were distributed in the United States between Nov. 1, 2019, and July 31, 2021. Product codes and lot numbers pertaining to the devices are listed on the FDA website. 

Teleflex has sent an urgent field safety notice to customers requesting that they check inventory for affected product and remove and quarantine all recalled product.

Customers are also asked to complete the enclosed acknowledgement form and fax it to 1-855-419-8507 (attention: customer service) or e-mail the form to [email protected].

Customers with recalled product service will be contacted by a company representative with instructions for returning any recalled products.

Customers who have questions about this recall should contact Teleflex customer service by phone at 1-866-396-2111, by fax at 1-855-419-8507, or by email at [email protected].

Health care providers can report adverse reactions or quality problems they experience using these devices to the FDA’s MedWatch program.

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

Top infectious disease officials expect a surge of COVID-19 cases after the holidays and say Omicron will soon take over as the dominant strain in the United States.

The best way to stay protected is by getting vaccinated and boosted, they said.

“For the unvaccinated, you’re looking at a winter of severe illness and death – for yourselves, families, and the hospitals who may soon overwhelm,” White House COVID-19 Response Coordinator Jeff Zients said at a news briefing Dec. 17. “We need the American people to do their part.”

The Omicron variant has been detected in at least 39 states and 75 countries, according to CDC director Rochelle Walensky, MD.

The strain is more transmissible than the already highly infectious Delta variant, and although there was early evidence that it caused more mild disease, she said that is likely because many of those infected have been vaccinated and boosted.

“Although Delta continues to circulate widely in the United States, Omicron is increasing rapidly and we expect it to become the dominant strain in the United States, as it has in other countries, in the coming weeks,” Dr. Walensky said.

The United States is averaging close to 1,300 deaths from COVID-19 each day. New cases, deaths, and hospitalizations are higher now than in the previous winter – before vaccines were so widely available. The New York Times reported on Dec. 17 that new infections in Connecticut and Maine have grown 150% in the past 2 weeks, and Ohio and Indiana are seeing hospitalization rates nearing the worst of 2020-2021’s winter surge.

Dueling reports released recently gave cause for relief and concern about Omicron.

A study from South Africa released on Dec. 14 shows lower hospitalizations during the first 3 weeks of the Omicron wave than during earlier waves from other variants. That’s the good news.

The concerning news is out of the United Kingdom, where Imperial College London reported Dec. 17 that the risk of reinfection with COVID-19 from Omicron is more than 5 times as high and that cases of Omicron-based COVID-19 are doubling every 2 days.

What’s more, the study “finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection. However, hospitalization data remains very limited at this time,” the researchers said.

“We have no evidence that the virus itself is more mild,” Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape, told PBS NewsHour. “Until we have that, we have to assume that people who don’t have any protection are highly vulnerable to getting very ill.”

The White House COVID-19 team continues to urge parents and guardians to get their children vaccinated, especially in anticipation of a post-holiday spike. Dr. Walensky said the CDC’s vaccine advisory board met on Dec. 16 to continue the safety discussion about COVID-19 vaccinations in children.

So far, 20 million children under 17 and 5 million under 11 have received their shots.

“Looking specifically at vaccine safety data from over 50,000 children 5-11 years old, we found no evidence of serious safety concerns,” Dr. Walensky said.

Top infectious disease expert Anthony S. Fauci, MD, highlighted the importance of getting vaccinated and boosted to avoid serious disease from Delta and Omicron.

“We’re in a situation where we are now facing a very important Delta surge and we are looking over our shoulder at an oncoming Omicron surge,” he said. “The optimum protection is fully vaccinated plus a boost.”

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

Top infectious disease officials expect a surge of COVID-19 cases after the holidays and say Omicron will soon take over as the dominant strain in the United States.

The best way to stay protected is by getting vaccinated and boosted, they said.

“For the unvaccinated, you’re looking at a winter of severe illness and death – for yourselves, families, and the hospitals who may soon overwhelm,” White House COVID-19 Response Coordinator Jeff Zients said at a news briefing Dec. 17. “We need the American people to do their part.”

The Omicron variant has been detected in at least 39 states and 75 countries, according to CDC director Rochelle Walensky, MD.

The strain is more transmissible than the already highly infectious Delta variant, and although there was early evidence that it caused more mild disease, she said that is likely because many of those infected have been vaccinated and boosted.

“Although Delta continues to circulate widely in the United States, Omicron is increasing rapidly and we expect it to become the dominant strain in the United States, as it has in other countries, in the coming weeks,” Dr. Walensky said.

The United States is averaging close to 1,300 deaths from COVID-19 each day. New cases, deaths, and hospitalizations are higher now than in the previous winter – before vaccines were so widely available. The New York Times reported on Dec. 17 that new infections in Connecticut and Maine have grown 150% in the past 2 weeks, and Ohio and Indiana are seeing hospitalization rates nearing the worst of 2020-2021’s winter surge.

Dueling reports released recently gave cause for relief and concern about Omicron.

A study from South Africa released on Dec. 14 shows lower hospitalizations during the first 3 weeks of the Omicron wave than during earlier waves from other variants. That’s the good news.

The concerning news is out of the United Kingdom, where Imperial College London reported Dec. 17 that the risk of reinfection with COVID-19 from Omicron is more than 5 times as high and that cases of Omicron-based COVID-19 are doubling every 2 days.

What’s more, the study “finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection. However, hospitalization data remains very limited at this time,” the researchers said.

“We have no evidence that the virus itself is more mild,” Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape, told PBS NewsHour. “Until we have that, we have to assume that people who don’t have any protection are highly vulnerable to getting very ill.”

The White House COVID-19 team continues to urge parents and guardians to get their children vaccinated, especially in anticipation of a post-holiday spike. Dr. Walensky said the CDC’s vaccine advisory board met on Dec. 16 to continue the safety discussion about COVID-19 vaccinations in children.

So far, 20 million children under 17 and 5 million under 11 have received their shots.

“Looking specifically at vaccine safety data from over 50,000 children 5-11 years old, we found no evidence of serious safety concerns,” Dr. Walensky said.

Top infectious disease expert Anthony S. Fauci, MD, highlighted the importance of getting vaccinated and boosted to avoid serious disease from Delta and Omicron.

“We’re in a situation where we are now facing a very important Delta surge and we are looking over our shoulder at an oncoming Omicron surge,” he said. “The optimum protection is fully vaccinated plus a boost.”

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

Top infectious disease officials expect a surge of COVID-19 cases after the holidays and say Omicron will soon take over as the dominant strain in the United States.

The best way to stay protected is by getting vaccinated and boosted, they said.

“For the unvaccinated, you’re looking at a winter of severe illness and death – for yourselves, families, and the hospitals who may soon overwhelm,” White House COVID-19 Response Coordinator Jeff Zients said at a news briefing Dec. 17. “We need the American people to do their part.”

The Omicron variant has been detected in at least 39 states and 75 countries, according to CDC director Rochelle Walensky, MD.

The strain is more transmissible than the already highly infectious Delta variant, and although there was early evidence that it caused more mild disease, she said that is likely because many of those infected have been vaccinated and boosted.

“Although Delta continues to circulate widely in the United States, Omicron is increasing rapidly and we expect it to become the dominant strain in the United States, as it has in other countries, in the coming weeks,” Dr. Walensky said.

The United States is averaging close to 1,300 deaths from COVID-19 each day. New cases, deaths, and hospitalizations are higher now than in the previous winter – before vaccines were so widely available. The New York Times reported on Dec. 17 that new infections in Connecticut and Maine have grown 150% in the past 2 weeks, and Ohio and Indiana are seeing hospitalization rates nearing the worst of 2020-2021’s winter surge.

Dueling reports released recently gave cause for relief and concern about Omicron.

A study from South Africa released on Dec. 14 shows lower hospitalizations during the first 3 weeks of the Omicron wave than during earlier waves from other variants. That’s the good news.

The concerning news is out of the United Kingdom, where Imperial College London reported Dec. 17 that the risk of reinfection with COVID-19 from Omicron is more than 5 times as high and that cases of Omicron-based COVID-19 are doubling every 2 days.

What’s more, the study “finds no evidence of Omicron having lower severity than Delta, judged by either the proportion of people testing positive who report symptoms, or by the proportion of cases seeking hospital care after infection. However, hospitalization data remains very limited at this time,” the researchers said.

“We have no evidence that the virus itself is more mild,” Eric Topol, MD, executive vice president of Scripps Research and editor-in-chief of Medscape, told PBS NewsHour. “Until we have that, we have to assume that people who don’t have any protection are highly vulnerable to getting very ill.”

The White House COVID-19 team continues to urge parents and guardians to get their children vaccinated, especially in anticipation of a post-holiday spike. Dr. Walensky said the CDC’s vaccine advisory board met on Dec. 16 to continue the safety discussion about COVID-19 vaccinations in children.

So far, 20 million children under 17 and 5 million under 11 have received their shots.

“Looking specifically at vaccine safety data from over 50,000 children 5-11 years old, we found no evidence of serious safety concerns,” Dr. Walensky said.

Top infectious disease expert Anthony S. Fauci, MD, highlighted the importance of getting vaccinated and boosted to avoid serious disease from Delta and Omicron.

“We’re in a situation where we are now facing a very important Delta surge and we are looking over our shoulder at an oncoming Omicron surge,” he said. “The optimum protection is fully vaccinated plus a boost.”

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

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

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

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

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

The first large population study to investigate the association between different COVID-19 vaccines types and cardiac effects and adverse events shows a small increase in the risk for acute myocarditis with both the mRNA-based vaccines and – in what may a first in the literature – an adenovirus-vector vaccine.

Ivan Pantic/Getty Images

The excess risk was seen following the first dose of the ChAdOc1 (AstraZeneca/Oxford), the adenovirus-based vaccine, and the mRNA-based BNT162b2 (Pfizer/BioNTech). It was observed after first and second doses of the mRNA-1273 (Moderna) vaccine.

The incidence rate ratios for myocarditis 1-7 days after the first AstraZeneca, Pfizer, and Moderna injections were 1.76, 1.45, and 8.38, respectively, and 23.1 after the second dose of the Moderna vaccine.

“There’s a bit more uncertainty and worry about mRNA vaccines because it’s quite a new vector for vaccination and, therefore, there’s been more focus on the potential side effects,” said Nicholas Mills, MD.

“But it doesn’t surprise me the signal is present for all types of vaccines because they’re designed to generate a systemic immune response and that is, unfortunately, where you can cause small risks for immune-mediated illnesses like myocarditis,” Dr. Mills, from the University of Edinburgh, told this news organization. Dr. Mills is a coauthor on the study, published Dec. 14 in Nature Medicine.

To put the risks in context, the group estimated between 1 and 10 additional myocarditis hospitalizations or deaths per 1 million people vaccinated, but 40 excess myocarditis events per million following a positive SARS-CoV-2 test result.

As reported, rates of excess myocarditis events associated with a first dose were 2 per million injections of the AstraZeneca vaccine, 1 per million for the Pfizer vaccine, and 6 per million with the Moderna vaccine.

Following a second dose, there were 10 additional myocarditis events per million people receiving the Moderna vaccine and none among recipients of the AstraZeneca or Pfizer vaccines.

“It was particularly seen within the first 7 days of the first dose, which is very consistent with what we see in people who have viral myocarditis,” Dr. Mills said. “So it looks like a real signal but it’s very small.”

The results are in line with previous studies of the Pfizer vaccine in Israel and studies of the Moderna vaccine in the United States, Biykem Bozkurt, MD, PhD, professor of medicine at Baylor College of Medicine, Houston, told this news organization.

“What this paper does is confirm that cardiovascular complications – and they are only looking at a small component of those cardiovascular complications – are markedly higher with the COVID-19 infection than with the vaccines,” she said.

It also adds a new twist to the search for the mechanisms of myocarditis, which has focused on the immunogenicity of the RNA in the Pfizer and Moderna vaccines but also hypothesized that molecular mimicry between the SARS-CoV-2 spike glycoprotein and cell antigens, antibody production against cardiac proteins, and testosterone may play a role.

“But now it doesn’t look like the risk is solely confined to the mRNA vaccine platform because it’s also happening with the adenovirus,” Dr. Bozkurt said. “The mechanisms require future experimental and clinical research and we’ll need more granular data with cohorts that are closely followed up as well as subclinical follow-up.”

James de Lemos, MD, professor of medicine at the University of Texas Southwestern Medical Center, Dallas, and cochair of the American Heart Association’s COVID-19 CVD Registry, said he was also not surprised by a myocarditis signal with AstraZeneca’s adenovirus vaccine.

“Looking at relative risks has biological implications, but the clinical and public health implications are that the absolute risk with the adenovirus is trivial. And you see that with their estimations of absolute risk where it’s literally sort of a needle in the haystack of 1 or 2 per million,” he said in an interview.
 

Large-scale data

The investigators examined the rates of hospital admission or death from myocarditis, pericarditis, and cardiac arrhythmia in the 28 days following SARS-CoV-2 vaccination or infection by linking the English National Immunisation Database of COVID-19 vaccination with a national patient-level health care database of 38.6 million people, aged 16 years or older, vaccinated from Dec.1, 2020, to Aug. 24, 2021.

The number of people admitted to the hospital or who died during the study period was 1,615 for myocarditis, 1,574 for pericarditis, and 385,508 for cardiac arrhythmia.

There was no evidence of an increased risk for pericarditis or cardiac arrhythmia following vaccination, except for arrhythmia in the 28 days following a second dose of the Moderna vaccine (IRR, 1.46).

In contrast, the risk was increased for pericarditis (IRR, 2.79) and cardiac arrhythmia (IRR, 5.35) in the 28 days following a positive SARS-CoV-2 test result.

Although the scale of the analysis allows for more precise estimates than what’s been possible in smaller data sets, there is the challenge of diagnosing COVID-19 from billing codes and the potential for ascertainment bias, noted Dr. de Lemos.  

“Having said that, I think it’s a really important study, because it’s the first study to put the incidence in context in the same general population the risks of myocarditis with various vaccines and with COVID-19,” he said.

“That’s really important and provides a lot of reassurance for those who are trying to balance the risks and benefits of vaccination.”
 

Analyses by sex and age

A subgroup analysis by age showed increased risks for myocarditis with the mRNA vaccines only in those younger than 40, whereas no association was found with the Oxford adenovirus vaccine.

“We’re not seeing any signal here that would make us change the recommendation for vaccination in children as a consequence of this risk,” Dr. Mills said during a press briefing.

Dr. Bozkurt pointed out, however, that the estimated excess in myocarditis events following a second dose of the Moderna vaccine in these younger adults reportedly exceeded that for SARS-CoV-2 infection (15 per million vs. 10 per million).

“For that age group, it’s concerning and needs further clarification. This hasn’t been seen before,” she said.

The average age was 39 years for those receiving two doses of the Moderna vaccine and 55 for recipients of the Pfizer and Oxford vaccines. The Moderna vaccine wasn’t rolled out until April 2021 in the United Kingdom, the authors noted, so the number of patients who received this vaccine is lower.

Although reports have suggested young males are at greater risk for myocarditis after vaccination, an analysis by sex found that women had an increased risk for myocarditis after a first dose of the AstraZeneca (IRR, 1.40) and Pfizer (IRR, 1.54) vaccines and following a positive COVID-19 test result (IRR, 11.00).

“Women being at increased risk is rather a new message,” Dr. Bozkurt said. “But the incidence rate ratios are being compared against the unvaccinated, so when you see the increase in women, it doesn’t mean it’s increased against men. It would be helpful for sex-specific incidence rate ratios to be reported for younger age subgroups, such as ages 16-20 and 20-30, to determine whether there’s an increased risk for males compared to females at younger ages.”

Age and sex differences are huge questions, but “I think we’ll learn a lot about myocarditis in general from what is going to be an explosion of research into the vaccine-associated causes,” Dr. de Lemos said.

“That will help us understand myocarditis more broadly and prepare us for the next generation of vaccines, which inevitably will be mRNA based.”

Dr. Mills reported having no relevant disclosures. Dr. Bozkurt reported consulting for Bayer and scPharmaceuticals and serving on a clinical-events committee for a trial supported by Abbott Pharmaceuticals and on a data and safety monitoring board for a trial supported by Liva Nova Pharmaceuticals. Dr. De Lemos reported having no relevant conflicts of interest.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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

Advances in technology and genomics have given rise to many issues, such as the extent to which genetic and lifestyle factors contribute to the individual-level risk for coronary artery disease, and the extent one’s genetic risk can be offset by a healthy lifestyle.

Mount Sinai Heart/CCA 3.0

Over the years, Valentin Fuster, MD, PhD, director of Mount Sinai Heart and physician-in-chief at the Mount Sinai Hospital, both in New York, has focused much of his research on this topic. At the virtual ACC Latin America 2021 conference, the cardiologist spoke about his hypotheses and findings during his opening plenary on imaging genomics, an emerging field that is rapidly identifying genes that influence the brain, cognition, and risk for disease.

Dr. Fuster discussed his research (J Am Coll Cardiol. 2021;77:2777-91; J Am Coll Cardiol. 2020;75:1617-27; J Am Coll Cardiol. 2019;73:1371-82; J Am Coll Cardiol. 2017;70:2979-91; Circulation. 2015;131:2104-13) and spoke about his innovative program that looks at cardiovascular health in people from young children to senior citizens. The work has been a process of learning and discovery. “We’re beginning to understand how the disease can develop earlier and how we can prevent it from getting worse. There’s nothing more beneficial than beginning to see how the disease starts in the arteries – something that we’re able to do with imaging technologies that, in the next 2 years, will be available worldwide.” And “by using imaging biomarkers in conjunction with genomic biomarkers, we’re beginning to get an idea earlier on as to whether the person is at risk.”

We need to be talking more about health and healthy arteries and trying to come up with epistemologies that are more modern, Dr. Fuster said. “To be able to see who we actually are is fascinating, and all of this is completely new” with imaging genomics.

Developing cardiovascular disease can be identified in people aged 40-60 years when seven risk factors – obesity, metabolic syndrome, blood pressure, diabetes, smoking, sedentary lifestyle, and poor nutrition” – are grouped together, he explained. In their 2015 study, Dr. Fuster and colleagues explored, using high-quality three-dimensional ultrasonography, five areas of the body – right and left carotids, aorta, and right and left iliofemorals – in more than 4,000 people with no history of cardiovascular disease.

“The first thing I want to point out is that the disease originates in a territory that is not commonly evaluated. And we had no idea. We only learned about this development through imaging tests, assessing plaques. The disease starts in the femoral artery and, in fact, it starts with an inflammatory process – seen at autopsy – that can lead to fibrosis and, in later years, can form lipid-rich vulnerable plaque,” he said.

His work has shown an increase in disease progression in groups of people who have been monitored for 20 years. What is most interesting is the way lesions are silent and evolve as the years go by.

“Atherosclerosis appears as a silent phenomenon initially and worsens in the presence of risk factors that trigger its progression,” he said.

But can subclinical disease be identified in people who have few or no risk factors? “What we call normal is not, in fact, normal,” said Dr. Fuster. To not have subclinical disease, LDL cholesterol needs to be 70 mg/dL and hemoglobin A1c needs to be 5%-6%, according to a 2020 study by Dr. Fuster and colleagues.

“The fact that we’re seeing people with no apparent risk factors develop atherosclerosis is the reason what we consider normal is not,” he said. It is necessary to take into account what happened in the first 40 years of these individuals’ lives, he added.

Dr. Fuster presented findings on 6,000 people aged 60-100 years underwent three-dimensional ultrasonography and were monitored for 12 years. The data have yet to be published, but they indicate that, with this disease, more than just risk factors are at play; atherosclerosis is related to what happens early on in one’s life.

In their 2016 study of more than 55,000 participants, Dr. Fuster and associates quantified the genetic risk for coronary artery disease with a polygenic risk score derived from an analysis of up to 50 genetic polymorphisms that had been associated with coronary artery disease in previous studies. On the basis of this score, the participants were divided into subgroups by genetic risk: low, intermediate, and high. Genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease. For participants at high genetic risk, a favorable lifestyle was associated with a relative risk for coronary artery disease nearly 50% lower than an unfavorable lifestyle.

The risk factors cause the bone marrow to be activated and, when this happens, an inflammatory process occurs in the arteries. This activation is a defense mechanism designed to help monocytes heal the arteries. “When we’re dealing with a disease in the arteries, inflammation starts in the bone marrow, where cholesterol is deposited, and there are macrophages that, because there’s too much to clean up and they can’t keep up, will actually kill themselves. When that happens, they will release substances that will damage the arteries,” Dr. Fuster reported.

In elderly people, risk factors have an impact not only on the great vessels, they can also lead to cerebral small vessel disease.

“The problem is that, before, we didn’t have the technology to make this observation. And this is something critical with respect to late-onset dementia,” he said, citing a 2016 study on Alzheimer’s disease. Even if risk factors are increasing, the person will not necessarily develop the disease, but there is a greater chance that they will.
 

Education

Playful activities have a major impact in childhood. With this in mind, Dr. Fuster instituted a 6-month, 60-hour educational program for children aged 3-6 years. The approach was aimed at teaching children about healthy eating habits and how the human body works. “Children are able to absorb everything we say, but then at age 10, it all goes away,” he said. With another intervention that involved the same children, he showed that the benefits were greater than those seen in the first intervention.

“Our hypothesis is that, regardless of age, any program that has to do with prevention needs to be repeated,” Dr. Fuster said. “Repetition will bring more benefits every x years. That’s what we’re learning.

“We learned that when these children go home, they tell their parents what to do. The program had a greater impact on the children than their parents. So we need to use repetition in prevention efforts directed at young children. And we need to remember that the later we start this kind of work, the less impact it will have. The sooner things start, the greater the benefit and the lower the cost,” he concluded.

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