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In an observational study of more than 90,000 U.S. health care professionals, consuming even a small amount of olive oil was associated with reduced total mortality.

Compared with men and women who rarely or never consumed olive oil (the lowest intake), those who consumed greater than 0.5 tablespoon/day or more than 7 g/day (the highest intake) had a 19% lower mortality risk over a 28-year follow-up, starting from an average age of 56 years.

Moreover, compared with those with the lowest olive oil intake, those with the highest intake had a 19% lower cardiovascular disease (CVD) mortality, a 17% lower risk of dying from cancer, a 29% lower risk of dying from neurodegenerative disease, and an 18% lower risk of dying from respiratory disease during follow-up.

masa44/iStock/Getty Images

The researchers estimate that replacing 10 g/day of margarine, butter, mayonnaise, or dairy fat with the same amount of olive oil is associated with an 8%-34% lower risk of death from various causes.

The study by Marta Guasch-Ferré, PhD, and colleagues was published online Jan. 10 in the Journal of the American College of Cardiology.
 

Results support plant-based dietary fat recommendations

“Our results support current dietary recommendations to increase the intake of olive oil and other unsaturated vegetable oils in place of other fats to improve overall health and longevity,” the researchers summarize.

However, “I wouldn’t say that olive oil is the only way to help you live longer,” Dr. Guasch-Ferré, a senior research scientist in the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, cautioned in an interview with this news organization.

“Other things are very important, such as not smoking, doing physical activity, etc., but one recommendation could be to try to eat more plant-based food including olive oil and healthy fat,” she added, and to use it for cooking, salad dressing, and baking, and substitute it for saturated fat or animal fat, especially for cooking.

The study suggests that people should “consume a more plant-based diet and prioritize fatty acids such as olive oil because they have a better nutritional composition (high in phenols and antioxidants), instead of using butter or margarines or other animal fats that have been shown to have detrimental effects for health,” she added, which is consistent with recommendations in the Dietary Guidelines for Americans.

“That said,” Dr. Guasch-Ferré summarized, “replication is needed in other cohorts and populations to see if the results are similar.”

In an accompanying editorial, Susanna C. Larsson, PhD, writes that “this was a well-designed study, with long-term follow-up and repeated measurements of dietary intake and other risk factors for diseases.”

“However, the difference in olive oil consumption between those with the highest and those with the lowest/no olive oil consumption was very low (0.5 tablespoon) and a [12%] reduced mortality risk was observed already at a much lower intake (0.5 teaspoon, about 1.5 g/day) of olive oil,” she noted in an email to this news organization.

“It’s a bit hard to believe that such a small amount could have an independent effect on mortality risk,” Dr. Larsson, associate professor of epidemiology at the Karolinska Institutet, Stockholm, cautioned.

Like Dr. Guasch-Ferré, she noted that “just adding one or two teaspoons of olive oil to the diet each day will likely not change the risk of mortality.”

Rather, “people may need to make larger changes in the whole diet, not focus on fat only. An overall healthier diet, rich in nonrefined plant-based foods (vegetables, whole grains, nuts), low/no intake of processed foods, and a switch to healthier fat (eg, olive oil) is needed.”

Importantly, “this study cannot say anything about causality, that is, whether it’s olive oil specifically that reduces mortality risk or if there are many other beneficial factors that act together to reduce mortality rate among those with high olive oil consumption.”

The researchers acknowledge this observational study limitation and that the findings may not be generalizable to other populations.
 

Novel findings regarding Alzheimer’s and respiratory disease

Dr. Larsson highlights two novel findings of this study.

First, it showed a 27% reduction in risk of dementia-related mortality for those in the highest versus lowest category of olive oil consumption. “Considering the lack of preventive strategies for Alzheimer’s disease and the high morbidity and mortality related to this disease, this finding, if confirmed, is of great public health importance,” she said.

Second, the study reported an inverse association of olive oil consumption with risk of respiratory disease mortality. “Because residual confounding from smoking cannot be ruled out,” Dr. Larsson said, “this finding is tentative and requires confirmation in a study that is less susceptible to confounding, such as a randomized trial.”

And although the current study and previous studies have found that consumption of olive oil may have health benefits, she identified several remaining questions.

“Are the associations causal or spurious?” she noted. Is olive oil consumption protective for certain cardiovascular diseases like stroke or atrial fibrillation only, as has been shown in other studies, or also for other major diseases and causes of death, she added. What is the amount of olive oil required for a protective effect?

Further, is the potential effect related to monounsaturated fatty acids (MUFAs) or phenolic compounds; that is, “is the protective effect confined to polyphenol-rich extra-virgin olive oil or are refined olive oil and other vegetable oils as beneficial? More research is needed to address these questions,” she concludes.

“Further studies are needed,” the researchers agree, “to confirm the association of olive oil consumption with reduced mortality, clarify the mechanisms responsible, and quantify the dose/volume boundaries around this effect.”  
 

Virgin olive oil has more polyphenols

Olive oil, a key component of the Mediterranean diet, is high in MUFAs, especially oleic acid, as well as vitamin E and polyphenols, which contribute to its anti-inflammatory and antioxidant properties, the researchers explain.

Virgin olive oil, produced by mechanically pressing ripe olives, contains multiple bioactive and antioxidant components and has an acidity of less than 1.5%. And extra-virgin olive oil is produced the same way but has a higher quality, more intense taste, and lower acidity (less than 1%).

Refined or processed olive oil contains less phytochemicals, as some are lost during processing; it usually contains more than 80% refined oil, plus virgin oil added back to enhance flavor, and may also be labeled “pure” or “light.” However, refined olive oil “still has a good amount of healthy fatty acids but less bioactive compounds,” Dr. Guasch-Ferré noted.

Until now, no large prospective study has examined the link between olive oil intake and all-cause and cause-specific mortality in a U.S. population, where olive oil consumption is limited, compared with Mediterranean countries.

The researchers identified 60,582 women in the Nurses’ Health Study and 31,801 men in the Health Professionals Follow-up Study who were free of CVD or cancer in 1990, the first year that food frequency questionnaires in these studies asked about olive oil.

Participants replied to questionnaires every 4 years that asked about use of olive oil (for salad dressing, baking, frying, sautéing, and spreading on bread), other vegetable oils (for example, corn, safflower, soybean, canola oil), margarine, butter, and dairy fat. The researchers averaged the consumption of these fats during the follow-up years.

From 1990 to 2019, the average consumption of olive oil increased from 1.6 g/day to 4 g/day. Margarine in the 1990s contained saturated fat and trans fats, whereas more recently margarine contains beneficial olive oil or vegetable fat, Dr. Guasch-Ferré noted.

Baseline olive oil consumption in this U.S. population “differed remarkably” from that in the Spanish population in the PREDIMED (Prevención con Dieta Mediterránea) trial, which was, on average, 20-22 g/day of extra-virgin olive oil and 16-18 g/day of refined/mixed olive oil, Larsson pointed out.

Because olive oil consumption was so low in this U.S. study, the researchers did not distinguish between virgin/extra-virgin olive oil and refined/processed olive oil.

The participants were almost all White (99%) and were generally healthier than the average U.S. population; on average, they had a body mass index of 25.3-25.8 kg/m² and ate 4.8-7.2 fruits and vegetables/day.

Those with the highest olive oil consumption were more physically active, had a healthier diet, were more likely to have Southern European or Mediterranean ancestry, and were less likely to smoke.

During 28 years of follow-up, 36,856 participants died. The researchers classified the deaths into five categories: CVD, cancer, neurodegenerative disease (including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis), respiratory disease (such as chronic obstructive pulmonary disease), and all other causes (including suicide, injury, infections, diabetes, and kidney disease).

After adjusting for multiple confounders, compared with participants who rarely or never consumed olive oil, those in the highest quartile for olive oil consumption had a decreased risk of death from all causes (hazard ratio, 0.81; 95% confidence interval, 0.78 - 0.84) and from CVD (HR, 0.81; 95% CI, 0.75-0.87), cancer (HR, 0.83; 95% CI, 0.78-0.89), neurodegenerative disease (HR, 0.71; 95% CI, 0.64-0.78), and respiratory disease (HR, 0.82; 95% CI, 0.72-0.93). 

There was no decrease in mortality in models where the researchers substituted olive oil for vegetable oil, suggesting that vegetable oils may provide similar health benefits as olive oil.

The research was supported by grants from the National Institutes of Health. Dr. Guasch-Ferré was supported by the American Diabetes Association. Coauthor Salas-Salvadó is partially supported by the Catalan Institution for Research and Advanced Studies and received the virgin olive oil that was used in the PREDIMED and PREDIMED-Plus studies from the Patrimonio Communal Olivalero and Hojiblanca (Málaga, Spain). The other study authors and Dr. Larsson have reported no relevant financial relationships.

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

In an observational study of more than 90,000 U.S. health care professionals, consuming even a small amount of olive oil was associated with reduced total mortality.

Compared with men and women who rarely or never consumed olive oil (the lowest intake), those who consumed greater than 0.5 tablespoon/day or more than 7 g/day (the highest intake) had a 19% lower mortality risk over a 28-year follow-up, starting from an average age of 56 years.

Moreover, compared with those with the lowest olive oil intake, those with the highest intake had a 19% lower cardiovascular disease (CVD) mortality, a 17% lower risk of dying from cancer, a 29% lower risk of dying from neurodegenerative disease, and an 18% lower risk of dying from respiratory disease during follow-up.

masa44/iStock/Getty Images

The researchers estimate that replacing 10 g/day of margarine, butter, mayonnaise, or dairy fat with the same amount of olive oil is associated with an 8%-34% lower risk of death from various causes.

The study by Marta Guasch-Ferré, PhD, and colleagues was published online Jan. 10 in the Journal of the American College of Cardiology.
 

Results support plant-based dietary fat recommendations

“Our results support current dietary recommendations to increase the intake of olive oil and other unsaturated vegetable oils in place of other fats to improve overall health and longevity,” the researchers summarize.

However, “I wouldn’t say that olive oil is the only way to help you live longer,” Dr. Guasch-Ferré, a senior research scientist in the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, cautioned in an interview with this news organization.

“Other things are very important, such as not smoking, doing physical activity, etc., but one recommendation could be to try to eat more plant-based food including olive oil and healthy fat,” she added, and to use it for cooking, salad dressing, and baking, and substitute it for saturated fat or animal fat, especially for cooking.

The study suggests that people should “consume a more plant-based diet and prioritize fatty acids such as olive oil because they have a better nutritional composition (high in phenols and antioxidants), instead of using butter or margarines or other animal fats that have been shown to have detrimental effects for health,” she added, which is consistent with recommendations in the Dietary Guidelines for Americans.

“That said,” Dr. Guasch-Ferré summarized, “replication is needed in other cohorts and populations to see if the results are similar.”

In an accompanying editorial, Susanna C. Larsson, PhD, writes that “this was a well-designed study, with long-term follow-up and repeated measurements of dietary intake and other risk factors for diseases.”

“However, the difference in olive oil consumption between those with the highest and those with the lowest/no olive oil consumption was very low (0.5 tablespoon) and a [12%] reduced mortality risk was observed already at a much lower intake (0.5 teaspoon, about 1.5 g/day) of olive oil,” she noted in an email to this news organization.

“It’s a bit hard to believe that such a small amount could have an independent effect on mortality risk,” Dr. Larsson, associate professor of epidemiology at the Karolinska Institutet, Stockholm, cautioned.

Like Dr. Guasch-Ferré, she noted that “just adding one or two teaspoons of olive oil to the diet each day will likely not change the risk of mortality.”

Rather, “people may need to make larger changes in the whole diet, not focus on fat only. An overall healthier diet, rich in nonrefined plant-based foods (vegetables, whole grains, nuts), low/no intake of processed foods, and a switch to healthier fat (eg, olive oil) is needed.”

Importantly, “this study cannot say anything about causality, that is, whether it’s olive oil specifically that reduces mortality risk or if there are many other beneficial factors that act together to reduce mortality rate among those with high olive oil consumption.”

The researchers acknowledge this observational study limitation and that the findings may not be generalizable to other populations.
 

Novel findings regarding Alzheimer’s and respiratory disease

Dr. Larsson highlights two novel findings of this study.

First, it showed a 27% reduction in risk of dementia-related mortality for those in the highest versus lowest category of olive oil consumption. “Considering the lack of preventive strategies for Alzheimer’s disease and the high morbidity and mortality related to this disease, this finding, if confirmed, is of great public health importance,” she said.

Second, the study reported an inverse association of olive oil consumption with risk of respiratory disease mortality. “Because residual confounding from smoking cannot be ruled out,” Dr. Larsson said, “this finding is tentative and requires confirmation in a study that is less susceptible to confounding, such as a randomized trial.”

And although the current study and previous studies have found that consumption of olive oil may have health benefits, she identified several remaining questions.

“Are the associations causal or spurious?” she noted. Is olive oil consumption protective for certain cardiovascular diseases like stroke or atrial fibrillation only, as has been shown in other studies, or also for other major diseases and causes of death, she added. What is the amount of olive oil required for a protective effect?

Further, is the potential effect related to monounsaturated fatty acids (MUFAs) or phenolic compounds; that is, “is the protective effect confined to polyphenol-rich extra-virgin olive oil or are refined olive oil and other vegetable oils as beneficial? More research is needed to address these questions,” she concludes.

“Further studies are needed,” the researchers agree, “to confirm the association of olive oil consumption with reduced mortality, clarify the mechanisms responsible, and quantify the dose/volume boundaries around this effect.”  
 

Virgin olive oil has more polyphenols

Olive oil, a key component of the Mediterranean diet, is high in MUFAs, especially oleic acid, as well as vitamin E and polyphenols, which contribute to its anti-inflammatory and antioxidant properties, the researchers explain.

Virgin olive oil, produced by mechanically pressing ripe olives, contains multiple bioactive and antioxidant components and has an acidity of less than 1.5%. And extra-virgin olive oil is produced the same way but has a higher quality, more intense taste, and lower acidity (less than 1%).

Refined or processed olive oil contains less phytochemicals, as some are lost during processing; it usually contains more than 80% refined oil, plus virgin oil added back to enhance flavor, and may also be labeled “pure” or “light.” However, refined olive oil “still has a good amount of healthy fatty acids but less bioactive compounds,” Dr. Guasch-Ferré noted.

Until now, no large prospective study has examined the link between olive oil intake and all-cause and cause-specific mortality in a U.S. population, where olive oil consumption is limited, compared with Mediterranean countries.

The researchers identified 60,582 women in the Nurses’ Health Study and 31,801 men in the Health Professionals Follow-up Study who were free of CVD or cancer in 1990, the first year that food frequency questionnaires in these studies asked about olive oil.

Participants replied to questionnaires every 4 years that asked about use of olive oil (for salad dressing, baking, frying, sautéing, and spreading on bread), other vegetable oils (for example, corn, safflower, soybean, canola oil), margarine, butter, and dairy fat. The researchers averaged the consumption of these fats during the follow-up years.

From 1990 to 2019, the average consumption of olive oil increased from 1.6 g/day to 4 g/day. Margarine in the 1990s contained saturated fat and trans fats, whereas more recently margarine contains beneficial olive oil or vegetable fat, Dr. Guasch-Ferré noted.

Baseline olive oil consumption in this U.S. population “differed remarkably” from that in the Spanish population in the PREDIMED (Prevención con Dieta Mediterránea) trial, which was, on average, 20-22 g/day of extra-virgin olive oil and 16-18 g/day of refined/mixed olive oil, Larsson pointed out.

Because olive oil consumption was so low in this U.S. study, the researchers did not distinguish between virgin/extra-virgin olive oil and refined/processed olive oil.

The participants were almost all White (99%) and were generally healthier than the average U.S. population; on average, they had a body mass index of 25.3-25.8 kg/m² and ate 4.8-7.2 fruits and vegetables/day.

Those with the highest olive oil consumption were more physically active, had a healthier diet, were more likely to have Southern European or Mediterranean ancestry, and were less likely to smoke.

During 28 years of follow-up, 36,856 participants died. The researchers classified the deaths into five categories: CVD, cancer, neurodegenerative disease (including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis), respiratory disease (such as chronic obstructive pulmonary disease), and all other causes (including suicide, injury, infections, diabetes, and kidney disease).

After adjusting for multiple confounders, compared with participants who rarely or never consumed olive oil, those in the highest quartile for olive oil consumption had a decreased risk of death from all causes (hazard ratio, 0.81; 95% confidence interval, 0.78 - 0.84) and from CVD (HR, 0.81; 95% CI, 0.75-0.87), cancer (HR, 0.83; 95% CI, 0.78-0.89), neurodegenerative disease (HR, 0.71; 95% CI, 0.64-0.78), and respiratory disease (HR, 0.82; 95% CI, 0.72-0.93). 

There was no decrease in mortality in models where the researchers substituted olive oil for vegetable oil, suggesting that vegetable oils may provide similar health benefits as olive oil.

The research was supported by grants from the National Institutes of Health. Dr. Guasch-Ferré was supported by the American Diabetes Association. Coauthor Salas-Salvadó is partially supported by the Catalan Institution for Research and Advanced Studies and received the virgin olive oil that was used in the PREDIMED and PREDIMED-Plus studies from the Patrimonio Communal Olivalero and Hojiblanca (Málaga, Spain). The other study authors and Dr. Larsson have reported no relevant financial relationships.

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

In an observational study of more than 90,000 U.S. health care professionals, consuming even a small amount of olive oil was associated with reduced total mortality.

Compared with men and women who rarely or never consumed olive oil (the lowest intake), those who consumed greater than 0.5 tablespoon/day or more than 7 g/day (the highest intake) had a 19% lower mortality risk over a 28-year follow-up, starting from an average age of 56 years.

Moreover, compared with those with the lowest olive oil intake, those with the highest intake had a 19% lower cardiovascular disease (CVD) mortality, a 17% lower risk of dying from cancer, a 29% lower risk of dying from neurodegenerative disease, and an 18% lower risk of dying from respiratory disease during follow-up.

masa44/iStock/Getty Images

The researchers estimate that replacing 10 g/day of margarine, butter, mayonnaise, or dairy fat with the same amount of olive oil is associated with an 8%-34% lower risk of death from various causes.

The study by Marta Guasch-Ferré, PhD, and colleagues was published online Jan. 10 in the Journal of the American College of Cardiology.
 

Results support plant-based dietary fat recommendations

“Our results support current dietary recommendations to increase the intake of olive oil and other unsaturated vegetable oils in place of other fats to improve overall health and longevity,” the researchers summarize.

However, “I wouldn’t say that olive oil is the only way to help you live longer,” Dr. Guasch-Ferré, a senior research scientist in the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, cautioned in an interview with this news organization.

“Other things are very important, such as not smoking, doing physical activity, etc., but one recommendation could be to try to eat more plant-based food including olive oil and healthy fat,” she added, and to use it for cooking, salad dressing, and baking, and substitute it for saturated fat or animal fat, especially for cooking.

The study suggests that people should “consume a more plant-based diet and prioritize fatty acids such as olive oil because they have a better nutritional composition (high in phenols and antioxidants), instead of using butter or margarines or other animal fats that have been shown to have detrimental effects for health,” she added, which is consistent with recommendations in the Dietary Guidelines for Americans.

“That said,” Dr. Guasch-Ferré summarized, “replication is needed in other cohorts and populations to see if the results are similar.”

In an accompanying editorial, Susanna C. Larsson, PhD, writes that “this was a well-designed study, with long-term follow-up and repeated measurements of dietary intake and other risk factors for diseases.”

“However, the difference in olive oil consumption between those with the highest and those with the lowest/no olive oil consumption was very low (0.5 tablespoon) and a [12%] reduced mortality risk was observed already at a much lower intake (0.5 teaspoon, about 1.5 g/day) of olive oil,” she noted in an email to this news organization.

“It’s a bit hard to believe that such a small amount could have an independent effect on mortality risk,” Dr. Larsson, associate professor of epidemiology at the Karolinska Institutet, Stockholm, cautioned.

Like Dr. Guasch-Ferré, she noted that “just adding one or two teaspoons of olive oil to the diet each day will likely not change the risk of mortality.”

Rather, “people may need to make larger changes in the whole diet, not focus on fat only. An overall healthier diet, rich in nonrefined plant-based foods (vegetables, whole grains, nuts), low/no intake of processed foods, and a switch to healthier fat (eg, olive oil) is needed.”

Importantly, “this study cannot say anything about causality, that is, whether it’s olive oil specifically that reduces mortality risk or if there are many other beneficial factors that act together to reduce mortality rate among those with high olive oil consumption.”

The researchers acknowledge this observational study limitation and that the findings may not be generalizable to other populations.
 

Novel findings regarding Alzheimer’s and respiratory disease

Dr. Larsson highlights two novel findings of this study.

First, it showed a 27% reduction in risk of dementia-related mortality for those in the highest versus lowest category of olive oil consumption. “Considering the lack of preventive strategies for Alzheimer’s disease and the high morbidity and mortality related to this disease, this finding, if confirmed, is of great public health importance,” she said.

Second, the study reported an inverse association of olive oil consumption with risk of respiratory disease mortality. “Because residual confounding from smoking cannot be ruled out,” Dr. Larsson said, “this finding is tentative and requires confirmation in a study that is less susceptible to confounding, such as a randomized trial.”

And although the current study and previous studies have found that consumption of olive oil may have health benefits, she identified several remaining questions.

“Are the associations causal or spurious?” she noted. Is olive oil consumption protective for certain cardiovascular diseases like stroke or atrial fibrillation only, as has been shown in other studies, or also for other major diseases and causes of death, she added. What is the amount of olive oil required for a protective effect?

Further, is the potential effect related to monounsaturated fatty acids (MUFAs) or phenolic compounds; that is, “is the protective effect confined to polyphenol-rich extra-virgin olive oil or are refined olive oil and other vegetable oils as beneficial? More research is needed to address these questions,” she concludes.

“Further studies are needed,” the researchers agree, “to confirm the association of olive oil consumption with reduced mortality, clarify the mechanisms responsible, and quantify the dose/volume boundaries around this effect.”  
 

Virgin olive oil has more polyphenols

Olive oil, a key component of the Mediterranean diet, is high in MUFAs, especially oleic acid, as well as vitamin E and polyphenols, which contribute to its anti-inflammatory and antioxidant properties, the researchers explain.

Virgin olive oil, produced by mechanically pressing ripe olives, contains multiple bioactive and antioxidant components and has an acidity of less than 1.5%. And extra-virgin olive oil is produced the same way but has a higher quality, more intense taste, and lower acidity (less than 1%).

Refined or processed olive oil contains less phytochemicals, as some are lost during processing; it usually contains more than 80% refined oil, plus virgin oil added back to enhance flavor, and may also be labeled “pure” or “light.” However, refined olive oil “still has a good amount of healthy fatty acids but less bioactive compounds,” Dr. Guasch-Ferré noted.

Until now, no large prospective study has examined the link between olive oil intake and all-cause and cause-specific mortality in a U.S. population, where olive oil consumption is limited, compared with Mediterranean countries.

The researchers identified 60,582 women in the Nurses’ Health Study and 31,801 men in the Health Professionals Follow-up Study who were free of CVD or cancer in 1990, the first year that food frequency questionnaires in these studies asked about olive oil.

Participants replied to questionnaires every 4 years that asked about use of olive oil (for salad dressing, baking, frying, sautéing, and spreading on bread), other vegetable oils (for example, corn, safflower, soybean, canola oil), margarine, butter, and dairy fat. The researchers averaged the consumption of these fats during the follow-up years.

From 1990 to 2019, the average consumption of olive oil increased from 1.6 g/day to 4 g/day. Margarine in the 1990s contained saturated fat and trans fats, whereas more recently margarine contains beneficial olive oil or vegetable fat, Dr. Guasch-Ferré noted.

Baseline olive oil consumption in this U.S. population “differed remarkably” from that in the Spanish population in the PREDIMED (Prevención con Dieta Mediterránea) trial, which was, on average, 20-22 g/day of extra-virgin olive oil and 16-18 g/day of refined/mixed olive oil, Larsson pointed out.

Because olive oil consumption was so low in this U.S. study, the researchers did not distinguish between virgin/extra-virgin olive oil and refined/processed olive oil.

The participants were almost all White (99%) and were generally healthier than the average U.S. population; on average, they had a body mass index of 25.3-25.8 kg/m² and ate 4.8-7.2 fruits and vegetables/day.

Those with the highest olive oil consumption were more physically active, had a healthier diet, were more likely to have Southern European or Mediterranean ancestry, and were less likely to smoke.

During 28 years of follow-up, 36,856 participants died. The researchers classified the deaths into five categories: CVD, cancer, neurodegenerative disease (including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis), respiratory disease (such as chronic obstructive pulmonary disease), and all other causes (including suicide, injury, infections, diabetes, and kidney disease).

After adjusting for multiple confounders, compared with participants who rarely or never consumed olive oil, those in the highest quartile for olive oil consumption had a decreased risk of death from all causes (hazard ratio, 0.81; 95% confidence interval, 0.78 - 0.84) and from CVD (HR, 0.81; 95% CI, 0.75-0.87), cancer (HR, 0.83; 95% CI, 0.78-0.89), neurodegenerative disease (HR, 0.71; 95% CI, 0.64-0.78), and respiratory disease (HR, 0.82; 95% CI, 0.72-0.93). 

There was no decrease in mortality in models where the researchers substituted olive oil for vegetable oil, suggesting that vegetable oils may provide similar health benefits as olive oil.

The research was supported by grants from the National Institutes of Health. Dr. Guasch-Ferré was supported by the American Diabetes Association. Coauthor Salas-Salvadó is partially supported by the Catalan Institution for Research and Advanced Studies and received the virgin olive oil that was used in the PREDIMED and PREDIMED-Plus studies from the Patrimonio Communal Olivalero and Hojiblanca (Málaga, Spain). The other study authors and Dr. Larsson have reported no relevant financial relationships.

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

The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.

The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)

Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.

The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.

Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.

Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.

The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.

Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.

Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.

The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.

Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.

“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.

Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.

“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.

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

The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.

The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)

Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.

The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.

Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.

Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.

The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.

Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.

Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.

The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.

Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.

“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.

Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.

“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.

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

The United States reported 1.35 million new COVID-19 cases on Jan. 10, logging the highest daily total for any country in the world during the pandemic.

The United States set the previous record of 1 million cases on Jan. 3. (A large number of cases are reported on Mondays, since many states don’t provide updates over the weekend, according to Reuters.)

Still, the 7-day average for new cases has surpassed 700,000, tripling in 2 weeks as the contagious Omicron variant continues to spread across the country.

The daily record of new cases came a day after the United States crossed the grim milestone of 60 million COVID-19 cases during the pandemic, according to the latest data from Johns Hopkins University. More than 11 million new cases were reported in the past 28 days, with 5 million reported since Jan. 2.

Globally, more than 310 million cases have been reported, resulting in nearly 5.5 million COVID-19 deaths. Almost 40 million cases have been confirmed worldwide during the past month, with the United States accounting for 28% of those.

Texas became the second state to report more than 5 million cases since the pandemic began, behind California’s total of 6 million cases. Florida has reported more than 4.6 million, while New York has reported more than 4.1 million.

The United States has also hit an all-time high for hospitalizations, with nearly 146,000 COVID-19 patients in hospitals across the country, according to the latest data from the U.S. Department of Health and Human Services. The previous record was 142,000 hospitalizations in January 2021.

Jan. 11’s hospitalizations are more than twice as many as 2 weeks ago, according to CNN. About 78% of inpatient beds are in use nationwide, and 21% are being used for COVID-19 patients.

Deaths are averaging about 1,700 per day, Reuters reported, which is up from 1,400 in recent days but not much higher than earlier this winter. The peak average was 3,400 daily deaths in mid-January 2021.

The surging numbers of cases and hospitalizations across the country are straining hospitals. On Jan. 10, Virginia Gov. Ralph Northam declared a state of emergency after the number of intensive care unit hospitalizations more than doubled since Dec. 1, CNN reported. The order allows hospitals to expand bed capacity, use telehealth options, and be more flexible with staffing.

Texas is hiring at least 2,700 medical staff to help with the surge, CNN reported, and Kentucky has mobilized the National Guard to provide support.

“Omicron continues to burn through the commonwealth, growing at levels we have never seen before. Omicron is significantly more contagious than even the Delta variant,” Kentucky Gov. Andy Beshear said during a news briefing Jan. 10.

Kentucky reported its highest weekly total of cases last week and has its highest rate of positive tests, at 26%. Mr. Beshear said the state is down to 134 available adult ICU beds.

“If it spreads at the rate we are seeing, it is certainly going to fill up our hospitals,” he said.

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

Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.

Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.

Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.

The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.

Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.

“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”

The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.

Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
 

Fewer in intensive group hit target

The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).

The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).

Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).

Rates of adverse and serious adverse events were similar between the groups.

The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.

“However, improved erosion scores were not observed in this study,” the authors noted.

The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.

They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
 

Pegloticase not available outside United States

However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.

Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
 

Managing gout is a long-term process

Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.

“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.

He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.

He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”

He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.

“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.

It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.

“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.

The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”

Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.

Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.

Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.

Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.

The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.

Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.

“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”

The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.

Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
 

Fewer in intensive group hit target

The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).

The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).

Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).

Rates of adverse and serious adverse events were similar between the groups.

The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.

“However, improved erosion scores were not observed in this study,” the authors noted.

The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.

They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
 

Pegloticase not available outside United States

However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.

Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
 

Managing gout is a long-term process

Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.

“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.

He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.

He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”

He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.

“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.

It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.

“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.

The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”

Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.

Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.

Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.

Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.

The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.

Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.

“It is reassuring that the approach of treating to target is a good approach,” Dr. Gaffo said. “The very, very low targets were not better than the [standard target].”

The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.

Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.
 

Fewer in intensive group hit target

The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).

The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).

Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).

Rates of adverse and serious adverse events were similar between the groups.

The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.

“However, improved erosion scores were not observed in this study,” the authors noted.

The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.

They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.
 

Pegloticase not available outside United States

However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.

Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.
 

Managing gout is a long-term process

Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.

“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Dr. Baraf said.

He agreed with Dr. Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.

He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”

He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.

“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Dr. Baraf.

It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.

“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.

The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”

Dr. Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Dr. Gaffo reported no relevant financial relationships. Dr. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.

In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.

By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.

So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.

However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.

And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.

Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”

In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”

In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.

A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.

Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”

As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).

In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”

Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.

In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get. 

In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.

By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.

So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.

However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.

And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.

Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”

In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”

In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.

A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.

Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”

As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).

In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”

Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.

In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get. 

In early January, Ohio not only set a state record for COVID-19 hospitalizations—it had the fourth highest rate in the country, with 6,747 hospitalized coronavirus patients on January 10, a 40% increase over the previous 21 days. Most were unvaccinated. To help overwhelmed hospitals cope, Ohio Gov. Mike DeWine turned to the National Guard. Unfortunately, nearly half of the Ohio National Guard also were unvaccinated.

By US Department of Defense (DoD) directive, National Guard members must have a COVID-19 vaccination to be deployed on hospital missions. Thus, in COVID hotspots across the nation, governors are on the horns of a dilemma. They want and need to deploy the National Guard to give medical and nonclinical support but aren’t sure whether they will be able to or, indeed, whether they should.

So far, vaccinated teams are already on the ground in a number of states. In Indiana, where hospitalizations jumped 50% over 2 weeks in December, the National Guard sent 6-person teams, all fully vaccinated. In New Hampshire, 70 guards are being deployed to help hospitals with food service, clerical work, and other nonmedical functions. New York Governor Kathy Hochul has deployed guard members for help to ease the strain on nursing homes. Massachusetts Governor Charlie Baker has activated up to 500 guard members; some will be supporting 55 acute care hospital and 12 ambulance services. In Maine, where cases have peaked, Governor Janet Mills activated guard members to support nursing facilities and administer monoclonal antibodies. The Louisiana National Guard has administered more than 542,000 COVID-19 tests and 206,300 vaccines. As many as 1,000 Maryland Air and Army National Guardsmen are being activated to help with testing and other missions.

However, as in Ohio, other states are facing problematic scenarios. For instance, about 40% of the more than 20,000 Texas National Guard are refusing to get vaccinated, challenging the Biden Administration vaccine requirement for all military.

And a court showdown over federal vaccine mandates, started by Governor Kevin Stitt of Oklahoma and joined by the Republican governors of Wyoming, Iowa, Alaska, Nebraska, and Mississippi, came to a head in December. Last November, Stitt asked Defense Secretary Lloyd Austin to exempt Oklahoma’s National Guard from the vaccine mandate. He claimed the requirement violated the personal freedoms of many Oklahomans and could cause them to “potentially sacrifice their personal beliefs.” But in a memo to the Joint Chiefs chairmen, the service secretaries and the head of the National Guard Bureau, Austin wrote that Pentagon funds could not be used to pay for duties performed under Title 32 for members of the Guard who do not comply with the military’s vaccine requirement. (Title 32 refers to Guard operations under state orders.) Austin also said National Guard members must be vaccinated to participate in drills, training, and other duty conducted under Title 32.

Stitt, maintaining that he is commander in chief of the Oklahoma National Guard as long as it operates under Title 32 orders, put out his own memo stipulating that no Guard member was required to get vaccinated. He also ordered Brig. Gen. Thomas Mancino, newly appointed commander of the Oklahoma National Guard, to not enforce the mandate. Subsequently, Mancino issued a statement pointing out that current state law is limited in protecting troops who opt out of the shot. Moreover, if the Guard were called up under federal orders, he said, he would enforce the mandate. Training events, schools, and mobilizations were going to “eventually force you out of that safe harbor,” he wrote, “…This is reality.”

In late December, a federal judge denied Oklahoma’s motion to enjoin the mandate. The Oklahoma Attorney General’s office responded, “We will not be surprised if the President’s vaccine mandate actually reduces the nation’s military readiness instead of promoting it.”

In a press briefing, Pentagon press secretary John Kirby said, “The Secretary has the authorities he needs to require this vaccine across the force, including the National Guard. …[E]ven when they’re in a Title 32 status.” He added, “It is a lawful order for National Guardsmen to receive the COVID vaccine. It’s a lawful order, and refusing to do that, absent of an improved exemption, puts them in the same potential [position] as active-duty members who refuse the vaccine.” That could mean, for instance, loss of pay and membership in the National Guard.

A core rationale for the mandate, according to Secretary Austin, is the need for military readiness—meaning Guard members must be healthy and fit for duty. And that extends to being healthy and fit for missions like transporting at-risk patients. Ohio National Guard Adjutant General Major General John Harris Jr. said, “I would never put a soldier or airman in harm’s way without the best protection we could put on them—body armor, helmets. And this medical readiness is the exact same thing. We’re putting folks into harm’s way.” He has moved the deadline from the Pentagon’s June 30 date to March 31—a move that boosted the vaccination rate from 53% to 56% in one week.

Ohio Governor DeWine has expressed frustration that almost half of the Ohio Army National Guard personnel can’t be deployed on this mission because they’re unvaccinated. “In some of our testing places, 40 to 50% of the people are testing positive,” he said. “So this is a high-risk operation. You need to be protected. The best way for you to be protected is to get the vaccination.”

As of December 2021, according to the National Guard Bureau, the National Guard as a whole was 66% fully vaccinated. The percentages vary according to service; for instance, nearly 90% of airmen have been vaccinated, compared with only 40% of Army Guardsmen. Among the states challenging the mandate, the vaccinated rates have been moving upward: In Alaska, about 92% of the Air National Guard have been vaccinated—leaving roughly 11,000 troops who had not met the December 2 deadline. In Iowa, as of Nov. 30, 91% of Air National Guard and 80% of Army National Guard members had been vaccinated, but about 9,000 soldiers had been directed to get the vaccination or risk disciplinary action. Almost 2,200 of the more than 2,800-strong Wyoming National Guard (77%) have received at least 1 dose. Nebraska Air National Guard’s force of 1,000 was 94% fully vaccinated as of December 1. (Maj Scott Ingalsbe, public affairs officer, said, “Vaccinations are tied to individual medical readiness. They provide service members with the best protection available so they can perform missions across the globe.”).

In most states, Army National Guard members have until June 30, 2022, to comply. “Our soldiers …have until [the DoD’s deadline], and some of them are just going to wait close to the deadline,” John Goheen of the National Guard Association of the United States said in a discussion on NPR. “That’s human nature.”

Earlier this month, Texas Governor Greg Abbott told National Guard members they can ignore the Pentagon’s COVID-19 vaccine mandate: “President Biden is not your commander-in-chief.” He has also sued the Biden administration over the requirement.

In the meantime, the hospitals at breaking point must hope for the best and take as much help as they can get. 

Having specific health issues, including depressive symptoms and cardiovascular disease, as a middle-aged woman was associated with experiencing clinically important declines in health later in life, a new study finds.

The most predictive parameters of poorer health at age 65 were cardiovascular disease, clinically significant depressive symptoms, and current smoking. Osteoarthritis, lower education level, and higher body mass index (BMI) also were associated with poorer health status 10 years on, Daniel H. Solomon, MD, MPH and colleagues wrote in their observational study, which was published in JAMA Network Open.

Determining a patient’s score on a health-related quality of life measure based on these variables might be useful in clinical practice to recognize midlife patients at increased risk for later health deterioration, Dr. Solomon, of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital, Boston, said in a statement. This measure is called the Short Form 36 (SF-36), and the researchers specifically focused on the physical component summary score (PCS) of this measure. The SF-36 is similar to the Framingham 10-year coronary heart disease risk prediction score, according to Dr. Solomon, who is a professor of medicine at Harvard Medical School, also in Boston.

Based on their risk scores, women could preemptively target modifiable risk factors before they enter old age, the investigators wrote.

“Age 55-65 may be a critical decade. A person’s health and factors during this period may set them on a path for their later adult years,” Dr. Solomon said in a statement. “The good news is that a large proportion of women at midlife are very stable and will not go on to experience declines. But being able to identify women at higher risk could help lead to interventions targeted to them.”
 

Study details

The study included a cohort of 1,091 women drawn from the 3,302-participant Study of Women’s Health Across the Nation (SWAN), a racially and ethnically diverse group enrolled from six U.S. sites at or immediately before transition to menopause and followed for 10 years from age 55 to 65. The study sample, consisting of 24.6% Black, 24% Japanese or Chinese, and 51.9% White, had a median baseline age of 54.8 years and median BMI of 27 kg/m² at entry. The median baseline PCS score was 53.1 (interquartile range, 46.8-56.7).

Over 10 years, 206 (18.9%) of the women in the study experienced clinically important declines of at least 8 points in baseline characteristics at around age 55. The following were significantly associated with these declines:

• Having a higher BMI.
• Having osteoarthritis.
• Having a lower educational level.
• Being a current smoker.
• Having clinically significant depressive symptoms.
• Having cardiovascular disease.
• Having better (or higher) physical health and function score on the PCS.

The association between a higher PCS score and a greater decline might seem like an anomaly, Dr. Solomon said in an interview, but one interpretation of this finding is that women with higher or better scores at baseline have further to fall once other risk factors take effect.

With data analyzed from October 2020 to March 2021, the median 10-year change in PCS was –1.02 points, but 206 women experienced declines of 8 points or more.

Those with health declines were more likely to be Black and less likely to be Japanese. They were also more likely to have other comorbidities such as diabetes, hypertension, and osteoporosis, and to report less physical activity.
 

Scoring system should not replace individualized evaluation, outside expert said

Commenting on the findings, Margaret J. Nachtigall, MD, a clinical associate professor in the department of obstetrics and gynecology at New York University Langone Health, cautioned that a generalized scoring system should not replace individualized evaluation of women at midlife.

“I assess women around age 55 on a daily basis for health risk factors going forward. And while a number such as BMI can be helpful, I worry that reliance on a score could miss treating the individual,” Dr. Nachtigall said an interview. For instance, one woman might have a high BMI owing to greater muscle mass, which is heavy, while another may have a lower BMI but more fat-related weight, as well as exacerbating conditions such as hypertension that would elevate her risk. “You have to make the calculation for each person.”

Dr. Nachtigall, who was not involved in the SWAN analysis, noted, however, that a big-data scoring system might be a useful adjunct to individual patient evaluation in that “it would make physicians look at all these many risk factors to identify those prone to decline.”
 

Study includes racially diverse population

According to the authors, while other studies have identified similar and other risk factors such as poor sleep, most have not included such a racially diverse population and have focused on women already in their senior years when the window of opportunity may already have closed.

“As a clinician and epidemiologist, I often think about the window of opportunity at midlife, when people are vital, engaged, and resilient,” said Dr. Solomon in the statement. “If we can identify risk factors and determine who is at risk, we may be able to find interventions that can stave off health declines and help put people on a better health trajectory.”

Eric M. Ascher, DO, who practices family medicine at Lenox Hill Hospital in New York and was not involved in the SWAN research, agreed with Dr. Solomon.

“Doctors who treat chronic conditions often meet patients when they are already suffering from a medical problem,” he said in an interview. “It is key to decrease your risk factors before it is too late.”

Dr. Ascher added that many primary care providers already rely heavily on scoring systems when determining level of risk and type of intervention. “Any additional risk factor-scoring systems that are easy to implement and will prevent chronic diseases would be something providers would want to use with their patients.”

Detailed analyses of larger at-risk populations are needed to validate these risk factors and identify others, the authors said.

SWAN is supported by the National Institute on Aging, the National Institute of Nursing Research, and the National Institutes of Heath’s Office of Research on Women’s Health. Dr. Solomon reported financial ties to Amgen, AbbVie and Moderna, UpToDate, and Arthritis & Rheumatology; as well as serving on the board of directors for the Childhood Arthritis and Rheumatology Research Alliance and an advisory committee for the Food and Drug Administration outside of this work. Dr. Nachtigall and Dr. Ascher disclosed no conflicts of interest with regard to their comments.

Having specific health issues, including depressive symptoms and cardiovascular disease, as a middle-aged woman was associated with experiencing clinically important declines in health later in life, a new study finds.

The most predictive parameters of poorer health at age 65 were cardiovascular disease, clinically significant depressive symptoms, and current smoking. Osteoarthritis, lower education level, and higher body mass index (BMI) also were associated with poorer health status 10 years on, Daniel H. Solomon, MD, MPH and colleagues wrote in their observational study, which was published in JAMA Network Open.

Determining a patient’s score on a health-related quality of life measure based on these variables might be useful in clinical practice to recognize midlife patients at increased risk for later health deterioration, Dr. Solomon, of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital, Boston, said in a statement. This measure is called the Short Form 36 (SF-36), and the researchers specifically focused on the physical component summary score (PCS) of this measure. The SF-36 is similar to the Framingham 10-year coronary heart disease risk prediction score, according to Dr. Solomon, who is a professor of medicine at Harvard Medical School, also in Boston.

Based on their risk scores, women could preemptively target modifiable risk factors before they enter old age, the investigators wrote.

“Age 55-65 may be a critical decade. A person’s health and factors during this period may set them on a path for their later adult years,” Dr. Solomon said in a statement. “The good news is that a large proportion of women at midlife are very stable and will not go on to experience declines. But being able to identify women at higher risk could help lead to interventions targeted to them.”
 

Study details

The study included a cohort of 1,091 women drawn from the 3,302-participant Study of Women’s Health Across the Nation (SWAN), a racially and ethnically diverse group enrolled from six U.S. sites at or immediately before transition to menopause and followed for 10 years from age 55 to 65. The study sample, consisting of 24.6% Black, 24% Japanese or Chinese, and 51.9% White, had a median baseline age of 54.8 years and median BMI of 27 kg/m² at entry. The median baseline PCS score was 53.1 (interquartile range, 46.8-56.7).

Over 10 years, 206 (18.9%) of the women in the study experienced clinically important declines of at least 8 points in baseline characteristics at around age 55. The following were significantly associated with these declines:

• Having a higher BMI.
• Having osteoarthritis.
• Having a lower educational level.
• Being a current smoker.
• Having clinically significant depressive symptoms.
• Having cardiovascular disease.
• Having better (or higher) physical health and function score on the PCS.

The association between a higher PCS score and a greater decline might seem like an anomaly, Dr. Solomon said in an interview, but one interpretation of this finding is that women with higher or better scores at baseline have further to fall once other risk factors take effect.

With data analyzed from October 2020 to March 2021, the median 10-year change in PCS was –1.02 points, but 206 women experienced declines of 8 points or more.

Those with health declines were more likely to be Black and less likely to be Japanese. They were also more likely to have other comorbidities such as diabetes, hypertension, and osteoporosis, and to report less physical activity.
 

Scoring system should not replace individualized evaluation, outside expert said

Commenting on the findings, Margaret J. Nachtigall, MD, a clinical associate professor in the department of obstetrics and gynecology at New York University Langone Health, cautioned that a generalized scoring system should not replace individualized evaluation of women at midlife.

“I assess women around age 55 on a daily basis for health risk factors going forward. And while a number such as BMI can be helpful, I worry that reliance on a score could miss treating the individual,” Dr. Nachtigall said an interview. For instance, one woman might have a high BMI owing to greater muscle mass, which is heavy, while another may have a lower BMI but more fat-related weight, as well as exacerbating conditions such as hypertension that would elevate her risk. “You have to make the calculation for each person.”

Dr. Nachtigall, who was not involved in the SWAN analysis, noted, however, that a big-data scoring system might be a useful adjunct to individual patient evaluation in that “it would make physicians look at all these many risk factors to identify those prone to decline.”
 

Study includes racially diverse population

According to the authors, while other studies have identified similar and other risk factors such as poor sleep, most have not included such a racially diverse population and have focused on women already in their senior years when the window of opportunity may already have closed.

“As a clinician and epidemiologist, I often think about the window of opportunity at midlife, when people are vital, engaged, and resilient,” said Dr. Solomon in the statement. “If we can identify risk factors and determine who is at risk, we may be able to find interventions that can stave off health declines and help put people on a better health trajectory.”

Eric M. Ascher, DO, who practices family medicine at Lenox Hill Hospital in New York and was not involved in the SWAN research, agreed with Dr. Solomon.

“Doctors who treat chronic conditions often meet patients when they are already suffering from a medical problem,” he said in an interview. “It is key to decrease your risk factors before it is too late.”

Dr. Ascher added that many primary care providers already rely heavily on scoring systems when determining level of risk and type of intervention. “Any additional risk factor-scoring systems that are easy to implement and will prevent chronic diseases would be something providers would want to use with their patients.”

Detailed analyses of larger at-risk populations are needed to validate these risk factors and identify others, the authors said.

SWAN is supported by the National Institute on Aging, the National Institute of Nursing Research, and the National Institutes of Heath’s Office of Research on Women’s Health. Dr. Solomon reported financial ties to Amgen, AbbVie and Moderna, UpToDate, and Arthritis & Rheumatology; as well as serving on the board of directors for the Childhood Arthritis and Rheumatology Research Alliance and an advisory committee for the Food and Drug Administration outside of this work. Dr. Nachtigall and Dr. Ascher disclosed no conflicts of interest with regard to their comments.

Having specific health issues, including depressive symptoms and cardiovascular disease, as a middle-aged woman was associated with experiencing clinically important declines in health later in life, a new study finds.

The most predictive parameters of poorer health at age 65 were cardiovascular disease, clinically significant depressive symptoms, and current smoking. Osteoarthritis, lower education level, and higher body mass index (BMI) also were associated with poorer health status 10 years on, Daniel H. Solomon, MD, MPH and colleagues wrote in their observational study, which was published in JAMA Network Open.

Determining a patient’s score on a health-related quality of life measure based on these variables might be useful in clinical practice to recognize midlife patients at increased risk for later health deterioration, Dr. Solomon, of the division of rheumatology, inflammation, and immunity at Brigham and Women’s Hospital, Boston, said in a statement. This measure is called the Short Form 36 (SF-36), and the researchers specifically focused on the physical component summary score (PCS) of this measure. The SF-36 is similar to the Framingham 10-year coronary heart disease risk prediction score, according to Dr. Solomon, who is a professor of medicine at Harvard Medical School, also in Boston.

Based on their risk scores, women could preemptively target modifiable risk factors before they enter old age, the investigators wrote.

“Age 55-65 may be a critical decade. A person’s health and factors during this period may set them on a path for their later adult years,” Dr. Solomon said in a statement. “The good news is that a large proportion of women at midlife are very stable and will not go on to experience declines. But being able to identify women at higher risk could help lead to interventions targeted to them.”
 

Study details

The study included a cohort of 1,091 women drawn from the 3,302-participant Study of Women’s Health Across the Nation (SWAN), a racially and ethnically diverse group enrolled from six U.S. sites at or immediately before transition to menopause and followed for 10 years from age 55 to 65. The study sample, consisting of 24.6% Black, 24% Japanese or Chinese, and 51.9% White, had a median baseline age of 54.8 years and median BMI of 27 kg/m² at entry. The median baseline PCS score was 53.1 (interquartile range, 46.8-56.7).

Over 10 years, 206 (18.9%) of the women in the study experienced clinically important declines of at least 8 points in baseline characteristics at around age 55. The following were significantly associated with these declines:

• Having a higher BMI.
• Having osteoarthritis.
• Having a lower educational level.
• Being a current smoker.
• Having clinically significant depressive symptoms.
• Having cardiovascular disease.
• Having better (or higher) physical health and function score on the PCS.

The association between a higher PCS score and a greater decline might seem like an anomaly, Dr. Solomon said in an interview, but one interpretation of this finding is that women with higher or better scores at baseline have further to fall once other risk factors take effect.

With data analyzed from October 2020 to March 2021, the median 10-year change in PCS was –1.02 points, but 206 women experienced declines of 8 points or more.

Those with health declines were more likely to be Black and less likely to be Japanese. They were also more likely to have other comorbidities such as diabetes, hypertension, and osteoporosis, and to report less physical activity.
 

Scoring system should not replace individualized evaluation, outside expert said

Commenting on the findings, Margaret J. Nachtigall, MD, a clinical associate professor in the department of obstetrics and gynecology at New York University Langone Health, cautioned that a generalized scoring system should not replace individualized evaluation of women at midlife.

“I assess women around age 55 on a daily basis for health risk factors going forward. And while a number such as BMI can be helpful, I worry that reliance on a score could miss treating the individual,” Dr. Nachtigall said an interview. For instance, one woman might have a high BMI owing to greater muscle mass, which is heavy, while another may have a lower BMI but more fat-related weight, as well as exacerbating conditions such as hypertension that would elevate her risk. “You have to make the calculation for each person.”

Dr. Nachtigall, who was not involved in the SWAN analysis, noted, however, that a big-data scoring system might be a useful adjunct to individual patient evaluation in that “it would make physicians look at all these many risk factors to identify those prone to decline.”
 

Study includes racially diverse population

According to the authors, while other studies have identified similar and other risk factors such as poor sleep, most have not included such a racially diverse population and have focused on women already in their senior years when the window of opportunity may already have closed.

“As a clinician and epidemiologist, I often think about the window of opportunity at midlife, when people are vital, engaged, and resilient,” said Dr. Solomon in the statement. “If we can identify risk factors and determine who is at risk, we may be able to find interventions that can stave off health declines and help put people on a better health trajectory.”

Eric M. Ascher, DO, who practices family medicine at Lenox Hill Hospital in New York and was not involved in the SWAN research, agreed with Dr. Solomon.

“Doctors who treat chronic conditions often meet patients when they are already suffering from a medical problem,” he said in an interview. “It is key to decrease your risk factors before it is too late.”

Dr. Ascher added that many primary care providers already rely heavily on scoring systems when determining level of risk and type of intervention. “Any additional risk factor-scoring systems that are easy to implement and will prevent chronic diseases would be something providers would want to use with their patients.”

Detailed analyses of larger at-risk populations are needed to validate these risk factors and identify others, the authors said.

SWAN is supported by the National Institute on Aging, the National Institute of Nursing Research, and the National Institutes of Heath’s Office of Research on Women’s Health. Dr. Solomon reported financial ties to Amgen, AbbVie and Moderna, UpToDate, and Arthritis & Rheumatology; as well as serving on the board of directors for the Childhood Arthritis and Rheumatology Research Alliance and an advisory committee for the Food and Drug Administration outside of this work. Dr. Nachtigall and Dr. Ascher disclosed no conflicts of interest with regard to their comments.

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

Inpatient and outpatient treatments of transient ischemic attack (TIA) or minor ischemic stroke (mIS) yield comparable safety outcomes, new research suggests. In a meta-analysis of more than 200,000 patients with TIA or mIS, risk for subsequent stroke within 90 days was 2.1% for those treated in a TIA clinic versus 2.8% for patients treated in inpatient settings, which was not significantly different. The risk for patients treated in an emergency department was higher, at 3.5%.

“The message is that if you do the correct risk stratification and then triage patients based on their risk profile, you can safely discharge and have a timely follow-up for the patients who have low risk for a subsequent event,” said coinvestigator Ramin Zand, MD, vascular neurologist and stroke attending physician at Geisinger Health System, Danville, Pennsylvania.

The findings were published online Jan. 5 in JAMA Network Open.
 

Higher risk in EDs

There is currently no consensus on the care protocol for patients with TIA or mIS, and the rate at which these patients are hospitalized varies by region, hospital, and practitioner, the investigators noted.

Previous studies have indicated that outpatient management of certain individuals with TIA can be safe and cost-effective.

The current researchers searched for retrospective and prospective studies of adult patients that provided information about ischemic stroke after TIA or mIS. Studies that used time- and tissue-based definitions of TIA were included, as well as studies that used various definitions of mIS.

The investigators examined care provided at TIA clinics, inpatient settings (such as medical-surgical units, stroke units, or observation units), EDs, and unspecified settings. Their main aim was to compare outcomes between TIA clinics and inpatient settings.

In all, 226,683 patients (recruited between 1981 and 2018) from 71 studies were included in the meta-analysis. The studies examined 101 cohorts, 24 of which were studied prospectively. Among the 5,636 patients who received care in TIA clinics, the mean age was 65.7 years, and 50.8% of this group were men. Among the 130,139 inpatients, the mean age was 78.3 years, and 61.6% of the group were women.

Results showed no significant difference in risk for subsequent stroke between patients treated in the inpatient and outpatient settings.

Among patients treated in a TIA clinic, risk for subsequent stroke following a TIA or mIS was 0.3% within 2 days, 1.0% within 7 days, 1.3% within 30 days, and 2.1% within 90 days. Among those treated as inpatients, risk for subsequent stroke was 0.5% within 2 days, 1.2% within 7 days, 1.6% within 30 days, and 2.8% within 90 days.

Risk for subsequent stroke was higher among patients treated in the ED and in unspecified settings. At the EDs, the risk was 1.9% within 2 days, 3.4% within 7 days, 3.5% within 30 days, and 3.5% within 90 days. Among those treated in unspecified settings, the risk was 2.2% within 2 days, 3.4% within 7 days, 4.2% within 30 days, and 6.0% within 90 days.

Patients treated in the ED also had a significantly higher risk for subsequent stroke at 2 and 7 days, compared with those treated in inpatient settings and a significantly higher risk for subsequent stroke at 2, 7, and 90 days, compared with those treated in TIA clinics.
 

‘Most comprehensive look’

“This is the most comprehensive look at all the studies to try and answer this research question,” said Dr. Zand. The results were similar to what was expected, he added.

The infrastructure and resources differed among the sites at which the various studies were conducted, and the investigators adjusted for these differences as much as possible, Dr. Zand noted. A certain amount of selection bias may remain, but it does not affect the overall conclusion, he added.

“Timely outpatient care among low-risk TIA patients is both feasible and safe,” he said.

Dr. Zand noted that the findings have implications not only for patient management but also for the management of the health system. “It’s not feasible nor desirable to admit all the TIA patients, especially with the lessons that we learned from COVID, the burden on the health systems, and the fact that many hospitals are operating at full capacity right now,” he said.

The recommendation is to hospitalize high-risk patients and provide outpatient evaluation and workup to low-risk patients, he added. “This is exactly what we saw in this study,” Dr. Zand said.
 

Selection bias?

Commenting on the research, Louis R. Caplan, MD, professor of neurology at Harvard Medical School, Boston, noted that evaluation of patients with TIA or mIS “can be done very well as an outpatient” if clinicians have experienced personnel, the outpatient facilities to do the studies necessary, and criteria in place for deciding who to admit or not admit.

However, the decision on whether to choose an inpatient or outpatient approach for a particular patient is complicated, said Dr. Caplan, who was not involved with the research.

Clinicians must consider factors such as whether the patient is mobile, has a car, or has a significant other. The patient’s symptoms and past illnesses also influence the decision, he added.

Dr. Caplan noted that in the meta-analysis, far fewer patients were seen in the TIA clinics than were seen in the inpatient setting. In addition, none of the studies used uniform criteria to determine which patients should undergo workup as outpatients and which as inpatients. “There was a lot of selection bias that may have had nothing to do with how sick the person was,” Dr. Caplan said.

In addition, few hospitals in the United States have an outpatient TIA clinic, he noted. Most of the studies of TIA clinics that the researchers examined were conducted in Europe. “It’s easier to do [that] in Europe because of their socialized medicine,” said Dr. Caplan.

But TIA clinics should be more widespread in the U.S., he added. “Insurance companies should be willing to pay for comparable facilities, inpatient and outpatient,” he said.

The study was conducted without external funding. Dr. Zand reported no relevant financial relationships. Dr. Caplan was an investigator for TIAregistry.org, which analyzed the outcomes of treatment in TIA clinics in Europe.

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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

The risk of myocarditis after immunization with mRNA-based vaccines against SARS-CoV-2 raised concerns when it came to light in early 2021. But as report after report showed such cases to be rare and usually mild and self-limited, focus has turned to the “how and why.”  

The mechanism linking the BNT162b2 (Pfizer-BioNTech) and especially mRNA-1273 (Moderna) vaccines to the occurrence of myocarditis is unclear for now, but one potential driver may be tied to a peculiarity that became apparent early: It occurs overwhelmingly in younger males, from 16 to perhaps 40 or 50 years of age. Excess risk has not been consistently seen among women, girls, and older men.

peterschreiber_media/iStock/Getty Images

That observation has led to speculation that higher testosterone levels in adolescent boys and young men may somehow promote the adverse vaccine effect, whereas greater levels of estrogen among girls and women in the same age range may be cardioprotective.
 

Unlikely, brief, and ‘benign’

“Most of the myocarditis is benign, by which I mean that maybe the patients are admitted due to chest pain, but without reduction in ventricular function,” Enrico Ammirati, MD, PhD, a myocarditis expert at De Gasperis Cardio Center and Transplant Center, Niguarda Hospital, Milan, said in an interview.

In a Nov. 14 address on this topic at the annual scientific sessions of the American Heart Association, Dror Mevorach, MD, described the typical case presentation as “mild” and one that clears in fairly short order based on resolution of “clinical symptoms, inflammatory markers and troponin decline, EKG normalization, echo normalization, and a relatively short length of hospital stay.”

Dr. Mevorach, of Hadassah Hebrew University Medical Center, Jerusalem, subsequently published the findings in a report in the New England Journal of Medicine that described 136 confirmed myocarditis cases among more than 5 million people in Israel immunized with the Pfizer-BioNTech vaccine. Myocarditis was considered “mild” in 129 cases, or 95%.

And the risk is tiny, compared with myocarditis from infection by SARS-CoV-2, not to mention the possibility of nasty clinical COVID-19 complications such as pneumonia and pulmonary embolism, Dr. Mevorach observed.

Many other reports agree that the incidence is minimal, especially given the rewards of vaccination. In a separate NEJM publication in September 2021 – from Noam Barda, MD, Clalit (Israel) Research Institute, and colleagues on 1.7 million people in that country, about half unvaccinated and half given the Pfizer-BioNTech vaccine – there were an estimated 2.7 cases of  myocarditis per 100,000 vaccinated persons. There were also 11 cases of myocarditis per 100,000 persons who were positive for SARS-CoV-2 infection.

And in a recent case series of vaccinated people aged 16 or older, the myocarditis rate after a first or second Pfizer-BioNTech or Moderna injection was estimated at 1 or fewer per 100,000. The corresponding estimate was 4 such cases per 100,000 after a positive SARS-CoV-2 test among the same population, notes a report published Dec.14, 2021, in Nature Medicine.

In general, “the risk of any kind of cardiac injury is vastly lower with a vaccine than it is with the actual viral infection,” Leslie T. Cooper Jr., MD, a myocarditis expert and clinical trialist at the Mayo Clinic, Jacksonville, Fla., said in an interview. With the mRNA-based vaccines, “we do not have any conceivable danger signal that would outweigh the benefit of vaccination.”
 

Males of a certain age

Evidence that such myocarditis predominates in young adult men and adolescent boys, especially following a second vaccine dose, is remarkably consistent.

The risk was elevated only among mRNA-based vaccine recipients who were younger than 40 in the recent Nature Medicine analysis. Among that group, estimates after a second dose numbered fewer than 1 case per 100,000 for Pfizer-BioNTech and 1.5 per 100,000 for Moderna.

In a third analysis from Israel – also in NEJM, from Guy Witberg, MD, Rabin Medical Center, Petah Tikva, and colleagues, based on 2.5 million people aged 16 and older with at least one Pfizer-BioNTech injection – 2.1 cases per 100,000 were estimated overall, but the number rose to 10.7 per 100,000 among those aged 16-29 years.

In Dr. Mevorach’s NEJM report, estimates after a second Pfizer-BioNTech vaccine dose were 1 per 26,000 males versus 1 in 218,000 females, compared with 1 myocarditis case in 10,857 persons among “the general unvaccinated population.”

Most recipients of a first vaccine dose were younger than 50, and 16- to 29-year-olds accounted for most who completed two doses, noted Dr. Mevorach. Younger males bore the brunt of any myocarditis: the estimated prevalence after a second dose among males aged 16-19 was 1 per 6,637, compared with 1 per 99,853 females in the same age range, the group reported.

In the BMJ report, based on about 5 million people 12 years of age or older in Denmark, the estimated rates of myocarditis or pericarditis associated with Moderna immunization were 2 per 100,000 among women but 6.3 per 100,000 for men. The incidence and sex difference was much lower among those getting the Pfizer-BioNTech vaccine: 1.3 per 100,000 and 1.5 per 100,000 in women and men, respectively.
 

Sex hormones may be key

The predominance of vaccine-associated myocarditis among adolescent and young adult males is probably more about the myocarditis itself than the vaccines, observed Biykem Bozkurt, MD, PhD, who has been studying COVID-related myocarditis at Baylor College of Medicine, Houston.

Male sex historically is associated in both epidemiologic studies and experimental models with a greater propensity for most any form of myocarditis, Dr. Bozkurt said in an interview. Given that males aged 16-19 or so appear to be at highest risk of myocarditis as a complication of SARS-CoV-2 vaccination, the mechanism may well be related to sex hormones.  

“Therefore, testosterone is implicated as a player in their higher risk of inflammation and injury and lack of adaptive response in terms of healing, and in terms of prevention of injury,” Dr. Bozkurt said. For its part, estrogen inhibits proinflammatory processes and, in particular, “blunts cell-mediated immune responses.”

“We don’t know the mechanism, but a theory that attributes a protective role to estrogen, or a risk associated with testosterone, is reasonable. It makes sense, at least based on epidemiological data,” Dr. Ammirati agreed. Still, “we do not have any direct evidence in human beings.”

Sex-associated differences in experimental myocarditis have been reported in the journals for at least 70 years, but “the testosterone literature and the estrogen literature have not been evaluated in detail in vaccine-associated myocarditis,” Dr. Cooper said.

Most myocarditis in the laboratory is viral, Dr. Cooper observed, and “the links between testosterone, viruses, and inflammation have been pretty well worked out, I would say, if you’re a mouse. If you’re a human, I think it’s still a bit uncertain.”

Were it to apply in humans, greater testosterone levels might independently promote myocarditis, “and if estrogen is cardioprotective, it would be another mechanism,” Dr. Cooper said. “That would translate to slight male predominance in most kinds of myocarditis.”

In males, compared with females, “the heart can be more vulnerable to events such as arrhythmias or to immune-mediated phenomena. So, probably there is also higher vulnerability to myocarditis in men,” Dr. Ammirati noted.

Male predominance in vaccine-related myocarditis is provocative, so it’s worth considering whether testosterone is part of the mechanism as well as the possibility of estrogen cardioprotection, Dr. Ammirati said. But given limitations of the animal models, “we don’t really have robust data to support any part of that.”

Although myocarditis is in some way immune mediated, “and hormones can modulate the response,” the mechanism has to be more than just sex hormones, he said. “They probably cannot explain the specificity for the heart. It’s not a systemic response, it’s an organ-specific response.”
 

Modulation of immune responses

Details about the immune processes underlying mRNA-vaccine myocarditis, hormone modulated or not, have been elusive. The complication doesn’t resemble serum sickness, nor does it seem to be a reaction to infection by other cardiotropic viruses, such as coxsackie virus B, a cause of viral myocarditis, Dr. Bozkurt said. The latter had been a compelling possibility because such hypersensitivity to smallpox vaccination is well recognized.

“We don’t know the mechanism, that’s the short answer. But there are many hypotheses,” she said. One candidate widely proposed in the literature: autoantibodies driven by molecular mimicry between the SARS-CoV-2 spike protein targeted by the mRNA vaccines and a structurally similar myocardial protein, possibly alpha-myosin, noted Dr. Bozkurt and colleagues in a recent publication.

But elevations in specific “antiheart antibodies” have not been documented in recipients of the two mRNA-based vaccines, said Dr. Cooper. “So, I would say that – although molecular mimicry is a well-established mechanism of, for example, rheumatic carditis after a streptococcal A infection – that has not been demonstrated yet for COVID-19 mRNA vaccination–related myocarditis.”

“We probably won’t know, ever, with a huge level of certainty, the exact mechanisms,” Dr. Cooper added. There is no animal model for vaccine-induced myocarditis, and “We’re still talking very, very small numbers of patients. The vast majority of them recover,” and so don’t generally provide mechanistic clues.  
 

Prospects for younger children

Vaccination against SARS-CoV-2 has now been authorized by the Centers for Disease Control and Prevention for kids as young as 5-11 years, using the Pfizer-BioNTech vaccine. Experience so far suggests the immunization is safe in that age group with negligible risk of myocarditis or other complications. But with prospects of possible authorization in children younger than 5, should myocarditis be a concern for them?

Probably not, if the complication is driven primarily by sex hormones, Dr. Cooper proposed. “One would predict that before puberty you would have a lower – much, much lower – rate of myocarditis in males than you would in the 16- to 19-year-old range, and that it would be roughly equal to females.” Dr. Ammirati and Dr. Bozkurt largely agreed.

It remains to be seen whether the vaccine-related myocarditis risk applies to children younger than 12, “but I doubt it. I think it’s going to be puberty-related,” Dr. Bozkurt said. Still, “I don’t want to hypothesize without data.”

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