SARS-CoV-2 infection is linked with early vascular aging in the long term, especially in women, according to a recent study in the European Heart Journal.
In the multicenter CARTESIAN study, researchers found all individuals with COVID, including those with mild cases, had stiffer arteries, as shown by increased carotid-femoral pulse wave velocity, than did those who had not been infected, according to Rosa Maria Bruno, MD, PhD, professor at Paris Cardiovascular Research Centre-PARCC, Paris, France, who led the study.
“You are as old as your arteries, meaning that your blood vessels can be older than your chronological age,” increasing the risk for heart disease, Bruno said.
For the study, Bruno and colleagues categorized 2390 individuals (mean age, 50 years; 49.2% women) from 16 countries into four groups: those who never had COVID, those who had recent COVID but were not hospitalized, those hospitalized for COVID in a general ward, and those hospitalized for COVID in an ICU. They assessed pulse wave velocity, which served as the main outcome, at 6 and 12 months after SARS-CoV-2 infection.
Data showed pulse wave velocity was 0.41 m/s higher for those with COVID who were not hospitalized, 0.37 m/s higher for those with COVID who were hospitalized in general wards, and 0.4 m/s higher for those with COVID who were hospitalized in ICUs.
The average increase in pulse wave velocity in women who had mild COVID was 0.55 m/s, 0.60 m/s in women hospitalized with COVID, and 1.09 m/s for women treated in the ICU, according to Bruno.
“The effect was much greater in women than in men and in people who experienced the persistent symptoms of long COVID, such as shortness of breath and fatigue,” she said. “This is clinically relevant since it is equivalent to aging around 5 years, with a 3% increased risk for cardiovascular disease in a 60-year-old woman.”
The researchers found ongoing symptoms of infection were associated with higher pulse wave velocity among women with COVID, regardless of disease severity or cardiovascular confounders, such as age, BMI, and smoking.
After 12 months, pulse wave velocity increased in individuals who did not have COVID but remained unchanged or improved in those who recovered from COVID.
Potential Clinical Implications
Small sample sizes, lack of stratification by disease severity, and lack of sex-specific data hampered previous studies on the association between pulse wave velocity and COVID, according to the authors of an editorial accompanying the journal article.
“Importantly, the [CARTESIAN] study population was not restricted to individuals who met formal criteria for postacute COVID-19 syndrome and therefore included both asymptomatic and symptomatic survivors,” they wrote.
The study underscores the importance of sex in the understanding of vascular biology and response to various diseases, in this case postacute COVID, according to Behnood Bikdeli, MD, MS, of the Division of Cardiovascular Medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston, and an author of the editorial.
“Clinicians and patients should remain cognizant not only in addressing short-term complications, such as pneumonia or acute blood clots, but also long-term consequences, as assessed by markers of vascular change, such as aging,” he told Medscape Medical News. “A somewhat reassuring finding is that some features of vascular abnormalities were partially reversible over time. This differs from the traditional assessment of vascular aging.”
Clinicians can identify people with accelerated vascular aging and can help them reduce the risk for heart attacks and strokes in the long term, according to Bruno.
“Vascular aging is easy to measure and can be stopped with widely available treatments, such as lifestyle changes, lowering blood pressure, and taking cholesterol-lowering drugs,” she said.
Exploring Possible Explanations
In his Substack, Ground Truths, Eric Topol, MD, chair of the Department of Translational Medicine at Scripps Research Translational Institute in San Diego, noted the risk for long COVID is greatly increased in women. Having two copies of the X chromosome, as well as hormonal factors, such as estrogen and progesterone, has been associated with the immune system and propensity to inflammation, which may explain this increased risk, according to Topol.
“About 80% of autoimmune diseases occur in women,” Topol wrote. “It is possible that there’s more propensity for endothelial inflammation after COVID in women compared with men, which sets up more chance of stiffness, fibrosis, and features of early vascular aging. Another factor acknowledged by the authors [of the study] is that there is less survivorship among men, a bias that could have contributed to the marked difference by sex.”
Bruno reported honoraria for lectures or advisory board service (unrelated to the topic) from Medtronic, Servier, LXO, and El Kendi Pharmaceutical. Bikdeli reported having no financial conflicts of interest relevant to this study.
Martta Kelly is a medical journalist who lives in the New York metropolitan area.