COVID-19 infection was associated with accelerated vascular aging that persisted for months following illness, particularly among women, according to a large international study. Researchers reported that patients who recovered from COVID-19 had stiffer arteries compared with those who were never infected.
More specifically, COVID-19 positive patients had higher pulse wave velocity (PWV) values compared with controls. This increase was present across groups regardless of hospitalization. The researchers found that magnitude of COVID-19-induced accelerated vascular aging in women with mild COVID and women who were hospitalized in general wards was around +0.5 m/s compared with COVID negative women, which roughly corresponded to +5 years of vascular aging and +3% increased risk for cardiovascular events. In COVID-positive women who were hospitalized in the ICU, PWV elevation corresponded to about +7.5 years of vascular aging and +5.5% risk for CV events. These increases are clinically relevant, they noted.
In contrast, men did not show statistically significant differences compared with controls. Women who reported persistent symptoms such as fatigue, dyspnea, or muscle pain had higher values than women who fully recovered. No such differences were found in men. Vaccination status also influenced outcomes in women: Vaccinated women had lower stiffness values compared with unvaccinated women. However, among men, vaccination was not associated with these differences.
At 1-year follow-up, PWV values remained stable or improved among COVID-19 positive patients, while they worsened in controls. In seven participants who were initially negative but later contracted COVID-19, PWV increased following infection.
The study included 2,390 patients across 34 centers in 16 countries. Participants were divided into four groups: COVID-19 negative controls, COVID-19 positive patients who were not hospitalized, COVID-19 positive hospitalized patients, and patients who were treated for COVID-19 in intensive care units. Carotid-femoral PWV, a standard measure of arterial stiffness and vascular aging, was the primary outcome. Nonhospitalized patients were a median age of 45 years, while hospitalized and intensive care patients were a median age of 58 years. Diabetes and hypertension were more prevalent in hospitalized patients compared with nonhospitalized patients and controls.
Lead author Rosa Maria Bruno, MD, PhD, of INSERM U970, Paris Cardiovascular Research Centre, Université Paris Cité, and Hôpital Européen Georges Pompidou, in Paris, France, noted with fellow investigators that men were more susceptible to severe acute forms of COVID-19 that required hospitalization or intensive care, while women were more likely to experience long COVID and were more common among nonhospitalized groups. They cautioned that hospitalization status might not be a reliable marker of severity because CARTESIAN participants were recruited during the early pandemic, when hospitals were unable to admit all patients who might have required care.
"Since severe systemic infections, such as hospitalized pneumonia and sepsis are associated with increased long-term risk of CV events, the greater impact of COVID-19 on PWV seen in ICU patients may not be specific to COVID-19," the researchers observed, and they suggested areas of future study including the effects of vaccinations, reinfections, and new COVID variants.
They also acknowledged several other limitations: Recruitment occurred mainly in the early pandemic prior to widespread vaccination, which limited applicability to later phases; the researchers were not able to determine pre-existing vascular aging; controls may not be representative of the general population because of difficulties recruiting during the pandemic and inability to adequately match to the hospitalized group; patients who experienced asymptomatic or mild COVID may have been included in the COVID negative group because of lack of systematic serology testing; and men with severe disease had higher mortality, which may have affected comparisons. Residual confounding is especially important to their vaccination results, they wrote, "which should be interpreted with caution due to potential confounding by indication."
The authors reported no conflicts of interest.
Source: European Heart Journal
