Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study, 2025, Bruno

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Journal Article

Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study

Rosa Maria Bruno , Smriti Badhwar , Leila Abid , Mohsen Agharazii , Fabio Anastasio , Jeremy Bellien , Otto Burghuber , Luca Faconti , Jan Filipovsky , Lorenzo Ghiadoni , Cristina Giannattasio , Bernhard Hametner , Alun D Hughes , Ana Jeroncic , Ignatios Ikonomidis , Mai Tone Lonnebakken , Alessandro Maloberti , Christopher C Mayer , Maria Lorenza Muiesan , Anna Paini , Andrie Panayiotou , Chloe Park , Chakravarthi Rajkumar , Carlos Ramos Becerra , Bart Spronck , Dimitrios Terentes-Printzios , Yesim Tuncok , Thomas Weber , Pierre Boutouyrie , the CARTESIAN Investigators
Author Notes
European Heart Journal, ehaf430, https://doi.org/10.1093/eurheartj/ehaf430
Published:

17 August 2025
Article history


Abstract​

Background and Aims

Increasing evidence suggests that COVID-19 survivors experience long-term cardiovascular complications possibly through development of vascular damage. The study aimed to investigate whether accelerated vascular ageing occurs after COVID-19 infection, and if so, identify its determinants.

Methods

This prospective, multicentric, cohort study, included 34 centres in 16 countries worldwide, in 4 groups of participants—COVID-19-negative controls (ⅰ) and three groups of individuals with recent (6 ± 3 months) exposure to SARS-CoV-2: not hospitalized (ⅱ), hospitalized in general wards (ⅲ), and hospitalized in intensive care units (ⅳ). The main outcome was carotid-femoral pulse wave velocity (PWV), an established biomarker of large artery stiffness.

Results

2390 individuals (age 50 ± 15 years, 49.2% women) were recruited. After adjustment for confounders, all COVID-19-positive groups showed higher PWV (+0.41, +0.37, and +0.40 m/s for groups 2–4, P < .001, P = .001 and P = .003) vs. controls [PWV 7.53 (7.09; 7.97) m/s adjusted mean (95% CI)]. In sex-stratified analyses, PWV differences were significant in women [PWV (+0.55, +0.60, and +1.09 m/s for groups 2–4, P < .001 for all)], but not in men. Among COVID-19 positive women, persistent symptoms were associated with higher PWV, regardless of disease severity and cardiovascular confounders [adjusted PWV 7.52 (95% CI 7.09; 7.96) vs. 7.13 (95% CI 6.67; 7.59) m/s, P < .001]. A stable or improved PWV after 12 months was found in the COVID+ groups, whereas a progression was observed in the COVID− group.

Conclusions

COVID-19 is associated with early vascular ageing in the long term, especially in women.

COVID-19 effects on ARTErial StIffness and vascular AgeiNg: the CARTESIAN study. CI, COnfidence Intervals; COVID, Corona VIrus Disease; EVA, early vascular ageing; ICU, Intensive Care Unit; PWV, pulse wave velocity; SARS-COV2, Severe acute respiratory syndromecoronavirus 2.

Structured Graphical Abstract
COVID-19 effects on ARTErial StIffness and vascular AgeiNg: the CARTESIAN study. CI, COnfidence Intervals; COVID, Corona VIrus Disease; EVA, early vascular ageing; ICU, Intensive Care Unit; PWV, pulse wave velocity; SARS-COV2, Severe acute respiratory syndromecoronavirus 2.

Arterial stiffness, Long COVID, COVID-19, Vascular ageing, Sex differences
Issue Section:
Clinical Research > Epidemiology, Prevention, And Health Care Policies

See the editorial comment for this article ‘COVID-19 and vascular ageing: an accelerated yet partially reversible clock?', by S. Bukhari et al., https://doi.org/10.1093/eurheartj/ehaf590.
 
Last edited:

News Release 17-Aug-2025

Covid infection ages blood vessels, especially in women​

Peer-Reviewed Publication
European Society of Cardiology


image:

Portrait of researcher Professor Rosa Maria Bruno


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Credit: Rosa Maria Bruno / European Heart Journal

A Covid infection, particularly in women, may lead to blood vessels aging around five years, according to research published in the European Heart Journal [1] today (Monday).



Blood vessels gradually become stiffer with age, but the new study suggests that Covid could accelerate this process. Researchers say this is important since people with stiffer blood vessels face a higher risk of cardiovascular disease, including stroke and heart attack.



The study was led by Professor Rosa Maria Bruno from Université Paris Cité, France. She said: “Since the pandemic, we have learned that many people who have had Covid are left with symptoms that can last for months or even years. However, we are still learning what’s happening in the body to create these symptoms.



“We know that Covid can directly affect blood vessels. We believe that this may result in what we call early vascular ageing, meaning that your blood vessels are older than your chronological age and you are more susceptible to heart disease. If that is happening, we need to identify who is at risk at an early stage to prevent heart attacks and strokes.”



The study included 2,390 people from 16 different countries (Austria, Australia, Brazil, Canada, Cyprus, France, Greece, Italy, Mexico, Norway, Turkey, UK and US) who were recruited between September 2020 to February 2022. They were categorised according to whether they had never had Covid, had recent Covid but were not hospitalised, hospitalised for Covid on a general ward or hospitalised for Covid in an intensive care unit.



Researchers assessed each person’s vascular age with a device that measures how quickly a wave of blood pressure travels between the carotid artery (in the neck) and femoral arteries (in the legs), a measure called carotid-femoral pulse wave velocity (PWV). The higher this measurement, the stiffer the blood vessels and the higher the vascular age of a person. Measurements were taken six months after Covid infection and again after 12 months.



Researchers also recorded demographic information such as patient’s sex, age and other factors that can influence cardiovascular health.



After taking these factors into consideration, researchers found that all three groups of patients who had been infected with Covid, including those with mild Covid, had stiffer arteries, compared to those who had not been infected. The effect was greater in women than in men and in people who experienced the persistent symptoms of long Covid, such as shortness of breath and fatigue.



The average increase in PWV in women who had mild Covid was 0.55 meters per second, 0.60 in women hospitalised with Covid, and 1.09 for women treated in intensive care. Researchers say

an increase of around 0.5 meters per second is “clinically relevant” and equivalent to ageing around five years, with a 3% increased risk of cardiovascular disease, in a 60-year-old woman.



People who had been vaccinated against Covid generally had arteries that were less stiff than people who were unvaccinated. Over the longer term, the vascular ageing associated with Covid infection seemed to stabilise or improve slightly.



Professor Bruno said: “There are several possible explanations for the vascular effects of Covid. The Covid-19 virus acts on specific receptors in the body, called the angiotensin-converting enzyme 2 receptors, that are present on the lining of the blood vessels. The virus uses these receptors to enter and infect cells. This may result in vascular dysfunction and accelerated vascular ageing. Our body’s inflammation and immune responses, which defend against infections, may be also involved.



“One of the reasons for the difference between women and men could be differences in the function of the immune system. Women mount a more rapid and robust immune response, which can protect them from infection. However, this same response can also increase damage to blood vessels after the initial infection.



“Vascular ageing is easy to measure and can be addressed with widely available treatments, such as lifestyle changes, blood pressure-lowering and cholesterol-lowering drugs. For people with accelerated vascular ageing, it is important to do whatever possible to reduce the risk of heart attacks and strokes.”



Professor Bruno and her colleagues will continue to follow the participants over the coming years to establish whether the accelerated vascular ageing they have found leads to an increased risk of heart attacks and strokes in the future.



In an accompanying editorial [2] Dr Behnood Bikdeli from Harvard Medical School, Boston, USA and colleagues said: “Although the acute threat of the COVID-19 pandemic has waned, a new challenge emerged in its aftermath: post-acute COVID-19 syndrome. Defined by the World Health Organization as symptoms appearing three months post-infection and lasting at least two months, studies suggest that up to 40% of initial COVID-19 survivors develop this syndrome.



“This large, multicentre, prospective cohort study enrolled 2390 participants from 34 centres to investigate whether arterial stiffness, as measured by PWV, persisted in individuals with recent COVID-19 infection. […] sex-stratified analyses revealed striking differences: females across all COVID-19-positive groups had significantly elevated PWV, with the highest increase (+1.09 m/s) observed in those requiring ICU admission.



“The CARTESIAN study makes the case that COVID-19 has aged our arteries, especially for female adults. The question is whether we can find modifiable targets to prevent this in future surges of infection, and mitigate adverse outcomes in those afflicted with COVID-19-induced vascular ageing.”


Journal​

European Heart Journal

DOI​

10.1093/eurheartj/ehaf430

Method of Research​

Observational study

Subject of Research​

People

Article Title​

Accelerated vascular ageing after COVID-19 infection: the CARTESIAN study

Article Publication Date​

18-Aug-2025
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