Silent atherosclerosis was detectable from early adulthood and showed sex-specific patterns of growth with age, according to results from the REACT study presented in a Hot Line session today at ESC Congress 2026 and published simultaneously in the New England Journal of Medicine.
Across the globe, around 20 million people die from cardiovascular disease (CVD) every year and most of these deaths are due to atherosclerosis. Atherosclerosis may begin in early adulthood and remain clinically silent for decades before manifesting mainly as a heart attack, stroke or sudden cardiac death.
Investigating the presence of silent atherosclerosis across the adult lifespan was the main aim of the first part of the prospective observational study, the REACT Initiative, which is led by Professor Henning Bundgaard from Rigshospitalet – Copenhagen University Hospital, Denmark and Professor Borja Ibanez from Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
“Currently, a person’s risk of developing atherosclerotic CVD is estimated according to their risk factors, such as age, sex, smoking status, blood pressure and cholesterol levels, and this determines whether primary prevention strategies are prescribed,” explained study presenter, Professor Bundgaard. “This approach relies on an estimation – not on knowledge of the presence of the actual disease (i.e., atherosclerotic plaques) – and we may be missing important opportunities to prevent cardiovascular events in individuals in whom atherosclerosis has built up many years previously,” he noted.
In REACT, different imaging modalities were used to measure silent atherosclerosis in adults without known CVD aged 18 to 70 years old from Denmark and Spain in a cross-sectional study. Three-dimensional vascular ultrasound was used to assess atherosclerosis in carotid arteries (in the neck) and femoral arteries (in the leg); the heart arteries (coronaries) were imaged using computed tomography (CT) angiography and calcification status.
The study included 16,808 adults who had a mean age of 45 years. Participants were balanced across age decades according to a pre-specified plan with equal proportions of women and men in each age decade.
The researchers found silent atherosclerosis in 57.1% of participants. It was already detectable in approximately 1 in 13 participants aged 18–29 years and was found in 9 out of 10 participants aged 60–70 years, with prevalence increasing with age in an S-shaped curve.
Atherosclerosis prevalence increased earlier in men, whereas women showed a later and particularly steep midlife increase, around the typical age of menopause. In addition, increasing age was associated with expansion of atherosclerosis and an exponential increase in age-related atherosclerotic plaque volume. Most individuals with silent atherosclerosis in their heart had atherosclerosis in their neck and/or leg arteries.
These data from multiple locations support the concept of silent atherosclerosis as a systemic, progressive disease process with men showing an approximately 5-to-10-year earlier atherosclerotic trajectory than women.”
Professor Henning Bundgaard, Rigshospitalet – Copenhagen University Hospital, Denmark
The researchers also examined the extent to which conventional cardiovascular risk assessment classifies participants with silent atherosclerosis as high risk. They found that the SCORE2 risk tool classified only a small minority of participants with silent atherosclerosis as high risk, with a marked lack among younger participants.
Professor Bundgaard concluded: “Identifying and treating silent atherosclerosis as early as possible could help reduce the global burden of CVD. Our findings support further prospective studies to investigate whether imaging-guided treatment of those with early evidence of disease –detected using a handheld ultrasound scanner – can improve current standards. If successful, this could support a precision medicine approach to atherosclerotic cardiovascular disease.” Based on the presented findings, a major randomised trial is planned as part of the second phase of the REACT Initiative.
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