More than half of apparently healthy adults carry silent atherosclerosis, according to the REACT study presented at the ESC Congress 2026 and published simultaneously in the New England Journal of Medicine. Researchers evaluated nearly 17,000 adults across Denmark and Spain, finding the systemic condition progresses along distinct, sex-specific timelines.
Imaging Uncovers Hidden Atherosclerosis in 17,000 Adults
Around 20 million people die from cardiovascular disease (CVD) every year, as reported by the World Health Organization. For decades, medicine has estimated a patient’s cardiovascular risk using conventional factors like age, sex, smoking status, blood pressure, and cholesterol levels. That paradigm relies on an estimation rather than knowledge of the presence of the actual disease.
The observational REACT initiative set out to change that approach by using advanced imaging to detect silent atherosclerosis in adults without any known history of cardiovascular disease. Led by Professor Henning Bundgaard from Rigshospitalet – Copenhagen University Hospital in Denmark and Professor Borja Ibanez from Centro Nacional de Investigaciones Cardiovasculares in Madrid, Spain, the cross-sectional study enrolled 16,808 participants across Denmark and Spain with a mean age of 45.
Investigators deployed three-dimensional vascular ultrasound to map carotid arteries in the neck and femoral arteries in the leg, while examining heart arteries using computed tomography angiography and calcification status. Across the entire cohort, 57 percent of participants harbored undiscovered atherosclerotic plaques.
Sex-Specific Trajectories and Age-Related Prevalence Curves
The data reveal a stark age-related progression that takes shape long before clinical symptoms appear. Silent atherosclerosis was detected in roughly one in 13 participants aged 18 to 29, climbing steadily in an S-shaped curve until reaching approximately 9 out of 10 individuals between the ages of 60 and 70.
Men and women experience this accumulation along diverging timelines. Atherosclerosis prevalence rises earlier in men, whereas women exhibit a later, steep midlife acceleration that typically coincides with the age of menopause. Plaque volume expands exponentially with age, though isolated coronary-artery disease remains uncommon across all ages, and among younger participants, plaque is most often peripheral and confined to a single vascular territory.
“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
Researchers also evaluated how effectively standard risk calculators identify high-risk individuals among this population. The SCORE2 risk tool classified only a small minority of participants with confirmed silent atherosclerosis as high risk, with a marked lack among younger participants.
Toward Precision Prevention and Portable Screening Protocols
Current primary prevention strategies rely on risk factor scores that can miss opportunities to prevent cardiovascular events in individuals in whom atherosclerosis has built up many years previously. Direct imaging changes that dynamic by verifying the physical presence of disease before a heart attack, stroke or sudden cardiac death occurs.
Investigators emphasize that identifying and treating these hidden plaques early could significantly reduce the global burden of cardiovascular disease. The team envisions a clinical future where portable ultrasound equipment allows healthcare professionals to screen for cardiovascular disease from early stages of life.
“Identifying and treating silent atherosclerosis as early as possible could help reduce the global burden of [cardiovascular disease]. 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.”
Professor Henning Bundgaard, Rigshospitalet – Copenhagen University Hospital
These findings lay the groundwork for the second phase of the REACT initiative. A major randomized trial is currently planned to determine whether imaging-guided treatment using handheld ultrasound scanners can improve clinical standards and support a precision medicine approach to cardiovascular care.
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