Silent atherosclerosis is detectable in more than half of apparently healthy adults through early adulthood vascular imaging, according to findings from the REACT study presented at the ESC Congress 2026 and published in the New England Journal of Medicine, revealing sex-specific progression trajectories that could reshape cardiovascular disease prevention.
Cardiovascular disease claims around 20 million lives every year, and most of these deaths are due to atherosclerosis, a condition where plaque builds up inside the arteries. For decades, clinicians have assessed a person’s risk of developing atherosclerotic cardiovascular disease by evaluating traditional factors such as age, sex, smoking status, blood pressure, and cholesterol levels. This standard approach determines whether primary prevention strategies are prescribed.
However, that traditional methodology relies strictly on estimation rather than direct knowledge of whether the disease is actually present in the body. A major international initiative set out to test whether looking directly for the disease changes the equation. Results from the first part of the prospective observational REACT study—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—were presented during a Hot Line session at the Congress of the European Society of Cardiology and simultaneously published in the New England Journal of Medicine.
What the REACT Study Discovered About Silent Plaque Formation
The cross-sectional study enrolled 16,808 adults aged 18 to 70 years without known atherosclerotic cardiovascular disease from Denmark and Spain, maintaining a balanced distribution across age decades with equal proportions of women and men. Investigators utilized multiple imaging modalities to check for hidden disease: three-dimensional vascular ultrasound examined the carotid arteries in the neck and femoral arteries in the leg, while computed tomography angiography and calcification status assessed the coronary arteries in the heart.
The data revealed that silent atherosclerosis was present in 57.1 percent of all participating adults. The condition was already detectable in approximately 1 in 13 participants aged 18 to 29 years, and its prevalence increased with age in an S-shaped curve until reaching about 9 out of 10 individuals between the ages of 60 and 70.
“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 observed distinct sex-specific patterns in how the condition develops. Atherosclerosis prevalence increased earlier in men, whereas women showed a later and particularly steep midlife increase, which aligned around the typical age for menopause. Furthermore, increasing age brought an expansion of atherosclerosis and an exponential rise in atherosclerotic plaque volume. Among younger participants, the disease was most often peripheral and confined to a single vascular territory, and isolated coronary-artery atherosclerosis remained uncommon across all age groups.
Evaluating Conventional Risk Tools Against Direct Imaging
A critical component of the prospective observational study involved examining how well standard cardiovascular risk assessment tools classify participants who actually harbor hidden plaque. Investigators found that the SCORE2 risk tool classified only a small minority of participants with silent atherosclerosis as high risk, exhibiting a marked lack among younger individuals.
By relying purely on risk factor estimation rather than direct detection of actual atherosclerotic plaques, modern medicine may be missing important opportunities to prevent cardiovascular events in individuals in whom atherosclerosis has built up many years previously.
Toward Portable Ultrasound Screening and Personalized Medicine
Lead investigators noted that identifying and treating silent atherosclerosis as early as possible could significantly reduce the global burden of cardiovascular disease.
Looking ahead, the initiative is already preparing its next major milestone. Based on the findings presented at the ESC Congress, a major randomised trial is planned as part of the second phase of the REACT initiative. This upcoming trial will investigate whether imaging-guided treatment for individuals caught with early evidence of disease using a handheld ultrasound scanner can improve current standards of care and establish a true precision medicine approach to atherosclerotic cardiovascular disease.
