REACT: Silent Atherosclerosis Widespread, Missed By Standard Risk Tools

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 at the European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, and published simultaneously in the New England Journal of Medicine.^1,2

Roughly 20 million people die of cardiovascular disease worldwide each year, and most of these deaths are attributable to atherosclerosis, which may begin in early adulthood and remain clinically silent for decades before manifesting as a heart attack, stroke, or sudden cardiac death.²

Prior estimates of subclinical atherosclerosis prevalence have relied heavily on single-territory imaging, most often carotid ultrasound alone. A recent systematic review and meta-analysis reported a pooled carotid plaque prevalence of just 5.2% among adults 18 to 45 years old.³

REACT Trial Design and Age-Related Prevalence of Silent Atherosclerosis

REACT is led by Henning Bundgaard, MD, DMSc, of Rigshospitalet, Copenhagen University Hospital, Denmark, and Borja Ibanez, MD, PhD, of the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. Investigating the presence of silent atherosclerosis across the adult lifespan was the main aim of this first, cross-sectional part of the prospective REACT Initiative.²

Investigators used 3-dimensional vascular ultrasonography to assess atherosclerosis in the carotid and femoral arteries, and coronary computed tomographic angiography with calcification status to assess the coronary arteries, in adults 18 to 70 years old without known cardiovascular disease (CVD) from Denmark and Spain.^1,2

The study included 16,808 adults with a mean age of 45 years, balanced across age decades with equal proportions of women and men in each decade.¹,² Silent atherosclerosis was found in 57.1% of participants overall.¹ It was already detectable in approximately 1 in 13 participants aged 18 to 29 years and was found in 9 out of 10 participants aged 60 to 70 years, with prevalence increasing with age in an S-shaped curve.²

In a press release, Bundgaard framed the findings against the limitations of standard risk-based prevention. "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," he said. "This approach relies on an estimation, not on knowledge of the presence of the actual disease, and we may be missing important opportunities to prevent cardiovascular events in individuals in whom atherosclerosis has built up many years previously.”

Sex-Specific Trajectory in Silent Atherosclerosis

Atherosclerosis prevalence increased earlier in men, while women showed a later and particularly steep midlife increase, around the typical age of menopause. Increasing age was also associated with expansion of atherosclerosis and an exponential increase in age-related atherosclerotic plaque volume, and most individuals with silent atherosclerosis in their heart also had atherosclerosis in their neck or leg arteries.²

"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," Bundgaard said.²

Conventional Risk Assessment Misses Silent Atherosclerosis

Investigators also examined the extent to which conventional cardiovascular risk assessment classifies participants with silent atherosclerosis as high risk. They found the SCORE2 risk tool classified only a small minority of participants with silent atherosclerosis as high risk, with a marked lack of high-risk classification among younger participants.²

"Identifying and treating silent atherosclerosis as early as possible could help reduce the global burden of CVD," Bundgaard concluded. "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 randomized trial is planned as part of the second phase of the REACT Initiative.²

References

1. Bundgaard H, García-Lunar I, Kofoed KF, et al; REACT Investigators. Prevalence of silent atherosclerosis across adult life. N Engl J Med. 2026. doi:10.1056/NEJMoa2609059

2. European Society of Cardiology. Early imaging of atherosclerosis identifies silent disease not captured by conventional risk assessment. Published August 29, 2026. Accessed August 29, 2026. https://www.escardio.org/news/press/press-releases/early-imaging-of-atherosclerosis-identifies-silent-disease-not-captured-by-conventional-risk-assessment/?filter43090=ArticleType.eq.press&page43090=1&page_size43090=20&sort43090=Date&sort_type43090=desc

3. Johri AM, Hill B, Grubic N, et al. The prevalence of carotid subclinical atherosclerosis according to age: a systematic review and meta-analysis of the young to middle-age. J Clin Lipidol. 2025. doi:10.1016/j.jacl.2025.10.069