Silent plaque appeared far earlier than routine prevention expects
More than half of 16,808 apparently healthy adults had silent atherosclerosis on imaging, and the disease was already detectable in about 1 in 13 people aged 18 to 29. The finding is difficult to ignore because atherosclerosis is not an abstract risk marker; it is the arterial substrate for most heart attacks, strokes and sudden cardiac deaths. Once plaque is present, the disease process has already started inside the vessel wall, often years before chest pain, neurologic symptoms or a first emergency department visit forces recognition.
The study, presented at ESC Congress 2026 and published in The New England Journal of Medicine, examined adults between 18 and 70 years of age in Denmark and Spain who had no known cardiovascular disease. Every participant underwent advanced imaging of the carotid, femoral and coronary arteries. Plaque was found in 57.1% overall. The age gradient was steep: prevalence rose from a surprisingly early signal in young adulthood to roughly 9 in 10 participants aged 60 to 70.
That pattern fits the biology of atherosclerosis. Arterial injury and lipid deposition begin long before symptoms, while inflammation and plaque remodeling continue quietly until lesions become large enough to narrow the lumen, rupture or trigger thrombosis. A person may feel entirely well while disease accumulates in multiple vascular beds.
Imaging exposed disease that traditional risk scores missed
The REACT project, funded in its first phase by the Novo Nordisk Foundation, was designed around a different preventive premise: detect the disease directly instead of estimating future risk from indirect markers alone. The cohort analysis suggests why that shift is being considered. Conventional tools, including risk scores such as SCORE2, identified only a small fraction of participants who already had plaque. In practical terms, a low or modest calculated risk score did not reliably exclude established arterial disease.
This matters because risk scores are built from population probabilities, not direct visualization. Blood pressure, cholesterol and smoking status remain clinically important, but they do not reveal whether plaque has already formed in a given person. Direct imaging does. By comparing risk estimates with actual arterial findings, REACT exposed a gap between probability-based prevention and disease-based prevention.
The investigators also built a broad data platform beyond vascular imaging. They collected cardiovascular risk factors, blood biomarkers, omics samples and retinal images, creating one of the most extensive atherosclerosis datasets assembled to date. That breadth should help separate surface-level risk from the biological signatures of active plaque formation, plaque burden and vascular distribution across adult life.
A short sentence captures the central clinical shock: hidden plaque was already present before most screening strategies would have flagged these adults.
Men, women and the geography of plaque burden
The study found clear sex differences across age bands. In men, prevalence began rising earlier, and the overall pattern of disease appeared about five to ten years ahead of the pattern seen in women. Women showed their sharpest rise between ages 40 and 60, a span that broadly overlaps the menopausal transition. Those differences are clinically meaningful because they suggest the timing of vascular risk accumulation is not identical across sexes, and a one-size-fits-all screening approach may miss important windows for prevention.
The distribution of plaque also has screening implications. Most participants with coronary atherosclerosis also had plaque in the carotid or femoral arteries. That overlap creates an opening for simpler vascular imaging pathways. Ultrasound of the carotid and femoral arteries is faster, noninvasive and more accessible than coronary CT in many settings. If plaque in peripheral arteries reliably tracks coronary involvement, ultrasound could become a practical first-line screening tool for detecting disease before symptoms emerge.
Dr. Borja Ibáñez described the proposed model as a move toward detecting disease directly through imaging rather than inferring it from risk factors alone. Professor Henning Bundgaard framed the long-term goal as a precision approach to primary prevention, in which treatment decisions are guided by the actual presence of atherosclerosis. The concept is straightforward enough at the bedside: if plaque is already there, preventive care can be targeted to the patient’s real arterial burden rather than to an estimate.
The next question is whether earlier detection changes outcomes
REACT is being developed in two phases across eight years. Phase 1, REACT-DETECT, defined how common silent atherosclerosis is across adult life. Phase 2, REACT-PROTECT, planned for 2027 through 2032 if funding is secured, is intended to test whether imaging-guided prevention can slow systemic progression of the disease and, later, prevent heart attacks and strokes more effectively than current practice.
That is the critical unanswered clinical step. Finding plaque earlier is valuable only if earlier detection changes management in a way that improves hard outcomes. Imaging could lead to earlier statin therapy, tighter blood pressure control, smoking cessation reinforcement and more individualized follow-up, but those assumptions still require randomized testing.
The researchers also plan to extend REACT internationally, with collaborations in India, Singapore, Tanzania and Mexico. External validation will matter because atherosclerosis does not develop in a vacuum; age structure, diet, smoking patterns, hypertension prevalence and access to prevention all shape how plaque burden appears in different populations.
For now, the data press against the old assumption that silent atherosclerosis is mostly a middle-aged or older-adult problem. The plaque burden was already measurable in young adulthood, and traditional risk scoring missed many of those cases. The study does not prove that every adult should undergo vascular imaging, but it does show that the disease often arrives long before standard prevention algorithms would expect it to be found.