Atherosclerosis, the progressive buildup of fatty plaque inside arteries, often begins long before any symptoms appear. A major new international study now shows that this hidden damage is already present in a significant proportion of apparently healthy young adults.
Among more than 16,000 symptom-free adults, researchers detected subtle arterial plaque in over half of participants. The findings provide one of the most detailed pictures to date of how silent atherosclerosis develops across the adult lifespan.
Large-scale REACT project unveiled
The data come from the first phase of REACT, a long-term research initiative funded by the Novo Nordisk Foundation. The project is led by Professor Henning Bundgaard of Rigshospitalet in Copenhagen and Dr. Borja Ibáñez of Spain’s CNIC and Hospital Universitario Fundación Jiménez Díaz.
REACT aims to transform cardiovascular prevention by shifting from estimating risk to directly detecting early disease. Backed by up to EUR 23 million in initial funding, the eight-year programme is divided into two phases, with the first focused on mapping disease and the second on testing new prevention strategies.
Cardiovascular disease remains the world’s leading cause of death, claiming nearly 20 million lives each year. Most of these deaths are driven by atherosclerosis, yet the underlying process can progress silently for decades before causing a heart attack, stroke or sudden cardiac death.
Imaging reveals early-life artery damage
For REACT’s first phase, researchers recruited 16,808 adults between the ages of 18 and 70 in Denmark and Spain, none of whom had diagnosed atherosclerotic cardiovascular disease. Each participant underwent advanced imaging of the carotid arteries in the neck, femoral arteries in the legs and coronary arteries of the heart.
Researchers combined these scans with detailed assessments of traditional cardiovascular risk factors, blood biomarkers and retinal images, creating an extensive dataset. The analysis revealed that 57.1% of participants already had detectable plaque in at least one major arterial territory.
The findings indicate that atherosclerosis can begin much earlier than many people assume. Around 1 in 13 participants aged 18 to 29 had arterial plaque despite feeling healthy and having no history of cardiovascular disease.
Prevalence rises steeply with age
The burden of silent atherosclerosis increased consistently with age. Among participants aged 60 to 70, approximately 9 in 10 had detectable plaque somewhere in their vascular system. Many of these individuals had no symptoms or formal cardiovascular diagnosis.
Researchers also found substantial overlap between plaque in the coronary arteries and plaque in the carotid or femoral arteries. This pattern suggests that more accessible imaging of the neck and leg arteries could help identify people more likely to have coronary disease.
Imaging the coronary arteries typically requires computed tomography, which is more complex and expensive than ultrasound. By contrast, ultrasound of the carotid and femoral vessels is noninvasive, relatively quick and increasingly available in outpatient settings.
Ultrasound as a frontline screening tool
Based on these findings, the REACT team envisions portable ultrasound becoming a core tool in routine cardiovascular screening for adults. Such devices can be operated by a range of healthcare professionals, potentially allowing earlier detection in primary care.
Under this proposed approach, clinicians would not rely solely on age, blood pressure, cholesterol and smoking status to estimate cardiovascular risk. Instead, they could directly visualize the arteries and tailor prevention according to the actual presence and extent of plaque.
Supporters of this strategy argue that earlier identification of disease could allow more targeted lifestyle counselling, optimized cholesterol-lowering treatment and closer follow-up for people who are already developing atherosclerosis.
Men and women show different patterns
The study also identified distinct patterns in men and women. Among men, silent atherosclerosis tended to appear earlier, with a higher prevalence already evident at younger ages compared with women.
Women showed a sharper increase in plaque between the ages of 40 and 60, a period that broadly coincides with the menopausal transition. This supports previous evidence that hormonal changes may influence cardiovascular risk trajectories.
The authors say these sex-specific patterns point to the potential need for more tailored screening thresholds and prevention strategies that consider both biological sex and life stage rather than applying uniform criteria.
Traditional risk scores fall short
One of the study’s most concerning findings involved conventional cardiovascular risk calculators, including SCORE2 and similar tools. According to the investigators, these scores identified only a minority of people who already had silent atherosclerosis detected through imaging.
This means that someone can be classified as having low or moderate cardiovascular risk under current guidelines while plaque is already accumulating inside the arteries. Over time, this unseen damage can progress and potentially lead to clinical cardiovascular events.
The authors argue that this gap highlights the limitations of risk scores based solely on statistical associations between risk factors and outcomes. Direct imaging, they suggest, could provide a more precise picture of who already has early vascular disease.
Testing if earlier detection saves lives
While the findings show that hidden atherosclerosis is common, particularly later in adulthood, a crucial question remains: whether detecting and treating it earlier actually improves long-term outcomes. REACT’s second phase is designed to investigate this issue.
If fully funded, REACT-PROTECT, planned for 2027 to 2032, will launch a large randomized clinical trial comparing standard risk-factor-based prevention with an imaging-guided strategy that uses early plaque detection to guide treatment.
Researchers aim to determine whether this precision approach can slow the systemic progression of atherosclerosis and reduce heart attacks, strokes and related complications more effectively than current preventive strategies.
Global expansion and earlier origins
The REACT project is also expanding beyond Europe. Collaborations are being developed with research groups in India, Singapore, Tanzania and Mexico to determine whether patterns observed in Denmark and Spain are also seen in populations with different genetics, lifestyles and healthcare systems.
REACT builds on earlier findings from the PESA-CNIC-Santander study, which showed that many middle-aged adults already had subclinical atherosclerosis associated with lifestyle patterns. The new data extend this picture into substantially younger age groups.
By mapping when and where arterial plaque first appears, the REACT team hopes to determine whether very early intervention could not only slow atherosclerosis but potentially reverse some of its earliest stages. Results from future trials will be critical for answering that question and determining whether cardiovascular prevention guidelines should eventually change.
