Atherosclerosis, the gradual buildup of plaque inside arteries that drives most cardiovascular disease, can begin many years before a person notices any symptoms. Now, a large international study suggests that this hidden disease is already present in some young adults who otherwise appear healthy, and that it is considerably more widespread than previously recognized.
The research was led by Professor Henning Bundgaard, Professor of Cardiology at Rigshospitalet in Copenhagen, Denmark, and Dr. Borja Ibáñez, Scientific Director of the Centro Nacional de Investigaciones Cardiovasculares Carlos III, CNIC, cardiologist at Hospital Universitario Fundación Jiménez Díaz and a group leader at CIBERCV.
Among more than 16,000 participants with no symptoms or previous cardiovascular disease diagnosis, researchers detected atherosclerotic plaques in 57.1%. The findings were presented in a Hot Line session at ESC Congress 2026 and published at the same time in The New England Journal of Medicine.
Mapping Hidden Atherosclerosis Across Adult Life
The findings come from the first phase of REACT, one of the largest efforts yet to examine how silent atherosclerosis develops throughout adulthood. The international project is funded by the Novo Nordisk Foundation and carried out through a collaboration involving Rigshospitalet, other Danish hospitals and CNIC in Spain.
Professor Bundgaard explains that “the vision of REACT is to transform primary cardiovascular prevention through a precision medicine approach based on the early identification of atherosclerosis.”
The Novo Nordisk Foundation awarded up to EUR 23 million to support the initiative’s first phase.
Atherosclerosis is the primary underlying cause of cardiovascular disease, which can eventually appear as a heart attack, stroke or sudden death. Having arterial plaque does not mean that a person will inevitably develop symptomatic disease. However, cardiovascular disease kills nearly 20 million people around the world each year, with atherosclerosis responsible for most of those deaths.
One of the challenges is that the disease can develop quietly for decades. Plaque may continue accumulating inside the arteries without producing any obvious warning signs.
Looking for Disease Instead of Estimating Risk
Professor Ibáñez stated that “the REACT study is based on a simple but revolutionary idea: moving from the current model, which estimates the probability of cardiovascular disease on the basis of traditional risk factors such as blood pressure, cholesterol and smoking, towards a new paradigm in which the disease is detected directly through imaging before it causes symptoms. In this model, preventive interventions and the treatment of risk factors could be guided by the actual presence of silent atherosclerosis rather than relying solely on an indirect estimate of risk. The first step in this ambitious endeavour was to determine the actual prevalence of silent atherosclerosis in all three major vascular territories and across the entire adult lifespan, something that we are reporting now.”
In other words, rather than relying only on factors such as cholesterol, smoking and blood pressure to calculate someone’s future cardiovascular risk, the researchers want to determine whether plaque is already present.
REACT is expected to span eight years and two phases. Phase 1 (REACT-DETECT) began in 2024 and, if funding is granted, Phase 2 (REACT-PROTECT) is planned to run from 2027 through 2032.
The current results come from Phase 1, which researchers say provides the most comprehensive picture yet of where silent atherosclerosis appears in the body, how common it is at different ages, and how its prevalence differs between women and men.
Atherosclerosis Is Already Present in Young Adults
For the first phase, researchers enrolled 16,808 people ages 18 to 70 in Denmark and Spain. None had a known history of atherosclerotic cardiovascular disease.
Every participant underwent advanced imaging designed to identify plaque in three major areas: the carotid arteries in the neck, the femoral arteries in the legs and the coronary arteries supplying the heart.
The researchers also examined cardiovascular risk factors and blood biomarkers, collected samples for omics studies and analyzed retinal images. Together, these measurements created one of the most extensive databases on atherosclerosis assembled to date.
The scans showed that atherosclerosis can appear surprisingly early in adulthood. About 1 in 13 participants ages 18 to 29 had signs of the disease in at least one artery.
The prevalence then climbed steadily with age. Among participants ages 60 to 70, about 9 in 10 had atherosclerosis.
Ultrasound Could Offer a Simpler Way to Screen
Another important pattern emerged from the imaging. Most participants who had atherosclerosis in their coronary arteries also showed plaque in the carotid or femoral arteries.
That overlap could have significant implications for future screening. Imaging the carotid and femoral arteries with ultrasound is easier, quicker and noninvasive compared with performing CT scans to examine the coronary arteries.
“In the paradigm we propose, portable ultrasound devices usable by any healthcare professional will become the standard tool for atherosclerosis screening from the early stages of adult life,” Dr. Ibáñez said.
Men and Women Show Different Patterns
The study also identified notable differences in how atherosclerosis appeared across the lifespan in men and women.
Among men, prevalence began increasing at younger ages. Their overall pattern of atherosclerosis appeared about five to ten years ahead of the pattern seen in women.
Women showed their sharpest rise between ages 40 and 60, a period that broadly overlaps with the menopausal transition.
The researchers say these differences underscore the need to investigate cardiovascular prevention strategies that account for both sex and stage of life.
Traditional Risk Scores Miss Many Existing Cases
One of the study’s most consequential findings involved conventional cardiovascular risk assessment.
Current methods, including risk scores such as SCORE2, identified only a small proportion of people who already had silent atherosclerosis. That suggests a person can appear to have relatively low cardiovascular risk according to traditional measures while plaque is already developing inside the arteries.
According to Dr. Ibáñez, the findings point toward a potentially different approach to preventing cardiovascular disease.
“For decades, we have estimated cardiovascular risk using factors such as age, blood pressure and cholesterol. This study shows that we can now go one step further and detect the disease directly before it causes a heart attack or stroke.”
He added: “The future of cardiovascular prevention must be more precise and personalized. If we identify atherosclerosis in its earliest stages, we will be able to intervene sooner, tailor treatment more effectively and reduce the burden of cardiovascular disease.”
Professor Bundgaard believes the findings could provide an opportunity to rethink how cardiovascular prevention is carried out.
“Until now, preventive decisions have been based on an estimate of risk, but we did not know whether the disease was already present. REACT shows that atherosclerosis can be detected decades before clinical manifestations appear and provides the most comprehensive atlas of the evolution of the disease across adult life.”
Testing Whether Earlier Detection Improves Outcomes
Professor Bundgaard added that the results create the scientific foundation needed to test whether this proposed preventive approach actually improves health outcomes.
“Identifying and treating silent atherosclerosis as early as possible is essential to reducing the global burden of cardiovascular disease. Our results support prospective studies evaluating whether a preventive strategy guided by imaging, including the use of portable ultrasound, can improve current standards. If confirmed, this would bring precision medicine to the most common cardiovascular disease.”
If funded, the second phase of REACT, planned for 2027 to 2032, will examine that question directly.
Researchers intend to launch a large randomized clinical trial testing whether prevention guided by imaging can slow or reduce the systemic progression of atherosclerosis. The longer term goal is to determine whether this strategy can prevent heart attacks, strokes and other cardiovascular events more effectively than current practice.
Expanding REACT Around the World
The research team is also extending REACT beyond Europe to determine whether the findings hold across different populations.
“REACT is expanding its impact around the world. We have established close collaborations with India, Singapore, Tanzania and Mexico to validate these results in populations across the globe,” Dr. Ibáñez said.
REACT builds on the earlier PESA-CNIC-Santander study led by Dr. Valentin Fuster, Director General of CNIC, who is also directly involved in REACT.
That work found that atherosclerosis was already present in many middle aged adults and was associated with lifestyle patterns. REACT extends the investigation into much younger age groups in an effort to understand when the disease first begins to emerge.
“PESA has shown us that atherosclerotic disease is present in many middle-aged people and is associated with lifestyle patterns. In REACT, we wanted to investigate how it emerges at much younger ages. For years, we have proposed that early intervention in atherosclerosis could not only prevent its progression but might even make it possible to cure the disease. REACT will answer this question,” Dr. Fuster said.