Atherosclerosis, the gradual buildup of plaque within the arteries that causes most cardiovascular diseases, 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 otherwise healthy-looking young adults, and that it is considerably more widespread than previously thought.
The research has been led by Professor Henning Bundgaard, Professor of Cardiology at the Rigshospitalet in Copenhagen, Denmark, and Dr. Borja Ibáñez, scientific director of the Carlos III National Cardiovascular Research Center, CNIC, cardiologist at the Jiménez Díaz Foundation University Hospital and group leader of the CIBERCV.
Among more than 16,000 participants without symptoms or a previous diagnosis of cardiovascular disease, the researchers detected atherosclerotic plaques in 57.1%. The findings were presented in a Hot Line session at the ESC 2026 Congress and published at the same time in The New England Journal of Medicine.
Mapping occult atherosclerosis across the adult lifespan
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 is carried out through a collaboration between Rigshospitalet, other Danish hospitals and the CNIC in Spain.
Professor Bundgaard explains that “REACT’s vision is to transform primary cardiovascular prevention through a precision medicine approach based on the early identification of atherosclerosis.”
The Novo Nordisk Foundation granted up to €23 million to support the first phase of the initiative.
Atherosclerosis is the main 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 diseases kill nearly 20 million people worldwide each year, and atherosclerosis is responsible for the majority of those deaths.
One of the challenges is that the disease can develop silently for decades. Plaque can continue to build up inside the arteries without producing obvious warning signs.
Search for diseases instead of estimating risk
Professor Ibáñez said: “The REACT study is based on a simple but revolutionary idea: moving from the current model, which estimates the probability of cardiovascular disease based on traditional risk factors such as blood pressure, cholesterol and smoking, towards a new paradigm in which the disease is detected directly by imaging before it causes symptoms. In this model, preventive interventions and treatment of risk factors could be guided by the actual presence of silent atherosclerosis instead of relying solely on an indirect estimate of risk. The “The first step in this ambitious effort was to determine the true prevalence of silent atherosclerosis in the three major vascular territories and throughout adult life, something we are now reporting.”
In other words, rather than relying solely on factors like cholesterol, smoking, and blood pressure to estimate a person’s future cardiovascular risk, researchers want to determine whether plaque is already present.
REACT is expected to last eight years and two phases. Phase 1 (REACT-DETECT) began in 2024 and, if funding is awarded, Phase 2 (REACT-PROTECT) is planned to run from 2027 to 2032.
The current results come from Phase 1, which researchers say provides the most complete 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 between 18 and 70 years old in Denmark and Spain. None had a known history of atherosclerotic cardiovascular disease.
Each participant underwent advanced imaging designed to identify plaque in three main areas: the carotid arteries in the neck, the femoral arteries in the legs, and the coronary arteries that supply blood to 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.
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 increased steadily with age. Among participants ages 60 to 70, about 9 in 10 had atherosclerosis.
Ultrasound Could Offer an Easier Way to Screen
Another important pattern emerged from the images. Most participants who had atherosclerosis in the coronary arteries also had plaque in the carotid or femoral arteries.
That overlap could have important implications for future detection. Imaging the carotid and femoral arteries with ultrasound is easier, faster, and non-invasive compared to performing CT scans to examine the coronary arteries.
“In the paradigm we propose, portable ultrasound devices usable by any health professional will become the standard tool for the detection of atherosclerosis from the early stages of adult life,” said Dr. Ibáñez.
Men and women show different patterns
The study also identified notable differences in how atherosclerosis appeared throughout life in men and women.
Among men, prevalence began to increase at younger ages. Their overall pattern of atherosclerosis appeared five to ten years ahead of the pattern seen in women.
Women showed their greatest increase between ages 40 and 60, a period that largely overlaps with the menopausal transition.
The researchers say these differences underscore the need to investigate cardiovascular prevention strategies that take both sex and life stage into account.
Traditional risk scores miss many existing cases
One of the most important findings of the study 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 that a person may appear to have relatively low cardiovascular risk by 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 a 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 early stages, we will be able to intervene earlier, 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 if the disease was already present. REACT shows that atherosclerosis can be detected decades before clinical manifestations appear and provides the most complete atlas of the evolution of the disease throughout adult life.”
Test whether early detection improves outcomes
Professor Bundgaard added that the results create the scientific basis needed to test whether this proposed preventative 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 an image-guided preventive strategy, 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.
The investigators intend to launch a large randomized clinical trial testing whether image-guided prevention can slow or reduce the systemic progression of atherosclerosis. The long-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 expanding REACT beyond Europe to determine whether the findings hold in 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 around the world,” said Dr. Ibáñez.
REACT is based on the previous PESA-CNIC-Santander study led by Dr. Valentín Fuster, General Director of the 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 expands research to much younger age groups in an effort to understand when the disease begins to emerge.
“PESA has shown us that atherosclerotic disease is present in many middle-aged people and is associated with lifestyle patterns. At REACT, we wanted to investigate how it arises at much younger ages. For years, we have proposed that early intervention in atherosclerosis could not only prevent its progression but could even make it possible to cure the disease. REACT will answer this question,” said Dr. Fuster.