Atherosclerosis may begin shockingly early, with artery scans revealing hidden plaque in about one in 13 adults before age 30.
An international study of 16,808 adults found that silent atherosclerosis is far more common than symptoms or routine risk assessments suggest. Advanced scans detected plaque in 57.1% of participants with no known cardiovascular disease, revealing how quietly the condition can take hold across adulthood.
These findings challenge the idea that prevention should rely entirely on predicting who might become ill. Instead, researchers envision using medical imaging to identify the disease itself while there is still time to slow its progression.
Mapping a Disease That Hides for Decades
Atherosclerosis develops when fats, cholesterol, and other substances accumulate within artery walls. As plaques grow or rupture, they can restrict blood flow or trigger clots that cause heart attacks and strokes. The condition can progress silently for decades, so a catastrophic cardiovascular event may be its first visible sign.
Cardiovascular disease kills nearly 20 million people worldwide each year, with atherosclerosis responsible for most of those deaths. Although not everyone with arterial plaque will suffer a heart attack or stroke, researchers still need to determine whether early detection can reveal who is most likely to benefit from preventive care.
The results were presented during a Hot Line session at ESC Congress 2026 and published simultaneously in The New England Journal of Medicine. The research was led by Professor Henning Bundgaard of Rigshospitalet in Copenhagen and Dr. Borja Ibáñez of CNIC, who is also affiliated with Hospital Universitario Fundación Jiménez Díaz and CIBERCV.
The data come from the first phase of REACT, one of the largest projects created to track silent atherosclerosis across adult life. The initiative brings together Rigshospitalet, other Danish hospitals, and CNIC in Spain, with funding from the Novo Nordisk Foundation. The foundation awarded up to EUR 23 million for the project’s first phase.
Looking for Disease Instead of Estimating Risk
Most cardiovascular prevention currently begins with risk calculations based on factors such as age, cholesterol, blood pressure, and smoking. These scores estimate the likelihood of a future cardiovascular event, but they do not directly show whether plaque has already formed.
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”.
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 endeavor 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.”
REACT is expected to span eight years and consists of two stages. Phase 1 (REACT-DETECT) began in 2024. If funding is approved, Phase 2 (REACT-PROTECT) will run from 2027 to 2032.
More Than 16,000 Adults Underwent Imaging
For the first phase, researchers recruited 16,808 people ages 18 to 70 in Denmark and Spain. None had a known history of atherosclerotic cardiovascular disease.
Each participant underwent advanced imaging of three major vascular regions. Researchers examined the coronary arteries supplying the heart, the carotid arteries in the neck, and the femoral arteries in the legs.
The team also collected information on cardiovascular risk factors, blood biomarkers, and retinal images, along with biological samples for omics research. These combined measurements produced one of the most detailed databases yet assembled on how atherosclerosis varies by age, sex, and location in the body.
The result is an extensive atlas of hidden arterial disease across adulthood. Although plaque became increasingly common with age, its appearance in approximately one in 13 participants aged 18 to 29 showed that the process can begin surprisingly early.
Ultrasound Could Make Screening More Practical
Most people with coronary artery plaque also had atherosclerosis in the carotid or femoral arteries. Coronary arteries are generally examined with CT, while arteries in the neck and legs can be assessed more easily with noninvasive ultrasound.
If plaque outside the heart reliably signals coronary disease, portable ultrasound could eventually offer a faster and more accessible way to identify people who may need further evaluation. Whether population screening improves health outcomes and justifies its costs still needs to be tested in prospective clinical trials.
“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.
Women and Men Followed Different Patterns
The disease appeared to advance earlier in men. Across the age range studied, their atherosclerotic profile was approximately five to 10 years ahead of the pattern observed in women.
Among women, the steepest rise occurred between ages 40 and 60, broadly overlapping with the menopausal transition. Hormonal changes, aging, and shifts in established cardiovascular risk factors may all contribute, although the current findings do not establish why the increase occurs.
Prevention could potentially become more effective if the timing and type of assessment were adapted to sex and stage of life.
Risk Scores Missed Much of the Hidden Plaque
Conventional prediction methods, including the SCORE2 risk calculator, identified only a small share of participants who already had silent atherosclerosis. A person can therefore receive a relatively reassuring risk estimate even when imaging shows that plaque formation has begun.
“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,” Dr. Ibáñez said.
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 said the atlas exposes a limitation that has long shaped preventive care. “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.”
The Next Phase Will Test Whether Imaging Saves Lives
Detecting more plaque is not by itself proof that screening improves health. Researchers must still determine whether acting on imaging results can slow the disease and prevent cardiovascular events without producing unnecessary treatment or testing.
“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,” Professor Bundgaard said.
If funded, REACT-PROTECT will address that question through a large randomized clinical trial from 2027 to 2032. Investigators will compare an imaging-guided precision prevention strategy with current practice to determine whether it can halt or reduce the systemic progression of atherosclerosis and, over the long term, prevent more heart attacks, strokes, and other cardiovascular events.
The researchers are also working to establish whether the initial findings apply beyond the European populations studied. “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.
Building on an Earlier Study of Middle Age
REACT extends the work of the PESA-CNIC-Santander study, led by Dr. Valentín Fuster, Director General of CNIC and a participant in the new project. PESA previously showed that silent atherosclerosis is common in middle age and is associated with lifestyle patterns.
“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.
Reference: “Prevalence of Silent Atherosclerosis across Adult Life” by Henning Bundgaard, Inés García-Lunar, Klaus F. Kofoed, Rasmus Hasselbalch, Carlos Nicolás Pérez-García, Joakim Bo Kunkel, Frederik Filip Stæger, Fátima Sánchez-Cabo, José J. Fuster, Virginia Mass, Javier Sánchez-González, Maja V. Kragh, Anna K. Ringgaard, Javier Valls-Monzó, Michael Huy Cuong Pham, Ana Devesa, Morten Sejer, Per Sigvardsen, Antonio Quesada, Charlotte Eberhard, Ana García-Álvarez, Lea Marie Pehrson, Álvaro Navarro-Guzmán, Simon Winther, Mathias Sørgaard, Marcos Gámez, Martin Lundsgaard, Cristina Pérez-Herreras, Ruth Frikke-Schmidt, Pedro L. Sánchez, Nikolaj Eldrup, Juan Torres-Macho, Morten Bøttcher, Valentin Fuster, Kasper K. Iversen and Borja Ibanez, 28 August 2026, New England Journal of Medicine.
DOI: 10.1056/NEJMoa2609059
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