Silent Atherosclerosis: New Research Shows Hidden Artery Plaque Is Common, Starts Young, and Grows Steadily With Age

Table of Contents

• Key Points
• What Is Silent Atherosclerosis and Why Does This Study Matter?
• Background: What Researchers Already Knew
• Study Methods: How the Research Was Conducted
• Who Took Part in the Study
• Key Finding: More Than Half of Adults Have Silent Atherosclerosis
• Men and Women Follow Different Timelines
• Where Plaque Collects: Neck, Legs, and Heart Arteries
• What This Means for Patients and Doctors
• Study Limitations: What This Research Could Not Show
• Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• In a study of 13,186 adults with no known heart disease, 57.1% had silent atherosclerosis in at least one vascular territory.
• Silent plaque was found even in adults aged 18–29: 8.7% of men and 6.7% of women had detectable plaque.
• Coronary calcium scans missed about half of coronary plaque in 30-to-39-year-olds with plaque because it was noncalcified.
• Coronary plaque was strongly linked to peripheral plaque: 82.0% of participants with coronary plaque also had peripheral artery plaque.
• The REACT study was cross-sectional, so age patterns are inferred from different age groups, not from following individuals over time.

What Is Silent Atherosclerosis and Why Does This Study Matter?

Atherosclerosis is the slow buildup of plaque—a mixture of cholesterol, fat, calcium, and inflammatory cells—inside the walls of arteries. Over time, plaque can narrow arteries, limit blood flow, or rupture and trigger a blood clot. That process underlies the world's leading causes of illness and death: coronary heart disease, ischemic stroke, peripheral artery disease, and sudden cardiac death.

When plaque accumulates without causing symptoms, doctors call it silent atherosclerosis. Many people live with it for decades before a heart attack or stroke is the first signal that anything was wrong. The word "silent" is what makes this condition so challenging.

Modern prevention strategies are largely driven by risk calculators that estimate a person's chance of having an event in the next decade. Those calculators use factors like age, blood pressure, and cholesterol. They do not show whether atherosclerosis is actually present, where it sits, or how much plaque has already formed.

This distinction matters because plaque is often present years before any risk calculator would flag a person as high risk. The REACT study, reported in the New England Journal of Medicine, was designed to answer a basic but crucial set of questions: When does silent atherosclerosis begin? How common is it at each stage of adult life? And where in the body does it first appear?

Background: What Researchers Already Knew

Imaging studies in older adults have consistently shown that silent atherosclerosis is common. Using techniques such as coronary-artery calcium scoring, coronary CT angiography (a special X-ray scan of the heart's arteries), and carotid or femoral ultrasound, previous studies detected silent atherosclerosis in roughly 40% to 80% of middle-aged and older participants.

Researchers have also established that a larger plaque burden is linked to higher risks of future cardiovascular events and death. Longitudinal imaging studies—studies that scan the same people over time—have shown that plaque burden can grow as years pass. Known modifiable risk factors appear particularly important to plaque progression in younger adults.

But a major gap remained. Most large imaging cohorts enrolled people who were already middle-aged or older. Studies that included adults under 40 were often small, limited to selected groups, or based on indirect markers rather than direct measurement of plaque. The result: no clear age- and sex-specific map showing when atherosclerosis first appears, how it spreads through different arteries, or how it accumulates from early adulthood through later life.

The REACT Initiative was created to fill that gap.

Study Methods: How the Research Was Conducted

REACT is a multicenter prospective cohort study carried out in Denmark and Spain. A prospective cohort study follows a defined group of people forward in time to observe how a condition develops. In this case, the researchers enrolled adults and performed detailed imaging at baseline to document the presence and amount of silent atherosclerosis.

The study was designed by academic investigators and conducted according to the Declaration of Helsinki, an international set of ethical principles for medical research. Ethics committees in both Denmark and Spain approved the protocol. Every participant gave written informed consent, and each person was told their own individual imaging results. The study funder, the Novo Nordisk Foundation, had no role in the design, data collection, analysis, or reporting.

Who was eligible? Adults aged 18 to 70 were eligible if they had no history of established clinical atherosclerotic cardiovascular disease—such as a prior heart attack, ischemic stroke, or peripheral artery disease—and no previous coronary revascularization (a procedure like a stent or bypass to restore blood flow to the heart). Symptoms such as chest pain from angina or leg pain from claudication were not formal reasons for exclusion, as long as no disease had been formally diagnosed.

How were participants chosen? The enrollment plan called for roughly 2,000 participants in each of the youngest (18 to 29) and oldest (60 to 70) age groups, and roughly 4,000 in each of the middle groups (30 to 39, 40 to 49, and 50 to 59). Within each stratum, researchers aimed for balanced numbers of men and women and balanced recruitment from each country.

The two countries used different recruitment methods. In Denmark, participants were identified through stratified random sampling from the Civil Registration System, a national database. In Spain, participants volunteered in response to open public advertisement. This difference in recruitment is worth keeping in mind when interpreting results.

What imaging was performed? Each participant underwent multimodal imaging of three arterial territories:

• Carotid arteries (the arteries in the neck that supply the brain), assessed with three-dimensional vascular ultrasound
• Femoral arteries (the arteries in the groin and upper legs), also assessed with three-dimensional vascular ultrasound
• Coronary arteries (the arteries on the surface of the heart that feed the heart muscle), assessed with coronary CT angiography

Coronary calcification—calcium deposits within plaque—was measured separately with noncontrast CT, and results were expressed as coronary-artery calcium scores in Agatston units, a standard measurement scale.

Researchers also estimated traditional cardiovascular risk with the SCORE2 framework (Systematic Coronary Risk Evaluation 2). SCORE2 predicts a person's 10-year risk of fatal and nonfatal cardiovascular disease for European adults aged 40 to 69. Higher scores indicate higher risk.

For statistical analysis, prevalence was calculated as the percentage of participants with at least one plaque in any examined territory. Age trajectories were estimated with cubic spline curves, a flexible statistical method that captures how a trend changes across age. Models were adjusted for country, sex, and age as appropriate. Results were reported as adjusted odds ratios with 95% confidence intervals (CI).

The researchers note that they made no statistical adjustment for multiplicity—that is, for the fact that many comparisons were made. The unadjusted confidence intervals should therefore be read as descriptive rather than as formal tests of hypotheses.

Who Took Part in the Study

Between November 2024 and June 2026, the study enrolled 16,808 adults. Just over half, 50.3%, were recruited in Spain, and 49.7% in Denmark. The mean age was 45 years, with a standard deviation of 12 years, and 51.4% of participants were women.

Imaging results were available for most participants: carotid imaging in 16,317 people, femoral imaging in 15,844, and coronary imaging in 14,140. Complete imaging of all three territories was obtained in 13,186 participants, and this group formed the primary analysis population for prevalence estimates.

A broad range of clinical and laboratory measurements was collected at baseline, including blood pressure, lipid panels (cholesterol and triglycerides), body-mass index, glucose and HbA1c levels, C-reactive protein, smoking history, medication use, and family history of cardiovascular disease. The study population appeared representative of the general populations of Spain and Denmark.

Key Finding: More Than Half of Adults Have Silent Atherosclerosis

The headline result is striking. Among participants with complete imaging, 57.1% had silent atherosclerosis in at least one vascular territory (95% confidence interval, 56.3% to 58.0%).

The condition was significantly more common in men than in women:

• Men: 63.4% had plaque (95% CI, 62.2% to 64.6%)
• Women: 50.9% had plaque (95% CI, 49.7% to 52.1%)

After adjusting for age and other factors, women had an odds ratio of 0.44 for having silent atherosclerosis compared with men (95% CI, 0.40 to 0.48). In plain language: a woman's odds of having plaque were roughly 56% lower than a man's odds at the same age.

Silent atherosclerosis was already detectable in the youngest adults. In the 18-to-29 age group:

• 8.7% of men had plaque (95% CI, 6.7% to 11.1%)
• 6.7% of women had plaque (95% CI, 5.1% to 8.7%)

By ages 30 to 39, the numbers climbed steeply:

• 34.6% of men had plaque (95% CI, 32.2% to 37.0%)
• 21.3% of women had plaque (95% CI, 19.2% to 23.5%)

The odds of having silent atherosclerosis rose dramatically with each decade of life. For every 10-year increase in age, the adjusted odds ratio was 4.52 for men (95% CI, 4.21 to 4.87) and 3.85 for women (95% CI, 3.61 to 4.12). This exponential pattern means that risk does not climb evenly year by year—it accelerates.

By the time participants reached ages 60 to 70, having no plaque at all was the exception rather than the rule. Only 1.9% of men (95% CI, 1.1% to 3.0%) and 8.1% of women (95% CI, 6.4% to 10.0%) had no detectable plaque in any examined territory.

Men and Women Follow Different Timelines

The study revealed important differences in how atherosclerosis develops in each sex.

In men, prevalence began to climb noticeably starting in the 30-to-39 decade, and the curve started to flatten by midlife. In women, the steepest rise came later—after age 40. This delayed acceleration in women narrowed the gap between the sexes as age increased.

By ages 60 to 70, the difference between men and women had substantially closed, although women were still more likely than men to have completely clean arteries (8.1% versus 1.9%).

These patterns suggest that the biology of atherosclerosis, and probably the influence of hormonal changes around menopause, shifts the risk timeline for women. The results also emphasize that screening and prevention strategies cannot treat men and women as identical when it comes to vascular aging.

Where Plaque Collects: Neck, Legs, and Heart Arteries

The REACT study offers a detailed picture of how plaque distributes across the body's major arterial territories.

Young people usually have peripheral disease. Among younger participants, silent atherosclerosis was most often found in the peripheral arteries—the carotid and femoral arteries—rather than in the coronary arteries that supply the heart. When plaque was present in younger adults, it was usually confined to a single vascular territory and most often detected in the carotid arteries.

Combined territory involvement grows with age. In older age groups, plaque in both the carotid and femoral arteries became more common, particularly in men. Atherosclerosis is not a disease that stays put; it tends to spread across arterial beds over time.

Isolated coronary atherosclerosis was uncommon at every age. Plaque found only in the heart's arteries, with no plaque in the peripheral vessels, was rare in all age groups. It peaked at 9.3% of men (95% CI, 7.9% to 10.8%) and 5.0% of women (95% CI, 4.0% to 6.1%). This is a clinically useful finding: when atherosclerosis is present in the coronary arteries, it is very often accompanied by disease elsewhere in the vascular tree.

Coronary plaque severity and calcification both increased with age in men and women. But an important nuance emerged for younger adults: coronary plaque was frequently present even when no calcium could be detected on CT scanning. Among participants aged 30 to 39 who had coronary plaque, 41.8% of men (95% CI, 32.5% to 51.6%) and 48.4% of women (95% CI, 30.2% to 66.9%) had a coronary-artery calcium score of zero. This percentage declined with age, but noncalcified plaque was still observed in some adults aged 60 to 70.

That finding matters because coronary calcium scoring alone—a common screening test—would have missed roughly half of the coronary plaque in younger adults. Noncalcified (soft) plaque can still rupture and cause heart attacks, even though it is invisible to a calcium-only scan.

Atherosclerosis in different territories was strongly interrelated. Among participants who had coronary-artery plaque, 82.0% (95% CI, 80.7% to 83.2%) also had peripheral artery plaque. Among those without coronary plaque, only 41.5% (95% CI, 40.5% to 42.5%) had peripheral plaque.

The probability of having coronary atherosclerosis also rose steadily as peripheral plaque volume increased. Compared with the lowest quartile of peripheral plaque volume, participants in progressively higher quartiles had odds ratios of 1.32, 1.85, and 3.70 for coronary atherosclerosis. In other words, the more plaque seen in the neck and leg arteries, the higher the chance that plaque also exists in the heart's arteries.

What This Means for Patients and Doctors

The study's findings carry several practical messages.

Silent atherosclerosis is not an old person's disease. One in 11 men in their twenties already had plaque. Among people in their thirties, the figure was roughly one in three men and one in five women. Waiting until traditional risk scores suggest danger may mean waiting too long.

Risk calculators have blind spots. The study assessed how well conventional risk assessment identifies people with established silent atherosclerosis. It showed that a substantial burden of atherosclerosis exists in people whose traditional risk profiles might not prompt aggressive prevention. Importantly, the presence of silent atherosclerosis is associated with cardiovascular events and death independently of traditional risk factors, based on earlier research cited by the authors.

Peripheral arteries offer a window into the heart. Because isolated coronary atherosclerosis was uncommon, and because coronary plaque was strongly linked to peripheral plaque volume, ultrasound of the carotid and femoral arteries may serve as an accessible first step for detecting systemic atherosclerosis. Ultrasound does not involve radiation and is widely available.

Calcium scans can miss early disease. The high rate of noncalcified coronary plaque in younger adults suggests that a zero calcium score does not guarantee clean coronary arteries in that population. This is particularly relevant if calcium screening is being considered for adults under 40 or 45.

Prevention should be sex-aware. The later but steep rise in women suggests that regular risk assessment during the 40s and 50s is critical for women, even if earlier scans or risk scores were reassuring.

Study Limitations: What This Research Could Not Show

The REACT study is the largest of its kind, but it has limits that should be acknowledged.

Cross-sectional design. All imaging and measurements were taken at a single time point. The study describes plaque prevalence at different ages, but it does not directly follow individuals over time. The age patterns are inferred by comparing different groups of people, not by watching the same people age. True progression rates require longitudinal follow-up, which the REACT team may provide in future reports.

Country-specific recruitment differences. Danish participants were selected by random sampling from a national registry, while Spanish participants self-selected through public advertisement. Volunteers who respond to advertisements may be healthier or more health-conscious than the general population, which could affect prevalence estimates. The authors note the population appeared representative, but some selection bias is possible.

Statistical considerations. Confidence intervals were not adjusted for the multiple comparisons made in the study. The authors explicitly state that the intervals should be interpreted as descriptive, not as replacements for formal hypothesis testing.

Incomplete imaging in some participants. Coronary imaging was available in 14,140 of the 16,808 enrolled participants, and complete three-territory imaging in 13,186. If the participants missing imaging differed systematically from those with complete imaging, prevalence estimates could be slightly affected.

Definitions of "no plaque." The finding that only 1.9% of men aged 60 to 70 had no plaque depends on the sensitivity of the imaging techniques used. It is possible that very small plaques below the detection threshold of ultrasound or CT were present but not counted.

What the study does not prove. The study shows that plaque is present; it does not directly measure which participants will go on to have heart attacks or strokes. Atherosclerosis is a necessary precursor to many events, but not every plaque causes an event, and the study does not yet provide event-based outcomes for these participants.

Recommendations for Patients

Based on the REACT findings and the broader medical literature, patients can take practical steps:

1. Do not assume young and healthy means no plaque. The study found atherosclerosis in 8.7% of men and 6.7% of women in their twenties. Healthy lifestyles matter early, not just after a diagnosis.
2. Know your numbers, but understand their limits. Blood pressure, cholesterol, blood sugar, and standard risk scores are essential tools, but the REACT study shows that a reassuring risk score does not rule out silent atherosclerosis.
3. Ask your doctor about vascular imaging if you have accumulated risk factors. The study found a strong link between peripheral plaque and coronary plaque. Carotid or femoral ultrasound, which is noninvasive and radiation-free, can reveal whether atherosclerosis is present years before a cardiac event.
4. Do not rely on a calcium scan alone if you are under 40. Among 30-to-39-year-olds with coronary plaque, roughly 42% to 48% had a coronary calcium score of zero. Noncalcified plaque is invisible to calcium-only screening. CT angiography with contrast, when clinically indicated, can detect both calcified and noncalcified plaque.
5. Women need continued vigilance after 40. The steepest rise in silent atherosclerosis for women occurred after age 40. A normal assessment in your thirties is not a reason to skip reassessment in your forties and fifties.
6. Treat modifiable risk factors seriously. The authors cite extensive prior evidence that modifiable risk factors—smoking, blood pressure, cholesterol, diabetes—drive plaque progression, particularly in younger people. Lowering those factors is the most direct way to slow or stop the disease that was so common in this study.
7. If you already know you have plaque, view it as an opportunity. Silent atherosclerosis is a warning, but it is also a chance to act before symptoms or events occur. The very fact that this disease is detectable years in advance is what makes prevention possible.

Future reports from the REACT cohort, which follows participants over time, will help answer the next critical question: which patterns of silent atherosclerosis most strongly predict actual heart attacks, strokes, and death?

Frequently Asked Questions

What does it mean if I have 'silent atherosclerosis' and no symptoms?

It means fatty plaque has built up inside your artery walls without causing symptoms. Over time, plaque can narrow arteries or rupture and trigger a heart attack or stroke. The REACT study found silent atherosclerosis in 57.1% of 13,186 adults with no known heart or vascular disease. It is detectable years before symptoms appear.

What does a coronary-artery calcium score of zero mean? Can I still have plaque?

A calcium score of zero means no calcified plaque was detected, but it does not rule out noncalcified soft plaque. In the REACT study, among 30-to-39-year-olds with coronary plaque, 41.8% of men and 48.4% of women had a calcium score of zero. This soft plaque can still rupture and cause heart attacks.

I am a woman over 40. Am I at risk for silent atherosclerosis even if my risk scores look normal?

Yes. Women in the REACT study showed a steep rise in silent atherosclerosis after age 40. Overall, 50.9% of women had plaque compared with 63.4% of men. However, by ages 60–70, 8.1% of women still had clean arteries versus 1.9% of men. Women should not assume a normal assessment in their 30s means continued safety.

How is silent atherosclerosis detected? What about ultrasound of the neck or leg arteries?

The REACT study used three-dimensional vascular ultrasound of carotid and femoral arteries plus coronary CT angiography. Because isolated coronary plaque was uncommon and coronary plaque strongly linked to peripheral plaque, ultrasound of neck and leg arteries may serve as a first step. It is noninvasive, radiation-free, and widely available.

What practical steps should I take based on the REACT study findings?

Do not assume being young means no plaque. Know your blood pressure, cholesterol, blood sugar, and standard risk scores, but understand a reassuring score does not rule out silent atherosclerosis. Ask your doctor about vascular imaging if you have accumulated risk factors. Treat modifiable risk factors seriously, and if you have plaque, view it as an opportunity to act before symptoms occur.

I was just diagnosed with silent atherosclerosis on an ultrasound or CT scan. Should I get a second opinion?

Silent atherosclerosis is plaque without symptoms, and it is common: 57.1% of adults in the REACT study had it, including some people in their twenties. A second opinion is useful when your traditional risk score seems reassuring, because substantial plaque can exist despite normal risk profiles. If you are under 40, a calcium score of zero does not rule out noncalcified plaque; roughly 42–48% of 30-to-39-year-olds with coronary plaque had zero calcium. A second opinion can confirm the imaging finding and clarify whether additional testing or closer follow-up is warranted. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

This patient-friendly article is based on peer-reviewed research published in the New England Journal of Medicine.

Original title: Prevalence of Silent Atherosclerosis across Adult Life

Authors: H. Bundgaard, I. García-Lunar, K.F. Kofoed, R. Hasselbalch, C.N. Pérez-García, J.B. Kunkel, F.F. Stæger, F. Sánchez-Cabo, J.J. Fuster, V. Mass, J. Sánchez-González, M.V. Kragh, A.K. Ringgaard, J. Valls-Monzó, M.H.C. Pham, A. Devesa, M. Sejer, P. Sigvardsen, A. Quesada, C. Eberhard, A. García-Álvarez, L.M. Pehrson, Á. Navarro-Guzmán, S. Winther, M. Sørgaard, M. Gámez, M. Lundsgaard, C. Pérez-Herreras, R. Frikke-Schmidt, P.L. Sánchez, N. Eldrup, J. Torres-Macho, M. Bøttcher, V. Fuster, K.K. Iversen, and B. Ibanez, for the REACT Investigators

Publication details: Published August 29, 2026, at NEJM.org. DOI: 10.1056/NEJMoa2609059. Copyright © 2026 Massachusetts Medical Society.

Funding: Novo Nordisk Foundation. ClinicalTrials.gov number: NCT06692127.

This translation preserves all numerical data, confidence intervals, and study findings from the original article. For medical decisions, consult a qualified healthcare professional and review the original publication.