Atherosclerosis has traditionally been viewed as a disease of older age, but fresh scientific findings are shattering this stereotype. Published in The New England Journal of Medicine, a major new international study (REACT) reveals that pathological vascular changes quietly begin in the body even among completely healthy and asymptomatic young people.
What REACT studied
The REACT-DETECT phase enrolled 16,808 adults aged 18 to 70 years in Denmark and Spain. Participants had no known history of myocardial infarction, ischemic stroke, peripheral artery disease, or previous coronary revascularization.
The researchers used three types of vascular imaging:
Three-dimensional ultrasound of the carotid arteries.
Three-dimensional ultrasound of the femoral arteries.
Coronary CT angiography, with additional noncontrast CT to assess coronary-artery calcium.
Of the full cohort, 13,186 participants had complete imaging of all three vascular territories and formed the primary prevalence analysis.
The study also collected cardiovascular risk factors, blood biomarkers, omics samples, and retinal images. Its main purpose was to describe where silent atherosclerosis is present across adult life and how its distribution differs between women and men.
The main findings
Among participants with complete three-territory imaging, plaque was found in 57.1%. The prevalence was higher in men than women overall:
63.4% in men.
50.9% in women.
Atherosclerosis was already detectable in the youngest age group:
8.7% of men aged 18 to 29 years.
6.7% of women aged 18 to 29 years.
By ages 60 to 70, plaque was detected in approximately 9 of 10 participants. The study reported that only 1.9% of men and 8.1% of women in this age group had no plaque in any examined territory.
These figures describe the presence of imaging-detected plaque, not the proportion of people who will develop symptomatic cardiovascular disease.
Differences between men and women
The age-related pattern was not identical in women and men.
In men, plaque prevalence began increasing earlier, and the overall atherosclerotic profile appeared approximately 5 to 10 years ahead of that seen in women. In women, the steepest increase occurred between approximately 40 and 60 years of age, broadly overlapping with the menopausal transition.
This finding is consistent with the established observation that cardiovascular risk changes with age and reproductive stage. However, because REACT was cross-sectional, it cannot prove that menopause itself caused the observed increase or establish the precise biological mechanisms involved.
Atherosclerosis is often systemic
The study found that atherosclerosis frequently involved more than one vascular territory.
Among participants with coronary plaque, 82.0% also had plaque in at least one peripheral territory—the carotid or femoral arteries—compared with 41.5% of participants without coronary plaque.
Isolated coronary plaque was uncommon. Peripheral plaque, particularly carotid plaque, was often detectable at younger ages, while disease involving multiple territories became more common with increasing age.
This finding may have practical implications for research and possibly future screening strategies. Carotid and femoral ultrasound are non-invasive and easier to perform than coronary CT angiography. However, ultrasound of one vascular territory does not identify all disease: 18% of participants with femoral plaque but no carotid plaque would have been classified differently if only the carotid arteries had been examined.
Coronary calcium is not the whole picture
An important finding was that coronary plaque could be present even when the coronary-artery calcium score was zero.
Among participants aged 30 to 39 years who had coronary plaque, approximately 42% of men and 48% of women had no detectable coronary calcium. This proportion declined with age but remained relevant across the age range.
Therefore, a calcium score of zero does not exclude all early coronary atherosclerosis, particularly in younger adults. Calcium scoring and coronary CT angiography provide different information: calcium scoring detects calcified plaque, whereas CT angiography can identify both calcified and noncalcified plaque.
This does not mean that coronary CT angiography should be routinely performed in healthy young people. It means that a zero calcium score should not be interpreted as proof that no coronary plaque exists.
