Silent Atherosclerosis Found in Adults Across Denmark and Spain

Sometimes, a health problem can arrive with the force of a thunderclap.

You may be getting on with life feeling as fit as a fiddle when, suddenly, illness appears from nowhere.

Certain conditions really do emerge abruptly. Others can develop unnoticed for years, or even decades, before producing further symptoms – with a concealed disease process already in progress, if only it could be detected.

Silent atherosclerosis can begin long before symptoms

Atherosclerosis is one such condition. This gradual accumulation of plaque within the arteries is the main cause of cardiovascular disease, and scientists have long understood that it may progress silently for years before symptoms arise.

What has remained uncertain is precisely how early this hidden process starts, and how widespread it is at different points in adult life.

A new investigation involving almost 17,000 adults in Denmark and Spain, headed by cardiologists Henning Bundgaard of Copenhagen University Hospital and Borja Ibáñez of the Spanish National Centre for Cardiovascular Research, has now highlighted the stealthy frequency of silent atherosclerosis.

Of the participants who received complete imaging, over 57 percent of those aged 18 to 70 showed evidence of atherosclerosis, although prevalence differed sharply by age and sex.

"Because silent atherosclerosis predicts ischemic events and death independent of traditional risk factors, detection in young adults may identify a population at increased long-term risk at a stage at which the benefit of risk-factor control seems greatest," writes the team in a paper published in the New England Journal of Medicine.

Cardiovascular diseases are the world's foremost cause of death, and atherosclerosis underlies a substantial part of that vast burden.

The condition develops as fats, cholesterol and other materials collect in artery walls, creating deposits called plaques. These plaques may enlarge over time and reduce the space available for blood to flow. Should a plaque rupture, it can also cause a blood clot, potentially resulting in a heart attack or stroke.

However, a heart attack or stroke is not where the process starts. Atherosclerosis may grow for decades without symptoms before it creates difficulties, while some individuals may never experience symptoms at all.

At present, prevention of cardiovascular disease mainly depends on calculating an individual's risk from factors including age, blood pressure, cholesterol and smoking.

Yet such calculations do not necessarily reveal whether atherosclerosis is already present.

REACT maps atherosclerosis across adult life

Bundgaard, Ibáñez and their colleagues therefore aimed to chart the unseen disease itself throughout adulthood.

Their study, known as REACT, enrolled 16,808 adults aged from 18 to 70 in Denmark and Spain. None had received a diagnosis of cardiovascular disease.

The team then used ultrasound to look for plaques in the carotid arteries in the neck and the femoral arteries in the legs. They also used CT angiography to inspect the coronary arteries that supply the heart.

For this research, silent atherosclerosis meant plaque detected in at least one of these three areas in a person with no known cardiovascular disease.

Complete imaging of all three territories was available for 13,186 participants, and the findings began to form a compelling picture.

Silent atherosclerosis was already found in roughly 1 in 13 of the youngest participants, those aged 18 to 29.

Its frequency then rose swiftly. In their 30s, more than one-third of men – 34.6 percent – had detectable plaque, versus 21.3 percent of women.

Men tended to develop this atherosclerotic pattern sooner, with the researchers estimating an advantage of about 5 to 10 years. Women experienced a later but sharper increase during middle age.

At ages 60 to 70, the pattern had almost entirely flipped compared with early adulthood: only 1.9 percent of men and 8.1 percent of women had no detectable plaque whatsoever.

Silent atherosclerosis did not merely become more frequent with advancing age; it also spread more extensively through participants' bodies.

For those in their 30s, plaques in two or three of the assessed territories were identified in only 6 percent of men and 2.6 percent of women. Among those aged 60 to 70, plaque was present in all three territories in 56.3 percent of men and 30.7 percent of women.

The distinction was not simply the number of affected arteries either. Plaque volume also rose markedly with age, in a pattern consistent with exponential growth.

"Until now, preventive decisions have been based on an estimate of risk, but we did not know whether the disease was already present," Bundgaard says in a statement.

"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."

Imaging results and conventional cardiovascular risk

The results also revealed a notable mismatch between the disease visible to researchers and the risk forecast by standard assessments.

When the researchers compared imaging findings with SCORE2, a commonly used measure of a patient's 10-year cardiovascular risk, many participants with detectable atherosclerosis were not classed as being at especially high risk.

For participants aged 40 to 69, whose SCORE2 could be calculated, its high-risk cut-off identified only 1.9 percent of people with silent atherosclerosis.

This gap between estimated risk and the presence of disease was most pronounced at younger ages.

That does not make conventional assessments worthless. Instead, the researchers suggest that imaging for silent atherosclerosis could potentially sit alongside current methods of assessing risk.

The findings do not yet imply that everyone ought to have routine imaging for atherosclerosis. This stage of REACT was intended to chart the condition's prevalence, rather than determine whether screening produces better health outcomes.

The researchers hope to address that question next. Subject to funding, REACT's second phase will involve a large randomised clinical trial examining whether imaging-guided prevention can slow or lessen atherosclerosis progression more effectively than existing practice.

"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," Ibáñez says.

"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."

The findings have been published in the New England Journal of Medicine.

This article was fact-checked by Michael Irving and edited by Michael Irving. Although we take pride in our process, we are only human. If you notice an error, please let us know.