New research suggests that changes in specific immune cells may help identify people at greater risk of developing artery-clogging plaques, even before symptoms appear.

Atherosclerosis, the buildup of fatty plaques inside arteries, is one of the leading causes of heart attacks and strokes. While the condition becomes increasingly common with age, researchers are discovering that people do not all develop atherosclerosis at the same rate.

A new study suggests that part of the explanation may lie in the immune system.

The research, titled “CD8+ effector memory and regulatory T cell dynamics predict subclinical atherosclerotic plaque formation in healthy aging,” points to specific patterns of immune-cell activity that may be associated with the early development of atherosclerotic plaques.

Looking beyond cholesterol

For decades, cholesterol, particularly LDL cholesterol, has been a major focus of efforts to prevent cardiovascular disease. Lowering LDL can reduce the risk of heart attack and stroke, but it does not completely eliminate that risk. Some people develop significant atherosclerosis despite having relatively normal LDL levels.

This has led researchers to look more closely at other biological processes that influence how quickly plaques form and progress.

Inflammation is one important piece of the puzzle.

Atherosclerosis is not simply a matter of cholesterol accumulating inside an artery. The immune system plays a central role in the process. Macrophages, a type of immune cell, normally help remove excess cholesterol and repair damaged tissue within artery walls. But when they become overwhelmed by cholesterol and other lipids, they can become dysfunctional, die, and contribute to the formation of an unstable plaque.

Other immune cells can also influence what happens inside an artery. Among them are T cells, which help coordinate and regulate immune responses.

Immune cells may offer an early warning. The new findings focus on two types of T cells: CD8+ effector memory T cells and regulatory T cells.

Rather than simply measuring how much plaque is already present, researchers investigated whether changes in these immune-cell populations could help predict the formation of subclinical atherosclerosis, plaque that has developed without causing obvious symptoms.

This is potentially important because atherosclerosis can remain hidden for years. By the time a person experiences a heart attack or stroke, substantial disease may already be present.

Current imaging technologies can detect atherosclerotic plaque, but identifying very early disease remains challenging. A reliable biological marker that could signal increased risk before significant plaque develops could therefore provide a valuable new tool for prevention.

A complex disease with many contributors

Atherosclerosis is influenced by numerous factors, including age, chronic inflammation, excess body weight, metabolic dysfunction, genetics and several types of blood lipids. Researchers are also uncovering less familiar contributors, such as lipoprotein(a), or Lp(a), which can increase cardiovascular risk independently of traditional cholesterol measures.

The immune system may provide another important piece of this increasingly complex picture.

The study does not mean that immune-cell patterns can yet be used as a routine clinical test to predict who will develop atherosclerosis. Instead, it adds to growing evidence that the immune system and cardiovascular health are closely connected.

Toward earlier detection and more personalized prevention

Understanding why some people develop plaques faster than others could eventually lead to better ways of identifying high-risk individuals before disease becomes clinically apparent.

It could also open the door to treatments that target mechanisms involved in inflammation and immune-cell dysfunction, alongside established approaches such as cholesterol management, blood-pressure control, healthy diet, exercise and smoking cessation.

For now, the findings reinforce a broader lesson emerging from cardiovascular research: atherosclerosis is more than a cholesterol problem. It is a complex interaction between lipids, metabolism, inflammation and the immune system.

As researchers learn more about these interactions, immune-system signatures could become part of a future toolkit for detecting cardiovascular risk earlier, and potentially preventing dangerous plaques before they cause a heart attack or stroke.