April 14, 2026

13 min read

Add Us On GoogleAdd SciAm

The hidden cause of heart disease is inflammation

Immune system overreactions may be the true culprit of cardiac illness—and lifesaving drugs can calm them down

By Melinda Wenner Moyer edited by Josh Fischman

Maria Corte

Doctors have been drilled for decades on the four big risks for heart disease, which kills more Americans every year than any other illness. The fearsome foursome: hypertension, smoking, high levels of “bad” LDL cholesterol and type 2 diabetes. Yet for just as long cardiologists have seen patients who have none of these problems die from heart ailments. And the heart specialists haven’t had the slightest idea why.

Up to a quarter of the people admitted to hospitals for heart attacks don’t have any of these four risk factors. Mysteriously, these “low-risk” heart disease patients actually have the worst outcomes. A 2023 analysis found that hospitalized acute coronary patients without any of the four hazards were 57 percent more likely to die compared with those who had at least one.

If the big known risk factors miss one in four patients, they still predict trouble as expected for the remaining three. That’s a good record. But it also means that of the roughly 920,000 Americans who die of cardiovascular disease every year, about 230,000 of them will have done so for no understandable reason.

On supporting science journalism

If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.

This deadly puzzle has haunted cardiologist Paul Ridker for years. “I remember saying to myself that there must be some other fundamental determinant of heart disease,” says Ridker, who is director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital in Boston.

Dozens of studies and clinical trials later, Ridker thinks he has found the missing piece. His work, along with that of other researchers, now suggests that chronic inflammation—a prolonged and body-damaging state of immune system activation—may be the hidden factor that accelerates cardiovascular problems to a dangerous and deadly state. When cholesterol builds up in the arteries, it shape-shifts into a sharp and jagged form the body no longer recognizes, provoking the immune system to wage war against it and blood vessels. It is a battle with no winners, and the wreckage it leaves behind ends in heart attacks and strokes.

Initially treated with skepticism, this idea now is becoming widely accepted by other scientists. Heart disease is “a disease of inflammation,” says Kathryn Moore, director of the Cardiovascular Research Center at New York University’s Grossman School of Medicine. And in the fall of 2025 the American College of Cardiology recommended that health-care providers routinely screen patients for inflammatory proteins.

> If inflammation drives cardiovascular disease, then calming it might protect the organ beating in our chests.

The concept brings with it renewed hope for heart therapy. If inflammation drives cardiovascular disease, then calming it might protect the organ beating in our chests. In June 2023 the U.S. Food and Drug Administration approved a new use of an inexpensive, inflammation-reducing drug for an old disease—gout—to treat patients with heart disease. In a 2020 clinical trial, researchers showed this drug, colchicine, could reduce the risk of heart attacks, strokes, and other complications by a dramatic 31 percent. And this big decrease was mostly among patients already taking the standard cholesterol-lowering medications: statins.

But this treatment is not without controversy. Some recent studies of colchicine have not found protective effects, and many cardiologists are reluctant to use it. Ridker and other researchers are now testing different anti-inflammatory therapies with more precise modes of action. Although questions remain, many researchers believe this shift—seeing the vascular system not as a series of clogged pipes but as battlefields of inflammation—could transform public health and save millions of lives.

For many decades the dogma among doctors and scientists was that atherosclerosis—the buildup of fatty substances, including cholesterol, in the arteries—was a passive, almost mechanical process, an inevitable by-product of aging. “We were taught that the plaque buildup in arteries was sort of like rust in a pipe,” says Jean-Claude Tardif, a cardiologist who directs the Research Center at the Montreal Heart Institute.

Yet there had been hints over the centuries that inflammation might play an active role in the process. In the mid-1850s German pathologist Rudolf Virchow peered through