A study published today in Circulation: Cardiovascular Imaging, an American Heart Association journal, challenges the notion that women are protected from heart disease due to lower levels of artery-clogging plaque. The research, which analyzed data from over 4,200 adults, found that women were just as likely as men to suffer from heart attacks, chest pain, or die from any cause, even though they had significantly less plaque buildup.
The study included participants with stable chest pain and no prior history of coronary artery disease. About half were women. All underwent coronary computed tomography angiography to measure plaque volume. Results showed that only 55% of women had any plaque in their coronary arteries, compared to 75% of men. Women also had a median plaque volume of 78 mm³, half that of men (156 mm³). Despite these differences, the rate of major cardiovascular events—death, non-fatal heart attack, or hospitalization for chest pain—was similar: 2.3% for women versus 3.4% for men.
Notably, women’s risk began to rise at a plaque burden of 20%, while men’s risk started at 28%. As plaque increased, risk escalated more steeply for women. “Because women have smaller coronary arteries, a small amount of plaque can have a bigger impact,” said senior author Borek Foldyna, M.D., Ph.D., an assistant professor in radiology at Harvard Medical School. “Moderate increases in plaque burden appear to have disproportionate risk in women, suggesting that standard definitions of high risk may underestimate risk in women.”
The findings underscore sex-specific differences in cardiovascular disease, a leading cause of death for both men and women. According to the American Heart Association’s 2026 Heart Disease and Stroke Statistics, cardiovascular disease caused 433,254 deaths among women in the U.S., accounting for 47.3% of all cardiovascular deaths. Stacey E. Rosen, M.D., FAHA, volunteer president of the American Heart Association, commented: “There is an overdue recognition of fundamental, biological differences in the way health conditions manifest in women vs. men, and these differences can influence everything from risk factors to symptoms to treatment response.”
The study’s lead author is Dr. Jan Brendel, M.D., a research fellow at Massachusetts General Hospital and Harvard Medical School. The analysis was a subset of the PROMISE trial, which enrolled adults at 193 clinical sites in the U.S. and Canada. Participants were followed for about two years. The full manuscript is available online.
These results highlight the need for sex-specific risk assessment in heart disease. While plaque burden is a key predictor, the threshold for high risk may differ between men and women. Clinicians should consider that even moderate plaque buildup in women could signal elevated danger, especially after menopause when risk accelerates. The American Heart Association continues to advocate for research and awareness to address disparities in cardiovascular care.
