A study published today in Circulation: Cardiovascular Imaging found that women may face heart attack risk at lower levels of artery-clogging plaque than men, challenging the long-held assumption that women are less vulnerable to heart disease due to having less plaque. The research, which analyzed health data from over 4,200 adults, showed that despite having less plaque, women were just as likely as men to die from any cause, have a non-fatal heart attack, or be hospitalized for chest pain.
According to the study, fewer women had plaque in their coronary arteries compared to men (55% versus 75%), and the volume of plaque was lower in women (median 78 mm3 versus 156 mm3). However, the risk of major heart conditions began to increase in women at a plaque burden of 20%, while men's risk started at 28%. Moreover, as plaque levels increased, the risk rose more sharply for women than for men.
“Our findings underscore that women are not ‘protected’ from coronary events despite having lower plaque volumes,” said senior author Dr. Borek Foldyna, an assistant professor in radiology at Harvard Medical School. “Because women have smaller coronary arteries, a small amount of plaque can have a bigger impact. 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 study included participants from the PROMISE trial, which involved adults with stable chest pain and no prior history of coronary artery disease. Participants were randomized to undergo diagnostic evaluation via coronary computed tomography angiography and were followed for about two years. The findings highlight the need for sex-specific risk assessment in cardiovascular disease.
According to the American Heart Association’s 2026 Heart Disease and Stroke Statistics, cardiovascular disease was the cause of death in 433,254 females of all ages, representing 47.3% of deaths from cardiovascular disease. Dr. Stacey E. Rosen, volunteer president of the American Heart Association, emphasized the importance of recognizing sex differences in heart disease: “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, a research fellow at Massachusetts General Hospital and Harvard Medical School. The research was published in the American Heart Association’s journal Circulation: Cardiovascular Imaging. Additional information about the study can be found in the manuscript.
These findings have significant implications for clinical practice, suggesting that current thresholds for defining high plaque burden may need to be adjusted for women. As heart disease remains the leading cause of death in the U.S., understanding these differences is crucial for improving outcomes in all patients.
