Less plaque, but not less risk: a female paradox in coronary artery disease

By Elodie Vaz | Published on March 6, 2026 | 3 min read


Cardiovascular diseases remain the leading cause of morbidity and mortality in the United States and worldwide. According to the American Heart Association’s 2026 statistics, they caused 433,254 deaths among women, accounting for 47.3% of all cardiovascular deaths.   Coronary artery disease is primarily driven by atherosclerosis, characterized by the accumulation of plaques within the coronary arteries, which can lead to chest pain, myocardial infarction, or death. As International Women’s Day approaches on Sunday, March 8, previous research has shown that women generally have a lower prevalence and smaller volume of coronary plaques than men. This observation has sometimes been interpreted as suggesting a lower risk at comparable levels of atherosclerotic burden. A study published on February 23, 2026, in Circulation: Cardiovascular Imaging challenges this assumption.   When “less obstructed” arteries do not protect   The authors sought to determine whether a lower atherosclerotic burden truly protects women from major cardiovascular events. The objective was to compare, for a given plaque burden, the risk of severe events in women and men presenting with stable chest pain and no prior history of coronary artery disease.   The analysis focused on a subgroup from the PROMISE trial, conducted across 193 clinical centers in the United States and Canada. In total, 4,267 adults (mean age 60 years; 51% women) were included. All participants presented with stable chest pain and had no documented history of coronary disease.   A female cardiovascular paradox   Participants were randomized to undergo diagnostic evaluation using coronary CT angiography, allowing the presence and volume of plaque to be quantified. Median follow-up was approximately two years. The primary endpoint was a composite of all-cause mortality, nonfatal myocardial infarction, and hospitalization for chest pain.   Smaller arteries, greater risk?   The prevalence of coronary plaque was significantly lower in women: 55% compared with 75% in men. Median plaque volume was also lower (78 mm³ versus 156 mm³).   However, this lower atherosclerotic burden did not translate into a proportionally lower clinical risk. The incidence of the composite endpoint was comparable between sexes: 2.3% in women versus 3.4% in men.   Most notably, analysis by total plaque burden revealed a shift in the threshold at which risk begins to rise. In women, risk started to increase at a total plaque burden of 20%, compared with 28% in men. Moreover, the increase in risk associated with plaque progression appeared more pronounced in women.   “Our findings highlight that women are not ‘protected’ from coronary events despite having lower plaque volumes. Because their coronary arteries are smaller, even a small amount of plaque can have a greater impact. Moderate increases in plaque burden appear to confer disproportionately higher risk in women, suggesting that traditional definitions of high risk may underestimate risk in women,” said Dr. Borek Foldyna, Assistant Professor of Radiology at Harvard Medical School and lead author of the study, in a press release.   Stacey E. Rosen, volunteer president of the American Heart Association and executive director of the Katz Institute for Women’s Health, added: “These findings once again illustrate the importance of recognizing that cardiovascular diseases can affect men and women very differently. It is high time we acknowledge the fundamental biological differences in how health conditions manifest in women and men, and these differences may influence everything from risk factors to symptoms and response to treatment. I am encouraged to see more research like this emerging, helping us find ways to reduce the burden of cardiovascular disease for everyone.”   Rethinking prevention in women   This study highlights a major clinical paradox: in women, a quantitatively lower atherosclerotic burden does not equate to a proportionally lower risk. Risk thresholds based on absolute plaque volumes may therefore underestimate female vulnerability. These findings suggest the need to reconsider coronary risk assessment models by incorporating sex-specific parameters, both anatomical and pathophysiological. As precision medicine becomes an increasingly central objective, adapting diagnostic and prognostic thresholds according to sex could represent a key step toward reducing cardiovascular mortality among women.  

Read next: Hypertension: a new threshold, a new challenge