Heart disease remains the leading cause of death worldwide, yet the way it develops and presents can differ significantly between women and men. A newly published research article in Circulation: Cardiovascular Imaging sheds important light on these differences. The study, titled “Risk in Women Emerges at Lower Coronary Plaque Burden Than in Men: PROMISE Trial,” was originally published on February 23, 2026, and is based on data from the landmark PROMISE Trial.
The findings suggest that women may face an increased risk of major cardiovascular events at lower levels of coronary plaque burden compared with men. This discovery has major implications for how clinicians interpret cardiac imaging and assess risk in female patients.
Coronary artery disease develops when fatty deposits, known as plaque, accumulate within the walls of the coronary arteries. Over time, this buildup can restrict blood flow and increase the risk of heart attack, unstable angina, or death.
Traditionally, attention has focused on obstructive disease, meaning severe narrowing of the arteries. However, nonobstructive plaque also carries meaningful risk. Even when arteries are not severely narrowed, the presence and composition of plaque can predict future events.
Coronary computed tomography angiography, commonly referred to as CCTA, allows physicians to visualize plaque in detail. Beyond identifying whether plaque is present, modern software can measure:
The new analysis from the PROMISE trial evaluated whether increasing plaque measurements translate into cardiovascular risk in the same way for women and men.
The PROMISE Trial, short for Prospective Multicenter Imaging Study for Evaluation of Chest Pain, enrolled over 10,000 patients across North America. Participants were stable outpatients with chest pain and no known history of coronary artery disease.
For this specific study, researchers analyzed 4,267 patients who underwent CCTA. Of these, 2,199 were women and 2,068 were men. The average age was just over 60 years.
The primary outcome measured was major adverse cardiovascular events, abbreviated as MACE. This included:
Patients were followed for a median of 26 months.
Several important differences were observed at baseline:
Despite these differences, the actual rate of major cardiovascular events was relatively similar:
This similarity in outcomes becomes especially interesting when plaque measurements are examined more closely.
One of the most important distinctions in this research is between plaque volume and plaque burden.
Plaque volume measures the total amount of plaque in cubic millimeters. Men had significantly higher plaque volumes across nearly all categories, including calcified and noncalcified plaque.
However, plaque burden represents plaque relative to vessel size. Since women typically have smaller coronary arteries, plaque burden may be a more meaningful measure when comparing sexes.
Remarkably, total plaque burden was nearly identical between women and men, even though women had much lower absolute plaque volumes.
This suggests that relative plaque extent, rather than absolute plaque size, may better reflect cardiovascular risk across sexes.
The most striking finding from the study relates to how risk increases as plaque burden rises.
Using advanced statistical modeling, researchers evaluated how hazard ratios for major events changed across increasing plaque burden levels.
In women:
In men:
In other words, women experienced elevated cardiovascular risk at substantially lower plaque burden levels compared with men.
A similar pattern was seen for noncalcified plaque:
These nonlinear risk curves show that women’s cardiovascular risk may accelerate earlier and more sharply.
Several biological and anatomical factors may help explain these findings.
Women typically have smaller coronary vessels. A given plaque deposit may therefore occupy a larger percentage of the artery, impairing blood flow more significantly.
Women may exhibit more diffuse plaque spread rather than focal blockages. This can reduce the ability of the coronary system to compensate through collateral circulation.
After menopause, hormonal shifts can promote inflammation, endothelial dysfunction, and adverse lipid changes. These processes may accelerate plaque progression.
Men more often exhibit lipid rich and necrotic core plaques. Women may have more calcified or fibrous plaque. While calcified plaque is often considered stable, in smaller arteries it may still represent advanced disease.
Observational data have shown that women are sometimes less likely to receive aggressive preventive therapies. In this study, statin use was similar between sexes, despite higher dyslipidemia rates in women. This raises questions about potential undertreatment.
These findings challenge the idea that women are inherently protected against heart disease because they have less plaque volume.
The study supports several important clinical considerations:
Just as coronary calcium scoring uses percentiles to contextualize risk, plaque burden percentiles could help identify women at elevated risk earlier.
The research suggests that moderate plaque levels in women may warrant closer monitoring and potentially earlier intervention.
Modern cardiology is moving toward personalized risk assessment. This includes integrating imaging biomarkers, clinical risk scores, and individualized patient characteristics.
CCTA derived plaque quantification represents a powerful tool in this evolution. When interpreted through a sex specific lens, it may improve early identification of women at heightened risk.
Future research may explore:
Such research could refine prevention strategies and reduce cardiovascular disparities.
As with all research, certain limitations should be acknowledged:
Despite these limitations, the findings are robust and clinically meaningful.
This important study published in Circulation: Cardiovascular Imaging highlights a critical insight: women may develop clinically significant cardiovascular risk at lower levels of coronary plaque burden than men.
Although women tend to have less plaque volume overall, their risk appears to rise earlier and more steeply once plaque accumulates. Plaque burden, which accounts for vessel size, may be a more appropriate metric for cross sex comparison.
These findings reinforce the need for sex specific cardiovascular evaluation, earlier preventive strategies in women, and more refined imaging interpretation.
Heart disease does not affect women and men in identical ways. Recognizing these differences can save lives.
Brendel JM, Mayrhofer T, Karády J, Kolossváry M, Kerkovits NM, Langenbach IL, Jung M, et al. Risk in Women Emerges at Lower Coronary Plaque Burden Than in Men: PROMISE Trial. Circulation: Cardiovascular Imaging. Originally published February 23, 2026.
This blog article is intended for educational and informational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional regarding personal health concerns or before making medical decisions. The interpretation provided here summarizes published research and should not replace individualized clinical judgment.
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