CT Improves Cardiovascular Risk Assessment in Women with Chest Pain
Quantifying plaque may help catch women with high risk who may be missed by traditional models
Plaque assessment with coronary CT angiography (CCTA) improves cardiovascular risk stratification in women with stable chest pain, with limited added value in men beyond traditional clinical and imaging measures.
Lead author Jan Brendel, MD, a postdoctoral research fellow at the Cardiovascular Imaging Research Center (CIRC) at Mass General Brigham in Boston, said the results support a role for plaque quantification with CCTA in identifying women at high-risk who may be missed by traditional models, enabling earlier diagnosis and tailored treatment.
Current cardiovascular risk assessment often underestimates risk in women. Traditional risk models and diagnostic approaches were developed largely in male populations and are not optimized for women. Women more commonly have nonobstructive or microvascular coronary disease and atypical symptoms, which can be missed by standard testing and lead to delayed diagnosis and treatment.
“In addition, heart attacks in women are more often due to causes other than plaque rupture, which may not be as easily predicted by angiography,” Dr. Brendel said. “Also, women are falsely perceived to be protected against heart disease, particularly before menopause, which may lead to reduced vigilance and less adequate treatment.”
Dr. Brendel shares insights on how CCTA plaque assessment improves cardiovascular risk prediction in women with stable chest pain.
CCTA is a non-invasive imaging test that quantifies plaque in coronary arteries and can distinguish between stable calcified plaque and the more dangerous noncalcified plaque. Its ability to stratify patients by risk can speed interventions, ultimately improving patient outcomes. Despite its effectiveness, little is known about its sex-specific risk prognostic value.
To learn more, Dr. Brendel and colleagues compared outcomes among women and men drawn from the CCTA arm of the PROspective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), funded by the National Institutes of Health (NIH). Of the 4,267 patients in the study, slightly more than half were women.
The researchers quantified plaque volume and burden and looked at major adverse cardiovascular events like heart attacks, angina and death over a median follow-up of 26 months.
Compared to men, women had substantially lower median plaque volume and plaque burden. Major adverse cardiovascular events occurred in 2.8% of the study group. In women, total and noncalcified plaque burden independently predicted major adverse cardiovascular events. In men, these associations were not significant.
Less Plaque, Higher Stakes for Women
“The results suggest that adding plaque burden to traditional risk models would improve prediction of major adverse cardiovascular events in women,” Dr. Brendel said.
“Using coronary CT angiography data from the PROMISE trial, we found that although women tested for suspected coronary artery disease generally have less coronary plaque than men, cardiovascular risk appears to emerge at lower levels of plaque burden in women,” he said. “Moderate increases in plaque burden may therefore carry disproportionate risk in women, suggesting that current thresholds defining high risk underestimate risk in women. Thus, CCTA-derived quantitative plaque measures should be interpreted in a sex-specific clinical context.”
More research is needed before recommending the broader use of CCTA based solely on risk factors or biomarkers. However, Dr. Brendel said the findings show that even modest plaque burden in women undergoing CCTA for stable chest pain should not be dismissed as benign.
“While our data is not directly supporting CCTA in asymptomatic women, NIH-funded studies are underway to determine the yield for plaque when screening is based on different factors, such as premature family history, genetic risk, or multiple risk factors,” he said.
The researchers did not compare pre- and post-menopausal women, as menopausal status was not collected in the PROMISE trial. However, women enrolled in PROMISE were aged 50 years or older and are therefore likely to have been predominantly postmenopausal.
“Hormonal loss after menopause is thought to accelerate atherosclerosis and influence plaque composition and vascular function, making it plausible that cardiovascular risk trajectories differ across the menopausal transition, and this represents an important area for future research,” Dr. Brendel said.
Dr. Brendel won the 2025 RSNA Trainee Research Prize for his study. He expressed gratitude for the mentorship and collaborative environment at CIRC at MGB and the Duke Clinical Research Institute that made the work possible.
“Receiving the RSNA Trainee Research Prize is incredibly meaningful to me,” he said. “Knowing that this research contributes to improving how we understand and care for women with heart disease makes this award particularly special and motivating.”
For More Information
Access the research article, “Risk in Women Emerges at Lower Coronary Plaque Burden Than in Men: PROMISE Trial.”
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