Coronary artery disease (CAD) is the most common cause of death globally. In CAD, plaques composed of cholesterol, fats, calcium and other compounds accumulate and create obstructions in the coronary vessels that supply blood to the heart. It is well-known that plaque differs between women and men, with women typically having a smaller total volume of plaque, but it is unknown how this difference impacts risk of major adverse cardiovascular events (MACE). Investigators from Mass General Brigham analyzed data from nearly 4,300 stable outpatients with chest pain and no known prior CAD and found that, although women had smaller plaque volumes and fewer plaques with high-risk characteristics, they experienced similar rates of MACE compared with men and showed differences in how plaque burden related to cardiovascular risk over time. Results are published in Circulation .
"Our findings suggest that applying uniform thresholds across sexes to determine whether patients' plaque measures put them at high risk for MACE may underestimate risk in women," said lead author Jan Brendel, of the Cardiovascular Imaging Research Center (CIRC) in the Mass General Brigham Department of Radiology. "Based on the apparent differences in risk trajectories between men and women, incorporating sex, and even age, into the interpretation of plaque metrics is an important next step toward more individualized risk assessment."
Investigators utilized data from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), which was conducted across 193 North American sites. Using cardiac computed tomography angiography (CCTA) images, the researchers measured total plaque volume and total plaque burden (TPB), which is the amount of plaque relative to the size of the blood vessel. They also characterized plaque subtypes, including stable plaques, which are harder and contain more calcium, and high-risk plaques, which are softer and contain more fat compounds.
After a median of 26 months, women's risk of MACE (death, heart attack or hospitalization for chest pain) was similar to men's. Although women had a lower median plaque volume than men, their vessel size-adjusted median TPB was similar. Importantly, risk of MACE emerged at a lower TPB in women: approximately 20% versus approximately 28% in men. Additionally, in women, risk of MACE increased more steeply at lower plaque burden levels, whereas in men, risk of MACE increased gradually, requiring larger amounts of plaque. The earlier, steeper risk of MACE in women persisted after adjusting for traditional risk factors, and other imaging findings including presence of high-risk plaques. These findings suggest that incorporating sex into the interpretation of coronary plaque metrics may help advance tailored approaches to cardiac risk stratification.
Authorship: Mass General Brigham authors include Jan M. Brendel, Júlia Karády, Márton Kolossváry, Nóra M. Kerkovits, Isabel L. Langenbach, Matthias Jung, Marcel C. Langenbach, Michael T. Lu and Borek Foldyna. Additional authors include Thomas Mayrhofer, Michelle D. Kelsey, Neha Pagidipati, Svati H. Shah, Maros Ferencik and Pamela S. Douglas.
Disclosures: Brendel is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (540505270); Kolossváry was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences and by the 2024-2.1.1 University Research Scholarship Program of the Ministry of Culture and Innovation from the National Research, Development and Innovation Fund of Hungary. Project number PD 147269 and Excellence 151118 have been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the PD_23 and Excellence_24 funding scheme; Langenbach is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (502109212); Jung is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (518480401). Kelsey reports consulting fees from HeartFlow Inc. and Bayer Inc. Ferencik reports consulting fees from Cleerly, HeartFlow, Elucid, and BioMarin, advisory board of Cleerly and Elucid, and stock options from Elucid. Lu reports funding to his institution from the American Heart Association, Amgen, AstraZeneca, Ionis, Johnson & Johnson Innovation, Kowa Pharmaceuticals America, MedImmune, National Academy of Medicine, National Heart, Lung, and Blood Institute, and Risk Management Foundation of the Harvard Medical Institutions outside the submitted work. Foldyna reports institutional research support from the National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, MedImmune, Cleerly and MedTrace, all outside the submitted work. The other authors report no conflicts.
Funding: This study was supported by National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute grants (1R01HL098236), (1R01HL098237), (1R01HL098305), (1R01HL170877-01) and (1R01HL146145-01A1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Paper cited: Brendel, JM., et al. "Risk in Women Emerges at Lower Coronary Plaque Burden Than in Men: PROMISE Trial" Circulation: Cardiovascular Imaging. DOI: 10.1161/CIRCIMAGING.125.019011
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