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Gender and the Extent of Coronary Atherosclerosis, Plaque Composition, and Clinical Outcomes in Acute Coronary Syndromes
Open accessAbstract
Objectives This study sought to assess the extent and composition of atherosclerosis contributing to acute coronary syndrome events in women compared with men. Background Pathological studies suggest that plaque composition and burden may differ by sex. It is unclear whether sex impacts the extent, characteristics, and potential vulnerability of coronary plaques. Methods A total of 697 patients (24% women) with acute coronary syndromes were enrolled in the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. Three-vessel multimodality intracoronary imaging (quantitative coronary angiography, grayscale, and radiofrequency intravascular ultrasound [IVUS]) was performed after treatment of the culprit lesion(s). Events during a median 3.4-year follow-up were ascribed to recurrent culprit versus untreated nonculprit lesions. The authors performed a post hoc, sex-based subgroup analysis. Results Women were older and had more comorbid disease than men. By angiography, women had a similar number of angiographic culprit (p = 0.53) but fewer nonculprit (p = 0.05) lesions, and fewer vessels with nonculprit lesions (p = 0.048) compared with men even after multivariable adjustment (p = 0.002). By IVUS, women had fewer nonculprit lesions (p = 0.002), but similar plaque burden (PB) per lesion (55.6% vs. 55.3%; p = 0.35), and female sex was not predictive of severe (> 70%) PB (p = 0.052). Plaque rupture was less common in women (6.6% vs. 16.3%; p = 0.002) even after adjusting for comorbidities (p = 0.004), as was the total necrotic core volume (p < 0.0001). The frequency of other plaque phenotypes was similar for men and women including pathological intimal thickening, thin-cap fibroatheromas (TCFA), and thick-cap fibroatheromas. Rates of major adverse cardiovascular events attributed to culprit and nonculprit lesions at 1-, 2-, and 3-year follow-up were not significantly different between men and women, although women were rehospitalized more frequently due to culprit lesion-related angina. For men, nonculprit lesion minimal lumen area ≤ 4.0 mm(2), PB ≥70%, and TCFA predicted nonculprit MACE at 3 years, whereas for women, only TCFA and PB were predictive. Conclusions The PROSPECT study validates that despite having more comorbid risk factors than men, women have less extensive coronary artery disease by both angiographic and IVUS measures, and that lesions in women compared with men have less plaque rupture, less necrotic core and calcium, similar plaque burden, and smaller lumens. TCFA may also be a stronger marker of plaque vulnerability in women than men.
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“Men were selected to optimize statistical power given the higher prevalence of CAD in men, particularly in the age group studied.35”
From Wearable-Derived Training Load and Coronary Atherosclerosis in Middle-Aged and Older Athletes and Physically Active Controls: A New Perspective From the Master@Heart Study (2026) · cites this paper as [35]
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Mitrani, L. R., Shaw, L. J., & Lin, F. Y.-H. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-10618-7.00005-3
Svedberg, N. L., An, W., Tan, S., & Jaffe, I. Z. (2026) · PLoS ONE · doi:10.1371/journal.pone.0360618
Getz, M. J., Cao, T., Aronoff, J. E., Jenkins, C. L., Ghafoor, S., Vazquez, J., Appel, N. T., Cummings, D. K., Hooper, P. L., Beheim, B., et al. (2026) · American Journal of Biological Anthropology · doi:10.1002/ajpa.70309
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Metadata
- Authors
- Lansky, A. J., Ng, V. G., Maehara, A., Weisz, G., Lerman, A., Mintz, G. S., De Bruyne, B., Farhat, N., Niess, G., Jankovic, I., Lazar, D., Xu, K., Fahy, M., Serruys, P. W., & Stone, G. W.
- Affiliations
- Yale University (US)
- Columbia University Irving Medical Center (US)
- Mayo Clinic (US)
- Presbyterian Hospital (US)
- Erasmus MC (NL)
- Corresponding author
- Lansky, Alexandra J.
- ORCID
- Venue
- JACC: Cardiovascular Imaging
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 5
- Issue
- 3
- Pages
- S62-S72
- ISSN
- 1876-7591 (ISSN-L)
- 1936-878X
- OpenAlex
- W2079106078
- Cited by
- 289
- References
- 39
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 24 · 2023: 17 · 2022: 16 · 2021: 25 · 2020: 31 · 2019: 18 · 2018: 24 · 2017: 13 · 2016: 38 · 2015: 19 · 2014: 9 · 2013: 17 · 2012: 17
- FWCI
- 20.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- JACC. Cardiovascular imaging (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Boston Scientific Corporation
- InfraRedx
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Coronary Interventions and Diagnostics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Keywords
- acute coronary syndrome, sex differences, coronary artery disease, plaque composition, plaque burden, plaque rupture, necrotic core, thin-cap fibroatheroma, non-culprit lesions, major adverse cardiovascular events, women, intravascular ultrasound, quantitative coronary angiography, culprit lesion, hospital readmission, angina pectoris, PROSPECT study
- MeSH terms
- Aged, Angina, Unstable, Coronary Artery Disease, Europe, Female, Fibrosis, Heart Arrest, Humans, Male, Middle Aged, Myocardial Infarction, Necrosis, Predictive Value of Tests, Prospective Studies, Risk Factors, Severity of Illness Index, Sex Factors, Time Factors, United States, Angioplasty, Balloon, Coronary, Multivariate Analysis, Chi-Square Distribution, Logistic Models, Proportional Hazards Models, Treatment Outcome, Coronary Angiography, Ultrasonography, Interventional, Risk Assessment, Coronary Stenosis, Kaplan-Meier Estimate, Acute Coronary Syndrome, Plaque, Atherosclerotic, Vascular Calcification
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