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Sex differences in calcified plaque and long-term cardiovascular mortality: observations from the CAC Consortium
Leslee J Shaw1, James K Min2, Khurram Nasir3
1Emory University School of Medicine, 1462 Clifton Rd NE, Room 529, Atlanta, GA, USA.
Insights
Coronary artery calcium (CAC) measures reveal sex-specific differences in cardiovascular disease risk. Advanced CAC metrics, beyond the Agatston score, improve risk prediction in women and men.
Area of Science:
- Cardiovascular disease research
- Medical imaging and diagnostics
- Sex differences in health
Background:
- Pathologic evidence suggests unique sex-specific mechanisms contribute to acute cardiovascular events.
- Existing research on long-term cardiovascular risk in women compared to men, based on coronary artery calcium (CAC) measures, is incomplete.
Purpose of the Study:
- To investigate long-term cardiovascular mortality risk differences between women and men using comprehensive coronary artery calcium (CAC) measures.
- To evaluate the utility of various CAC metrics, including lesion number, vessel involvement, lesion size, volume, and plaque density, in predicting cardiovascular risk stratified by sex.
Main Methods:
- Analysis of data from 63,215 asymptomatic women and men in the multicentre CAC Consortium with a median follow-up of 12.6 years.
- Collection of Pooled Cohort Equation (PCE) risk scores, risk factor data, Agatston score, and detailed CAC measures (lesion number, vessels, size, volume, plaque density).
- Utilized Cox proportional hazard models to estimate cardiovascular mortality, calculating sex interactions.
Main Results:
- Women had lower average PCE risk scores but exhibited distinct CAC characteristics, including fewer calcified lesions and vessels, yet larger lesion size and higher plaque density compared to men.
- While long-term cardiovascular mortality was similar in women and men without detectable CAC, the presence of CAC was associated with a 1.3-fold higher hazard for cardiovascular death in women versus men.
- Advanced CAC metrics demonstrated significant sex differences in risk prediction: multivessel CAC, ≥5 lesions, and lesion size ≥15 mm³ showed substantially higher relative hazards for cardiovascular disease mortality in women compared to men. CAC density was predictive in men but not in women.
Conclusions:
- Coronary artery calcium (CAC) measures beyond the traditional Agatston score are crucial for understanding sex differences in atherosclerotic plaque.
- These advanced CAC metrics can refine cardiovascular risk detection and inform tailored preventive strategies for both women and men.
- Further research into sex-specific patterns of atherosclerosis using detailed CAC imaging is warranted.
Aims:
Pathologic evidence supports unique sex-specific mechanisms as precursors for acute cardiovascular (CV) events. Current evidence on long-term CV risk among women when compared with men based on measures of coronary artery calcium (CAC) remains incomplete.
Methods And Results:
A total of 63 215 asymptomatic women and men were enrolled in the multicentre, CAC Consortium with median follow-up of 12.6 years. Pooled cohort equation (PCE) risk scores and risk factor data were collected with the Agatston score and other CAC measures (number of lesions and vessels, lesion size, volume, and plaque density). Cox proportional hazard models were employed to estimate CV mortality (n = 919). Sex interactions were calculated. Women and men had average PCE risk scores of 5.8% and 9.1% (P < 0.001). Within CAC subgroups, women had fewer calcified lesions (P < 0.0001) and vessels (P = 0.017), greater lesion size (P < 0.0001), and higher plaque density (P = 0.013) when compared with men. For women and men without CAC, long-term CV mortality was similar (P = 0.67), whereas detectable CAC was associated with 1.3-higher hazard for CV death among women when compared with men (P < 0001). Cardiovascular mortality was higher among women with more extensive, numerous, or larger CAC lesions. The relative hazard for cardiovascular disease (CVD) mortality for women and men was 8.2 vs. 5.1 for multivessel CAC, 8.6 vs. 5.9 for ≥5 CAC lesions, and 8.5 vs. 4.4 for a lesion size ≥15 mm3, respectively. Additional explorations revealed that women with larger sized and more numerous CAC lesions had 2.2-fold higher CVD mortality (P < 0.0001) as compared to men. Moreover, CAC density was not predictive of CV mortality in women (P = 0.51) but was for men (P < 0.001), when controlling for CAC volume and cardiac risk factors.
Conclusion:
Our overall findings support that measures beyond the Agatston score provide important clues to sex differences in atherosclerotic plaque and may further refine risk detection and focus preventive strategies of care.
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