Association of Quantitative Coronary Artery Calcium Density Subtype Volumes With Major Adverse Cardiovascular Events

Background: Growing evidence has demonstrated that low density coronary artery calcification (CAC) is associated with a higher risk of cardiovascular events. Objectives: We aim to explore the relationship between CAC volumes at predefined densities, assessed by CAC volume according to CAC Hounsfield unit (HU), and major adverse cardiac events (MACEs). Methods: We evaluated 3 patient groups with no prior coronary artery disease history who underwent an electrocardiogram-gated noncontrast computed tomography scan for CAC scanning (CAC group, n = 2,028) or as part of a cardiac imaging test: single-photon emission computed tomography (SPECT)-myocardial perfusion imaging (SPECT group, n = 2,782), and positron emission tomography (PET)-myocardial perfusion imaging (PET group, n = 2,366). CAC subtype volumes of low, intermediate, and high density based on HU cutoff (low: 130-199 HU, intermediate: 200-399 HU, and high: ≥400 HU). MACE included mortality, myocardial infarction, unstable angina, and late revascularization. Results: During a median 4.3 years (interquartile ranges: 2.6-12.8) follow-up duration, 1,033 MACE occurred (14.4%). In multivariable analysis, low-density CAC volume was independently predictive of MACE (log-transformed; CAC group: HR: 1.65; 95% CI: 1.05-2.60; SPECT group: HR: 1.41, 95% CI: 1.02-1.94; PET group: HR: 1.34, 95% CI: 1.11-1.61; P < 0.05), whereas intermediate and high-density volumes were not (P > 0.05). Density CAC volumes improved discrimination and reclassification among all 3 groups (CAC, SPECT, and PET groups: global chi-square improvement: 9.1, 16.1, and 16.6, respectively, P < 0.01; net reclassification index: 47.3, [95% CI: 33.2-61.4], 49.6 [95% CI: 36.8-62.4] and 15.4, [95% CI: 5.9-24.9], respectively, P < 0.01). Conclusions: Low-density HU volume was independently associated with an increased MACE risk and improved discrimination and reclassification over conventional approaches in a broad spectrum of individuals undergoing CAC scanning.