Coronary Artery Calcium and Long-Term Risk of Death, Myocardial Infarction, and Stroke: The Walter Reed Cohort Study

Objectives: This study aimed to assess the long-term risk of death and atherosclerotic cardiovascular disease (ASCVD) outcomes, including stroke, in a real-world cohort that underwent coronary artery calcium (CAC) scoring. Background: Large-scale, long-term studies assessing the independent relationship of CAC for prediction of ASCVD events, to include stroke, in young, low-risk patients are uncommon outside of the clinical trial setting. Methods: A total of 23,637 consecutive subjects without ASCVD who underwent CAC scoring from 1997 to 2009 were studied. Subjects were assessed for myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE) (e.g., MI, stroke, or cardiovascular death), and all-cause mortality. Outcomes were extracted from the Military Data Repository and the National Death Index and assessed using Cox proportional hazards models, controlling for baseline risk factors, atrial fibrillation, and competing mortality. Results: Patients (mean age 50.0 ± 8.5 years) were followed over a median of 11.4 years. The relative adjusted subhazard ratio (aSHR) for CAC 1 to 100, 101 to 400, and >400 was 2.2, 3.8, and 5.9 for MI; 1.2, 1.4, and 1.9 for stroke; 1.4, 2.0, and 2.8 for MACE; and 1.2, 1.5 and 2.1 for death (p < 0.0001). The addition of CAC score to risk factors significantly improved the prognostic accuracy for all outcomes by the likelihood ratio test. Area under the curve increased from 0.658 to 0.738 for MI, 0.703 to 0.704 for stroke, 0.685 to 0.705 for MACE, and 0.759 to 0.767 for mortality. Among subjects without traditional risk factors (n = 6,208; mean age 43.8 ± 4.4 years), the presence of any CAC (>0; n = 848) was associated with an increased risk of MACE (aSHR: 1.67; 95% confidence interval: 1.16 to 2.39). Conclusions: CAC scoring significantly improved long-term prognostic accuracy for MACE events and mortality, irrespective of age and risk factors. These results support CAC screening for improving individual ASCVD risk assessment and prevention in low-risk, young adults.