Advanced Subclinical Atherosclerosis in Young Individuals and Risk of Mortality Over 30 Years

Importance Coronary artery calcium (CAC) scoring is a well-established tool for predicting cardiovascular risk, but its long-term prognostic value in young adults remains unclear. As early preventive intervention may yield substantial lifetime benefit, understanding long-term implications of elevated CAC in young adults is important for informing prevention strategies. Objective To investigate the long-term risk of all-cause, cardiovascular disease (CVD), and coronary heart disease (CHD) mortality associated with premature advanced subclinical atherosclerosis. Design, Setting, and Participants This cohort study used the CAC Consortium dataset, a retrospectively assembled cohort of referred individuals with clinically indicated CAC scans. Using multivariable regression models for time-to-event analysis, the association of CAC with all-cause, CVD, and CHD mortality was assessed, adjusting for age, sex, and traditional atherosclerotic CVD risk factors. Cumulative incidence was derived for these outcomes in 5-year increments up to 30 years using a mixed approach involving the Kaplan-Meier method and Weibull modeling. The proportion of deaths attributable to CVD and CHD across CAC groups was evaluated. Four institutions across the US provided patient-level data to assemble the CAC Consortium. Included in the analysis were adults aged 30 to 45 years from the CAC Consortium. They were followed up for a median of 22.6 years. Study data were analyzed from October 2025 to September 2026. Exposure Elevated CAC in adults aged 30 to 45 years, specifically CAC score greater than 90%. Main Outcomes and Measures Participants were followed up for underlying cause of mortality. Results Among 12 847 participants, the mean (SD) age was 40.5 (3.6) years, and 9922 (77.2%) were male; 9262 (72.1%) had CAC score of 0, 1626 (12.7%) had a CAC score between 75% to 90%, and 1703 (13.3%) had a CAC score greater than 90%. In total, there were 624 deaths (149 CVD and 81 CHD). Multivariable adjusted hazard ratios for CAC score greater than 90% vs CAC score of 0 were 1.87 (95% CI, 1.54-2.27), 2.60 (95% CI, 1.77-3.82), and 3.71 (95% CI, 2.24-6.16), for all-cause, CVD, and CHD mortality, respectively. Over 30 years, the group with a CAC score greater than 90% had significantly higher modeled risk of all-cause (12.9% vs 7.5%), CVD (4.5% vs 1.5%), and CHD (3.0% vs 0.6%) mortality, compared with the group with a CAC score of 0. Conclusions and Relevance Results of this cohort study suggest that young adults with a CAC score greater than 90% face significantly higher long-term risk of all-cause, CVD, and CHD mortality, suggesting potential implications for guiding the intensification of preventive intervention in this high-risk phenotype.