Risk profile and prognostic implications of premature advanced coronary atherosclerotic disease among young to early middle-aged adults: the coronary artery calcium consortium

Aims Premature advanced subclinical coronary atherosclerosis among young adults is an under-recognized and unique disease phenotype that has not been well characterized. Methods and results We used data from 44 047 participants with no prior CVD history (59.8% male) from the Coronary Artery Calcium (CAC) Consortium. We defined advanced disease as CAC >= 90th percentile for age, sex, and race and compared the risk factor profile of persons with advanced disease to those without CAC and those with CAC < 90th percentile. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we assessed the association of premature advanced disease with all-cause, cardiovascular, and coronary heart disease (CHD) mortality. Of 44 047 participants, 18 561 (42.2%) had CAC. Among those with CAC, 6680 (36.0%) had CAC >= 90th percentile. Notably, 76.4% of those with CAC >= 90th percentile had multivessel CAC compared with 40.6% of those with CAC < 90th percentile. After a mean follow-up of 12.5 +/- 3.6 years, the incidence per 1000 person-years of all-cause (2.93 vs. 1.85 vs. 1.11), cardiovascular (1.11 vs. 0.39 vs. 0.21), and CHD mortality (0.65 vs. 0.19 vs. 0.08) was highest in the advanced disease group compared with CAC < 90th percentile and the no CAC group. Persons with CAC >= 90th percentile had a higher multivariable-adjusted risk of all-cause [HR: 2.17 (1.83-2.57)], cardiovascular [sub-distribution hazard ratios (SHR): 3.89 (2.78-5.44)], and CHD mortality [SHR: 5.45 (3.38-8.78)], compared with those without CAC. In the subgroup analysis, there was no difference in mortality between men and women with advanced CAC. Conclusion Premature advanced atherosclerosis is a distinct clinical phenotype that strongly predicts all-cause and cause-specific mortality. Among persons with CAC at young age, those with scores >= 90th percentile have the highest risk of early death and should be identified in future guidelines as a focus for aggressive clinical prevention. The findings of our paper show that young and early middle-aged individuals who have high burden of calcifications in their coronary vessels compared with their age, sex, and race-matched counterparts, have higher risk of death from any cause and death from cardiovascular diseases. This implies that we should be more aggressive in our preventive efforts towards this group of young adults. [GRAPHICS] .