There are limited data on the unique CVD, non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC≥1000), especially in comparison to rates observed in secondary prevention populations.
Our study population consisted of 6814 ethnically diverse individuals age 45-84 years, free of known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC≥1000 were compared to both CAC=0 and CAC 400-999 for CVD, non-CVD, and mortality outcomes using Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC, and compared to those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial.
Compared to CAC 400-999, those with CAC≥1000 (N=257) had greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm2), similar CAC density, and more extensive extra-coronary calcification. After full-adjustment, CAC≥1000 demonstrated a 4.71-(3.63-6.11), 7.57-(5.50-10.42), 4.86-(3.32-7.11), and 1.94-fold (1.57-2.41) increased risk for all CVD events, all CHD events, hard CHD events, and all-cause mortality, respectively, compared to CAC=0 and a 1.65-(1.25-2.16), 1.66-(1.22-2.25), 1.51-(1.03-2.23), and 1.34-fold (1.05-1.71) increased risk compared to CAC 400-999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC≥1000 was associated with a 1.95-(1.57-2.41) and 1.43-fold (1.12-1.83) increased risk for a first non-CVD event compared to CAC=0 and CAC 400-999, respectively. CAC=1000 corresponded to an annualized 3-point MACE rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3), and higher than lower risk FOURIER subgroups.
Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, and similar 3-point MACE rates as a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary vs. secondary prevention patients in guiding aggressive preventive pharmacotherapy.