Objective:
Coronary artery calcium score (CAC) predicts cardiovascular (CV) risk independent of conventional risk profile. However, it remains unclear how clinical risk profile modifies CV outcomes among subjects with elevated CAC with and without lipid lowering therapy.
Methods:
We conducted a post hoc analysis of the treatment trial of the St. Francis Heart Study_double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg, vitamin C 1 g, and vitamin E 1,000 U daily, versus matching placebos in 993 asymptomatic individuals with CAC at or above the 80th percentile for age and gender. Primary CV outcomes included non-fatal MI or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. Among the placebo and treatment groups, we further stratified by eligibility for statin therapy based on current AHA guidelines yielding 4 subgroups: treated not eligible (+Rx/-E), placebo not eligible (-Rx/-E), treated eligible (+Rx/+E) and placebo eligible (-Rx/+E).
Results:
Mean age was 59±6 years. Those eligible were older (61±5 vs. 56±5 years) and more likely to be males (85% vs. 56%) than those not eligible. Median [IQR] CAC was higher in the eligible than not eligible groups (overall, p<0.0001), 199 [112-396] (+Rx/-E), 207 [114-416] (-Rx/-E), 490 [289-791] (+Rx/+E) and 484 [286-837] (-Rx/+E). After a median follow up of 4.8 years, 4.0%, 4.8%, 9.8% and 15.4% had a CV event in +Rx/-E, -Rx/-E, +Rx/+E and -Rx/+E, respectively. After adjusting for CV risk factors and CAC, hazard ratio (95% CI) was 1.1 (0.4-2.9), 3.3 (1.1-9.4) and 4.9 (1.7-14.0) for -Rx/-E, +Rx/+E and -Rx/+E, respectively compared to +Rx/-E. There was a significant interaction between CAC and eligibility for statin therapy for a CV outcome (p=0.05).
Conclusion:
Among subjects with elevated CAC, those eligible for statin therapy have higher CAC and overall greater risk for a CV outcome than those not eligible. While statin therapy lowers CV risk among those eligible, it does not significantly alter CV risk among those not eligible. There is a significant interaction between CAC and statin therapy eligibility for a CV outcome. Our findings suggest that clinical risk profile remains an important risk modifier for CV outcomes among those with elevated CAC.
Prognostic value of coronary artery calcium score, area, and density among individuals on statin therapy vs. non-users: The coronary artery calcium consortium