Clinical significance of zero coronary artery calcium in individuals with LDL cholesterol ≥ 190 mg/dL: The Multi-Ethnic Study of Atherosclerosis

Background and aims: Individuals with low-density lipoprotein cholesterol (LDL-C) >= 190 mg/dL are considered high-risk and current guidelines recommend initiating high-intensity statin therapy in this group. We sought to examine the predictive ability of zero CAC in this high-risk group. Methods: Multi-Ethnic Study of Atherosclerosis participants without clinical cardiovascular disease and baseline LDL-C >= 190 mg/dL were identified. Cardiovascular risk factors were compared between those with CAC = 0 and CAC > 0. Multivariable Poisson regression was used to identify predictors of CAC = 0. Association of CAC = 0 with incident cardiovascular events over a median follow-up of 13.2 years was examined using multivariable-adjusted Cox regression. Results: 246 individuals (mean age = 63 +/- 9.4 years; 42% male; 31% white; 37% CAC = 0) with LDL-C >= 190 mg/dL were identified (mean LDL-C = 215 +/- 27 mg/dL). Age < 65 years (RR = 2.17, 95%CI = 1.49-3.23), female sex (RR = 2.10, 95%CI = 1.42-3.10), and no diabetes (RR = 2.22, 95%CI = 1.18-4.17) were associated with CAC = 0. Individuals with CAC = 0 had a lower risk for future cardiovascular events (incidence rate per 1000 person-years = 4.7; 10-year risk = 3.7%; risk/year = 0.4%) than those with CAC > 0 (incidence rate per 1000 person-years = 26.4; 10-year risk = 20%; risk/year = 2.0%), adjusted HR 0.25 (95%CI = 0.10-0.66). Conclusions: Among persons with LDL-C >= 190 mg/dL, younger age, female sex, and the absence of diabetes were associated with CAC = 0. CAC = 0 was associated with a low risk of cardiovascular events, suggesting the utility of CAC assessment for stratifying risk in this high-risk group.