Small Dense Low-Density Lipoprotein Cholesterol and Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis.

Abstract

Elevated small dense-LDL-cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcium (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. This study included 4672 individuals with directly-measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis (mean [SD] age: 61.9 [10.4] years; 52.5% women; 47.3% with baseline CAC [mean score >0]). We used multivariable general linear models and restricted cubic splines with goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios (OR [95% CI]) were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with presence of CAC, even after accounting for total LDL-C. Compared to the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3 and 4 had higher odds for the presence of baseline CAC (Quartile 2 OR: 1.24 [1.00, 1.53]; Quartile 3 OR: 1.51 [1.19, 1.93]; and Quartile 4 OR 1.59 [1.17, 2.16]). Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: p=0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: p=0.156). In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.