LDL subclass distribution is associated with coronary calcification in postmenopausal women
Major lipoprotein classes consist of particles of various sizes, densities and composition. Associations between lipoprotein subclasses and coronary calcification were evaluated in 287 healthy women, 8 years post-menopause (age 56.9 to 65.4, mean=61.7 y). Coronary calcification score (CCS) was measured by electron beam CT and lipoprotein subclasses were determined by NMR spectroscopy. The mean CCS was 53 (range 0-1175) but 54% of the women had zero scores. CCS was analyzed as categories (CCS: 0, 1-99, ≥100). Current smoking was strongly associated with greater CCS but age and SBP were not significantly associated. Higher CCS was associated with higher triglycerides, total cholesterol and LDL-C, by NMR or usual methods, and total HDL-C by usual methods at the same visit (p < 0.05 for all). Large HDL and total HDL-C by NMR were weakly but not linearly related to CCS. Higher CCS was associated with higher levels of all VLDL subclasses categorized as small, medium or large (p<0.01). Only the smallest LDL subclass (L1) was related to CCS (p<0.01). Mean LDL particle size was smaller for higher CCS category (21.1 vs. 20.7 nm, p<0.01, for CCS = 0 vs CCS > 100). The number of LDL particles was also strongly related to CCS (p<0.001). Ordinal logistic regression was used to determine whether the lipoprotein subclasses were predictive of CCS category after adjustment for age, SBP, current smoking, and usual measures of LDL-C, HDL-C and triglycerides. Women with LDL particle concentrations ≥ 1800 nmol/L or levels of large VLDL > 27 mg/dL were more likely to be in a higher CCS category than those without these risk factors (OR = 2.09, 95% CI: 1.18, 3.70; OR= 2.21, 95% CI: 1.19,4.10, respectively.) After adjustment, higher CCS was still related to higher levels of small LDL (L1), but not to mean (LDL) particle size. These relationships were confirmed using linear regression with log-transformed variables. In postmenopausal women the size and number of LDL particles may be better predictors of atherosclerosis than total LDL-C. The level of large VLDL triglyceride contributes to decreased LDL size and increased number of LDL particles at a given level of LDL-C, via CETP and hepatic lipase.