Metabolic syndrome is associated with HDL and VLDL subclass composition: The Rancho Bernardo Study

Metabolic syndrome (MetS) is a cluster of risk factors including high triglycerides [transported in blood as VLDL (very low density lipoprotein)] and low HDL (high density lipoprotein) cholesterol. We conducted a cross-sectional study of a population-based cohort of 2146 men and postmenopausal women (mean age 71 years) not taking cholesterol-lowering medication to examine whether the lipoprotein subclass distribution of HDL and VLDL contributes to atherosclerotic risk in individuals with MetS. The association between MetS and NMR-derived HDL and VLDL subclasses was examined using sex-specific linear regression models adjusted for age, current smoking, physical exercise, alcohol, and postmenopausal estrogen therapy. Overall, 334 (16%) participants met 2005 ATP-III criteria for MetS. Of those with MetS, 46% met ATP-III criteria for pattern B dyslipidemia (elevated HDL and decreased TG) versus 2% of those without MetS. While total lipoprotein levels differed by sex, subclass distributions of HDL and VLDL were similar. Compared to those without MetS, individuals with MetS had a 30-40% proportional increase in small and intermediate HDL, a 50% proportional decrease in large HDL, and a 6-7% decrease in HDL particle size (all p<.001), as well as proportionally more large VLDL (33% versus 15%), less small VLDL (33% versus 16-18%), and a 16-18% increase in VLDL size (p<.001). An atherogenic lipoprotein subclass distribution may contribute to the increased cardiovascular risk associated with the MetS. Whether these factors add to the clinical utility of simple and inexpensive measurement of total HDL and triglyceride can only be determined by prospective studies with clinical outcomes.