Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease The Atherosclerosis Risk in Communities (ARIC) Study

Low-density lipoprotein-cholesterol (LDL-C) is considered one of the most important risk factors for cardiovascular disease and remains the primary target for current cardiovascular risk reduction strategies. LDL particles are a heterogeneous population, and it has long been hy- pothesized that a subfraction of LDL, small dense LDL, possesses atherogenic potential. In the current study, we investigated the relationship between plasma levels of small dense LDL-C and risk of incident coronary heart disease in the biracial Atherosclerosis Risk in Communities (ARIC) study cohort. Elevated plasma small dense LDL-C levels were associated with increased risk of incident coronary heart disease, even in individuals considered to be at low cardiovascular risk based on their LDL-C levels. Using genome-wide association analyses, we dis- covered 1 novel locus, PCSK7, for which genetic variation was significantly associated with small dense LDL-C levels and other lipid traits. Together these findings provide new insights into the role of the PCSK7 gene in lipid metabolism and risk of cardiovascular disease.