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

OBJECTIVE—To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. APPROACH AND RESULTS—Plasma sdLD...

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Published inArteriosclerosis, thrombosis, and vascular biology Vol. 34; no. 5; pp. 1069 - 1077
Main Authors Hoogeveen, Ron C, Gaubatz, John W, Sun, Wensheng, Dodge, Rhiannon C, Crosby, Jacy R, Jiang, Jennifer, Couper, David, Virani, Salim S, Kathiresan, Sekar, Boerwinkle, Eric, Ballantyne, Christie M
Format Journal Article
LanguageEnglish
Published United States American Heart Association, Inc 01.05.2014
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Summary:OBJECTIVE—To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. APPROACH AND RESULTS—Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non–diabetes mellitus (49.6 versus 42.3 mg/dL; P<0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21–1.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04–2.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors. CONCLUSIONS—sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.
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ISSN:1079-5642
1524-4636
DOI:10.1161/ATVBAHA.114.303284