Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) study

Ron C. Hoogeveen, John W. Gaubatz, Wensheng Sun, Rhiannon C. Dodge, Jacy R. Crosby, Jennifer Jiang, David Couper, Salim S. Virani, Sekar Kathiresan, Eric Boerwinkle, Christie M. Ballantyne

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389 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1069-1077
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume34
Issue number5
DOIs
Publication statusPublished - May 2014
Externally publishedYes

Keywords

  • coronary disease
  • genome-wide association study
  • triglycerides

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