title: Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk In Communities (ARIC) study.
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.
  
  
  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.
authors.affiliation: From the Department of Medicine, Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, Houston, TX (R.C.H., J.W.G., W.S., J.J., S.S.V., C.M.B.); Human Genetics Center, University of Texas Health Science Center School of Public Health, Houston (R.C.D., J.R.C., E.B.); Department of Biostatistics, University of North Carolina at Chapel Hill (D.C.); Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX (S.S.V.); Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.K.); and Department of Medicine, Harvard Medical School, Boston, MA (S.K.).
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.forename: John W
authors.initials: JW
authors.lastname: Gaubatz
authors.forename: Wensheng
authors.initials: W
authors.lastname: Sun
authors.forename: Rhiannon C
authors.initials: RC
authors.lastname: Dodge
authors.forename: Jacy R
authors.initials: JR
authors.lastname: Crosby
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jiang
authors.forename: David
authors.initials: D
authors.lastname: Couper
authors.forename: Salim S
authors.initials: SS
authors.lastname: Virani
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D015994:Incidence; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D010641:Phenotype; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013381:Subtilisins / Q000235:genetics; D013997:Time Factors; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; C099101:PCSK7 protein, human; D013381:Subtilisins
keywords: coronary disease; genome-wide association study; triglycerides