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Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1975-80. doi: 10.1161/ATVBAHA.109.190405. Epub 2009 Sep 3.

Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk.

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  • 1Center for Human Genetic Research, Cardiology Division, Massachusetts General Hospital, Boston, MA, USA.

Abstract

OBJECTIVE:

Whereas epidemiological studies show that levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) predict incident cardiovascular disease (CVD), there is limited evidence relating lipoprotein subfractions and composite measures of subfractions to risk for CVD in prospective cohort studies.

METHODS AND RESULTS:

We tested whether combinations of lipoprotein subfractions independently predict CVD in a prospective cohort of 4594 initially healthy men and women (the Malmö Diet and Cancer Study, mean follow-up 12.2 years, 377 incident cardiovascular events). Plasma lipoproteins and lipoprotein subfractions were measured at baseline with a novel high-resolution ion mobility technique. Principal component analysis (PCA) of subfraction concentrations identified 3 major independent (ie, zero correlation) components of CVD risk, one representing LDL-associated risk, a second representing HDL-associated protection, and the third representing a pattern of decreased large HDL, increased small/medium LDL, and increased triglycerides. The last corresponds to the previously described "atherogenic lipoprotein phenotype." Several genes that may underlie this phenotype-CETP, LIPC, GALNT2, MLXIPL, APOA1/A5, LPL-are suggested by SNPs associated with the combination of small/medium LDL and large HDL.

CONCLUSIONS:

PCA on lipoprotein subfractions yielded three independent components of CVD risk. Genetic analyses suggest these components represent independent mechanistic pathways for development of CVD.

PMID:
19729614
[PubMed - indexed for MEDLINE]
PMCID:
PMC2772123
Free PMC Article
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