Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk.

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title = "Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk.",
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 Malm{\"o} 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.",
author = "Kiran Musunuru and Marju Orho-Melander and Caulfield, {Michael P} and Shuguang Li and Salameh, {Wael A} and Reitz, {Richard E} and G{\"o}ran Berglund and Bo Hedblad and Gunnar Engstr{\"o}m and Williams, {Paul T} and Sekar Kathiresan and Olle Melander and Krauss, {Ronald M}",
year = "2009",
doi = "10.1161/ATVBAHA.109.190405",
language = "English",
volume = "29",
pages = "1975--U628",
journal = "Arteriosclerosis, Thrombosis and Vascular Biology",
issn = "1524-4636",
publisher = "Lippincott Williams & Wilkins",