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

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Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk. / Musunuru, Kiran; Orho-Melander, Marju; Caulfield, Michael P; Li, Shuguang; Salameh, Wael A; Reitz, Richard E; Berglund, Göran; Hedblad, Bo; Engström, Gunnar; Williams, Paul T; Kathiresan, Sekar; Melander, Olle; Krauss, Ronald M.

In: Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 29, 2009, p. 1975-U628.

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Musunuru, Kiran ; Orho-Melander, Marju ; Caulfield, Michael P ; Li, Shuguang ; Salameh, Wael A ; Reitz, Richard E ; Berglund, Göran ; Hedblad, Bo ; Engström, Gunnar ; Williams, Paul T ; Kathiresan, Sekar ; Melander, Olle ; Krauss, Ronald M. / Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk. In: Arteriosclerosis, Thrombosis and Vascular Biology. 2009 ; Vol. 29. pp. 1975-U628.

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TY - JOUR

T1 - Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk.

AU - Musunuru, Kiran

AU - Orho-Melander, Marju

AU - Caulfield, Michael P

AU - Li, Shuguang

AU - Salameh, Wael A

AU - Reitz, Richard E

AU - Berglund, Göran

AU - Hedblad, Bo

AU - Engström, Gunnar

AU - Williams, Paul T

AU - Kathiresan, Sekar

AU - Melander, Olle

AU - Krauss, Ronald M

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1161/ATVBAHA.109.190405

DO - 10.1161/ATVBAHA.109.190405

M3 - Article

C2 - 19729614

VL - 29

SP - 1975-U628

JO - Arteriosclerosis, Thrombosis and Vascular Biology

JF - Arteriosclerosis, Thrombosis and Vascular Biology

SN - 1524-4636

ER -