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Olle Melander

Principal investigator

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

Author

  • Kiran Musunuru
  • Marju Orho-Melander
  • Michael P Caulfield
  • Shuguang Li
  • Wael A Salameh
  • Richard E Reitz
  • Göran Berglund
  • Bo Hedblad
  • Gunnar Engström
  • Paul T Williams
  • Sekar Kathiresan
  • Olle Melander
  • Ronald M Krauss

Summary, in English

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.

Department/s

  • Department of Clinical Sciences, Malmö
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension

Publishing year

2009

Language

English

Pages

628-1975

Publication/Series

Arteriosclerosis, Thrombosis and Vascular Biology

Volume

29

Document type

Journal article

Publisher

Lippincott Williams & Wilkins

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Epidemiology
  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1524-4636