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

Musunuru, Kiran; Orho-Melander, Marju LU ; Caulfield, Michael P; Li, Shuguang; Salameh, Wael A; Reitz, Richard E; Berglund, Göran LU ; Hedblad, Bo LU ; Engström, Gunnar LU and Williams, Paul T, et al. (2009) In Arteriosclerosis, Thrombosis and Vascular Biology 29. p.628-1975
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.... (More)
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. (Less)
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Contribution to journal
publication status
published
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in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
29
pages
628 - 1975
publisher
American Heart Association
external identifiers
  • wos:000270996300041
  • pmid:19729614
  • scopus:73949114559
ISSN
1524-4636
DOI
10.1161/ATVBAHA.109.190405
language
English
LU publication?
yes
id
794cb7f3-19d4-4f1b-b1ec-5d63dce9f2b9 (old id 1483825)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19729614?dopt=Abstract
date added to LUP
2009-10-05 16:00:18
date last changed
2017-09-17 08:04:58
@article{794cb7f3-19d4-4f1b-b1ec-5d63dce9f2b9,
  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.},
  author       = {Musunuru, Kiran and Orho-Melander, Marju and Caulfield, Michael P and Li, Shuguang and Salameh, Wael A and Reitz, Richard E and Berglund, Göran and Hedblad, Bo and Engström, Gunnar and Williams, Paul T and Kathiresan, Sekar and Melander, Olle and Krauss, Ronald M},
  issn         = {1524-4636},
  language     = {eng},
  pages        = {628--1975},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Ion Mobility Analysis of Lipoprotein Subfractions Identifies Three Independent Axes of Cardiovascular Risk.},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.109.190405},
  volume       = {29},
  year         = {2009},
}