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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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
29
pages
628 - 1975
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000270996300041
  • pmid:19729614
  • scopus:73949114559
  • pmid:19729614
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
2016-04-04 07:06:17
date last changed
2024-01-11 23:52:58
@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    = {{Lippincott Williams & Wilkins}},
  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}},
  doi          = {{10.1161/ATVBAHA.109.190405}},
  volume       = {{29}},
  year         = {{2009}},
}