| Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk. | |
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MedLine Citation:
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PMID: 19729614 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-09-03 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 29 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-22 Completed Date: 2010-02-04 Revised Date: 2010-12-03 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1975-80 Citation Subset: IM |
Affiliation:
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Center for Human Genetic Research, Cardiology Division, Massachusetts General Hospital, Boston, MA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Biological Markers / blood Cardiovascular Diseases / blood* Cholesterol, HDL / blood* Cholesterol, LDL / blood* Chromatography, High Pressure Liquid Chromatography, Ion Exchange Cohort Studies Female Humans Ion Transport Lipoproteins, VLDL / blood* Logistic Models Male Middle Aged Multivariate Analysis Predictive Value of Tests Probability Prognosis Prospective Studies Risk Assessment |
| Grant Support | |
ID/Acronym/Agency:
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U01 HL069757-08/HL/NHLBI NIH HHS; U01HL069757/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Lipoproteins, VLDL |
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