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The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: Applying multivariate statistics to identify proteins with prognostic value and biological relevance

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Author: Geert Heidema, A. · Thissen, U. · Boer, J.M.A. · Bouwman, F.G. · Feskens, E.J.M. · Mariman, E.C.M.
Type:article
Date:2009
Institution: TNO Kwaliteit van Leven
Source:Journal of Proteome Research, 6, 8, 2640-2649
Identifier: 241591
doi: doi:10.1021/pr8006182
Keywords: Biology Health Nutrition · Analytical research · BMI · CHD · HDL-cholesterol · Partial least squares · Proteomics · alpha 2 macroglobulin · apolipoprotein A1 · beta 2 microglobulin · C reactive protein · CD40 antigen · cholesterol · fibrinogen · growth hormone · high density lipoprotein cholesterol · immunoglobulin M · insulin · leptin · macrophage derived chemokine · macrophage inflammatory protein 1beta · matrix metalloproteinase · plasma protein · plasminogen activator inhibitor 1 · pregnancy associated plasma protein A · tissue inhibitor of metalloproteinase 1 · vascular cell adhesion molecule 1 · vasculotropin · adult · angiogenesis · article · blood clotting · body mass · cardiovascular disease · case control study · cholesterol blood level · cholesterol metabolism · clinical article · controlled study · disease association · enzyme activity · follow up · human · immune response · immunoassay · inflammation · ischemic heart disease · lipid metabolism · male · mortality · multivariate analysis · Netherlands · partial least squares regression · principal component analysis · priority journal · prognosis · protein analysis · proteomics · risk factor · statistical analysis · univariate analysis

Abstract

In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch monitoring project for cardiovascular disease risk factors, men who died of CHD between initial participation (1987-1991) and end of follow-up (January 1, 2000) (N = 44) and matched controls (N = 44) were selected. Baseline plasma concentrations of proteins were measured by a multiplex immunoassay. With the use of PLS, we identified 15 proteins with prognostic value for CHD mortality and sets of proteins associated with the intermediate end points. Subsequently, sets of proteins and intermediate end points were analyzed together by Principal Components Analysis, indicating that proteins involved in inflammation explained most of the variance, followed by proteins involved in metabolism and proteins associated with total-C. This study is one of the first in which the association of a large number of plasma proteins with CHD mortality and intermediate end points is investigated by applying multivariate statistics, providing insight in the relationships among proteins, intermediate end points and CHD mortality, and a set of proteins with prognostic value. © 2009 American Chemical Society.