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

• Published in: Journal of proteome research Vol. 8; no. 6; pp. 2640 - 2649
• Main Authors: Heidema, A. Geert, Thissen, Uwe, Boer, Jolanda M. A, Bouwman, Freek G, Feskens, Edith J. M, Mariman, Edwin C. M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 05-06-2009
• Subjects: adhesion molecules; apolipoprotein-a-i; Biomarkers - blood; Blood Proteins - analysis; Body Mass Index; c-reactive protein; cardiovascular-disease; Cholesterol - blood; Coronary Disease - metabolism; Coronary Disease - mortality; coronary-heart-disease; growth-hormone; Humans; insulin-resistance; Least-Squares Analysis; Lipoproteins, HDL - blood; Male; metabolic syndrome; Middle Aged; Multivariate Analysis; normal-weight; Principal Component Analysis; Prognosis; risk-factors; Statistics, Nonparametric; proteomics; Partial Least Squares; CHD; HDL-cholesterol; BMI
• DOI: 10.1021/pr8006182
• EISSN: 1535-3907
• ISSN: 1535-3893

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.