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

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.

HDL in humans with cardiovascular disease exhibits a proteomic signature

“…The regression vector indicates channels on the m/z axis of a mass spectrum that differentiate the two sample classes (Fig. 2C) [32]. The channels in the regression vector with positive values can be used to identify peptides (and indirectly proteins) that are more abundant in CAD samples than in control samples, while the channels with negative values in the regression vector can be used to identify peptides that are less abundant in the CAD samples.…”

Mass spectrometry of peptides and proteins from human blood

“…A novel affinity purification of human ceruloplasmin was achieved with an acharan sulfate stationary phase . Where reagents are available, affinity chromatography has been shown to be at least as sensitive as multiple partition chromatography methods at or below the ng/mL range (Heidema et al, 2009). However, given the limited number and cost of affinity reagents (Tegel et al, 2009), there remains a need to fractionate and discover blood proteins by standard separation techniques.…”

“…Specific proteins, enzyme activities, or modifications of the structure of blood proteins may serve as biomarkers of disease, environmental factors, therapeutic efficacy or host response (Teodoro et al, 2006;Taguchi et al, 2007;de Roos et al, 2008;Matsumoto et al, 2009). Presently, the majority of proteins in the blood are measured by ELISA assays (Heidema et al, 2009) or by enzyme activity but mass spectrometry has the potential to replace these assays in some cases. The ionization (Karas & Hillenkamp, 1988;Fenn et al, 1989;Nakanishi et al, 1994) and mass spectrometric analysis of blood polypeptides (Davis et al, 1995;Haynes et al, 1998) are able to detect many of the proteins known to be contained in the blood (Putnam, 1975;Tietz, 2001).…”

Dietary patterns, subclinical inflammation, incident coronary heart disease and mortality in middle-aged men from the MONICA/KORA Augsburg cohort study

“…Increased levels of the acute phase protein C-reactive protein (CRP), and the proinflammatory cytokines interleukin (IL)-6 and IL-18 were found to be associated with the risk of coronary heart disease (CHD; Blankenberg et al, 2003;Koenig et al, 2006;Kaptoge et al, 2010;Rodondi et al, 2010), death from CHD (Heidema et al, 2009) and all-cause mortality (Stork et al, 2006;Tuomisto et al, 2006;Jylha et al, 2007). In addition, single food components have been found to be related to inflammatory markers; higher intakes of dietary fibre (Ma et al, 2008;Herder et al, 2009;Wannamethee et al, 2009), whole-grain products (Qi et al, 2006;Lutsey et al, 2007), fruit and vegetables (Wannamethee et al, 2006;Holt et al, 2009), nuts (Salas-Salvado et al, 2008;Casas-Agustench et al, 2010), and a moderate alcohol intake (Wang et al, 2008;Oliveira et al, 2010) were associated with lower concentrations of several immune mediators in the circulation.…”