C-reactive protein, interleukin-6 and tumor necrosis factor alpha as predictors of incident coronary and cardiovascular events and total mortality

Abstract

Previous studies have shown an association between serum C-reactive protein (CRP) and cardiovascular disease (CVD) risk. The roles of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha) are less well established. The aim of the present study was to analyze the associations of CRP, IL-6 and TNFalpha with incident coronary heart disease (CHD) events, CVD events, and total mortality. A random population sample, including men and women aged 25-64 years was examined in Finland in 1992. The sample size was 7,927 and 6,051 (76%) participated. The cohort was followed up until the end of 2001. During the follow-up, 151 incident CHD events, 205 CVD events and 183 deaths from any cause were observed. A stratified random subsample (n=313) was used as the comparison group. After adjustment for conventional CVD risk factors, CRP showed a significant association with CHD risk in men (HR=2.39, 1.08-5.28, comparing fourth quartile to the first quartile). This association remained significant after further adjustment for TNFalpha. TNFalpha also was a significant predictor of CHD among men, but the association was nonlinear (HR=2.21, 1.18-4.14 comparing the three upper quartiles to the first quartile). Further adjustment for CRP did not change this association substantially. Both CRP and TNFalpha predicted also all CVD events and total mortality among men. Among women the findings were nonsignificant. In conclusion, CRP and TNFalpha were significant, independent predictors of CHD and CVD events and total mortality among men. These findings provide further support to the important role of inflammation in the pathogenesis of CVD.

Relation of interleukin-6 level with coronary artery disease severity in patients undergoing coronary angiography

“…They reported that IL-6 was positively associated with an increased risk of all-cause and cardiovascular mortality (11). Contrary to that study, Tuomisto et al (12) reported that CRP and TNF-α, but not IL-6, were significant independent predictors of total mortality among men. Volpato et al reported that high IL-6 levels strongly affected the risk of mortality associated with the presence of CAD (13).…”

Optimization of the systemic inflammation‐based Glasgow Prognostic Score

“…19 The same high-sensitivity C-reactive protein threshold (> 3 mg/L) has also been used to predict survival in noncancer cohorts. 20,21 Taken together, the results would suggest that a C-reactive protein level of 3 mg/L is a potentially significant threshold in both cancer and noncancer cohorts. It raises the possibility that inflammationbased prognostic scores such as those examined herein will have prognostic value in noncancer cohorts.…”

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.…”