Abstract 16339: Independent Relevance of Cytokines for Risk of Coronary Heart Disease

Abstract

Aims: Genetic studies have refuted a causal role for C-reactive protein (CRP) in the etiology of coronary heart disease (CHD), but prompted increased interest in susceptibility variants affecting the IL-5 and IL-6 pathways and their impact on CHD risk. This study compared the independent relevance of plasma levels of several cytokines for prediction of CHD.

Methods: The PROCARDIS case-control study compared the associations of five cytokines with CHD risk in 980 CHD cases and 985 controls. Plasma levels of cytokines (IL-6, IFN-γ, IL-5, IL-1β and TNF-α) were measured using a Meso Scale Discovery assay platform. Spearman correlation coefficients were used to examine associations with CRP in controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for CHD risk for extreme thirds of cytokines after adjustment for age, sex and country, and additionally for established risk factors (smoking, diabetes mellitus, hypertension, blood lipids and cystatin C).

Results: Among controls, plasma levels of IL-6 were strongly correlated with CRP (r = 0.46), whereas the correlations of other cytokines with CRP were much weaker. The CHD ORs for extreme thirds of IL-6 were substantially attenuated, but remained statistically significant after adjustment for established risk factors (5.15 [95%CI: 3.94-6.73] vs 2.32 [1.69-3.18]). In contrast, the other cytokines were more modestly associated with CHD after adjustment for established risk factors (figure).

Conclusions: IL-6 was most strongly associated with CHD, indicating a greater relevance for CHD risk prediction and as a potential therapeutic target for CHD prevention compared with the other cytokines studied.