Chemokines and Incident Coronary Heart Disease

Abstract

Objectives— The chemokines monocyte chemoattractant protein-1 (MCP-1/CCL2), interleukin-8 (IL-8/CXCL8), and interferon-γ–inducible protein-10 (IP-10/CXCL10) have been reported to be involved in the development of atherosclerosis and type 2 diabetes. The aim of this study was to assess whether elevated systemic levels of these chemokines precede coronary events. Methods and Results— We investigated MCP-1, IL-8, and IP-10 serum levels in a case-cohort design based on data from 381 individuals (294 men, 87 women) with and 1977 individuals (1006 men, 971 women) without incident coronary heart disease (CHD) from the prospective, population-based MONICA/KORA Augsburg study (1984 to 2002). The mean follow-up time was 11.0 years. Baseline concentrations were significantly higher in cases compared with noncases ( P ≤0.001 for all chemokines). MCP-1 and IL-8 remained associated with CHD risk after adjustment for age, sex, and survey with hazard ratios (95% confidence intervals) comparing extreme tertiles of 1.39 (1.05 to 1.84) for MCP-1 and 1.48 (1.10 to 1.99) for IL-8. However, adjustment for further cardiovascular and immunologic risk factors attenuated the observed associations, and they became nonsignificant. Conclusions— Elevated systemic levels of the chemokines MCP-1, IL-8, and IP-10 precede CHD but do not represent independent risk factors. Thus, the associations are less pronounced than previously shown for type 2 diabetes. The study investigates whether elevated serum concentrations of the chemokines MCP-1, IL-8, and IP-10 precede coronary events in a prospective case-cohort design. Baseline concentrations of all 3 chemokines were significantly higher in cases compared with noncases, but the associations with CHD risk were no longer statistically significant in multivariable analysis.