Background—Interleukin-6 (IL-6) plays a central role in inflammation and tissue injury. However, epidemiological data evaluating the role of IL-6 in atherogenesis are sparse.

Methods and Results—In a prospective study involving 14 916 apparently healthy men, we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infarction (MI) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up. Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not (1.81 versus 1.46 pg/mL; P=0.002). The risk of future MI increased with increasing quartiles of baseline IL-6 concentration (P for trend <0.001) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile (95% CI 1.3 to 4.3, P=0.005); for each quartile increase in IL-6, there was a 38% increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors, was stable over long periods of follow-up, and was present in all low-risk subgroups, including nonsmokers. Although the strongest correlate of IL-6 in these data was C-reactive protein (r=0.43, P<0.001), the relationship of IL-6 with subsequent risk remained after control for this factor (P<0.001).

Conclusions—In apparently healthy men, elevated levels of IL-6 are associated with increased risk of future MI. These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis.