(Circulation. 2000;101:1767.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Plasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men
From the Center for Cardiovascular Disease Prevention (P.M.R.) and the Divisions of Preventive Medicine (P.M.R., C.H.H.), Cardiovascular Diseases (P.M.R.), and the Channing Laboratory (M.J.S.), Brigham and Women’s Hospital; the Department of Ambulatory Care and Prevention (C.H.H.); and the Children’s Hospital Medical Center (N.R.), all at the Harvard Medical School, Boston, Mass.
Correspondence to Paul M. Ridker, MD, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115. E-mail pridker{at}partners.org
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.
Key Words: myocardial infarction • risk factors • inflammation • epidemiology • cytokines
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