Inflammatory Markers and Risk of Heart Failure in Elderly Subjects Without Prior Myocardial Infarction

BACKGROUND: Experimental studies support a key role for cytokines in left ventricular remodeling. In congestive heart failure (CHF) patients, elevated plasma cytokine levels are associated with worse functional status and adverse prognosis. It is unclear whether cytokine levels can predict the incidence of CHF in asymptomatic individuals. METHODS AND RESULTS: We investigated the relations of serum interleukin-6 (IL-6), C-reactive protein (CRP), and spontaneous production of tumor necrosis factor-alpha (TNFalpha) by peripheral blood mononuclear cell (PBMC) to CHF incidence among 732 elderly Framingham Study subjects (mean age 78 years, 67% women) free of prior myocardial infarction and CHF. On follow-up (mean 5.2 years), 56 subjects (35 women) developed CHF. After adjustment for established risk factors, including the occurrence of myocardial infarction on follow-up, there was a 60 (PBMC TNFalpha) to 68% (serum IL-6) increase in risk of CHF per tertile increment in cytokine concentration (P=0.04, and 0.03, respectively, for trend). A serum CRP level > or =5 mg/dL was associated with a 2.8-fold increased risk of CHF (P=0.02). Subjects with elevated levels of all 3 biomarkers (serum IL-6 and PBMC TNFalpha >median values, CRP> or =5 mg/dL) had a markedly increased risk of CHF (hazards ratio 4.07 [95% CI 1.34 to 12.37], P=0.01) compared with the other subjects. CONCLUSIONS: In our elderly, community-based sample, a single determination of serum inflammatory markers, particularly elevated IL-6, was associated with increased risk of CHF in people without prior myocardial infarction. Additional epidemiological investigations are warranted to confirm the contribution of inflammation to the pathogenesis of CHF in the general population.