The prognostic value of interleukin 6 in multiple chronic diseases and all cause death: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aims: We aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population. Methods: We included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all cause death, atrial fibrillation, venous thromboembolism and cancer. Results: Median follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95% CI 1.23-10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017). Conclusions: IL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings.