Objective—The aim of this study was to assess the short- and long-term prognostic significance of interleukin-18 (IL-18) levels in patients with acute coronary syndromes (ACS). Methods and Results—In patients hospitalized with ACS (median age, 66 years; 30% females), we evaluated associations of serum IL-18 levels from day 1 (n=1261) with the short- (<3 months) and long-term (median, 7.6 years) risk of death, development of congestive heart failure (CHF), and myocardial infarction (MI). IL-18 was not significantly associated with short-term mortality. In the long term, IL-18 levels were significantly related to all-cause mortality, even after adjustment for clinical confounders (hazard ratio [HR], 1.19; 95% confidence interval, 1.07 to 1.33; P=0.002). Long-term, cardiovascular mortality was univariately related to IL-18, and the adjusted relation between noncardiovascular mortality and IL-18 was highly significant (HR, 1.36; 95% confidence interval, 1.11 to 1.67; P=0.003). IL-18 independently predicted CHF, MI, and cardiovascular death/CHF/MI in both the short and long term. Measurements from day 1 of ACS and 3 months after ACS had a similar power to predict late outcome. Conclusion—The addition of the measurement of IL-18 to clinical variables improved the prediction of risk of all-cause and noncardiovascular mortality. The association between IL-18 and noncardiovascular mortality is intriguing and warrants further study.
Objective-: CXCL16 and osteoprotegerin (OPG) both predict mortality in acute coronary syndromes. We hypothesized that a combination of CXCL16 and OPG concentrations would add prognostic information to the Global Registry of Acute Coronary Events (GRACE) score in patients hospitalized for acute coronary syndromes. Methods and Results-: We assessed the associations between circulating OPG and soluble CXCL16 levels, obtained within 24 hours of admission (day 1) and after 3 months, and mortality, heart failure and reinfarction in 1322 patients admitted with acute coronary syndromes. After adjustment for the GRACE score, medication, diabetes mellitus and sex, the combination of high values (fourth quartile) for OPG and CXCL16 at baseline was associated with increased short-term (3 months) cardiovascular mortality (hazard ratio, 3.28; 95% CI, 1.84-5.82; P<0.0001). The combined high values were also significantly associated with the long-term (median 91 months) prognosis after adjustment, with hazard ratios 2.18 for cardiovascular mortality (95% CI, 1.62-2.92; P<0.0001), and 2.22 for heart failure (95% CI, 1.67-2.96; P<0.0001). These long-term associations remained significant after further adjustment for left ventricular ejection fraction, C-reactive protein, and pro B-type natriuretic peptide. For 635 patients with blood samples within 24 hours and at 3 months, the combination of high CXCL16 and OPG values (fourth quartile) in the early or stable phase was of a similar order associated with mortality and morbidity beyond 3 months. Conclusion-: Circulating CXCL16 and OPG are independent predictors of long-term mortality and heart failure development in acute coronary syndromes patients, even after extensive adjustments. Their combination gives more information than either marker alone.