Soluble CXCL16 Predicts Long-Term Mortality in Acute Coronary Syndromes

Abstract

Background— CXCL16/SR-PSOX is an interferon-γ–regulated chemokine and scavenger receptor for oxidized low-density lipoprotein that is expressed in atherosclerotic lesions. Proteolytic cleavage of membrane-bound CXCL16 releases soluble CXCL16, which may promote migration of effector T cells and augment a proatherogenic inflammatory response. We hypothesized that soluble CXCL16 concentrations are associated with long-term outcome in patients with acute coronary syndromes. Methods and Results— We assessed the association between circulating CXCL16 levels obtained within 24 hours after admission and time to death in 1351 patients (median age 67 years, 30% female) with a diagnosis of unstable angina, non–ST-segment–elevation myocardial infarction, or ST-segment–elevation myocardial infarction. During a median follow-up time of 81 months, 377 patients died. Increased levels of CXCL16 were prognostically unfavorable; the fourth versus first quartile was associated with higher risk of death (hazard ratio 2.1; 95% CI 1.6 to 2.8; P <0.0001), triple risk of developing heart failure (hazard ratio 3.0; 95% CI 1.8 to 5.1; P <0.0001), and a doubling of the risk of rehospitalization for myocardial infarction (hazard ratio 2.1; 95% CI 1.3 to 3.3; P =0.002). After adjustment for conventional risk markers, logarithmically transformed CXCL16 level remained a strong independent indicator of long-term mortality (hazard ratio 1.21; 95% CI 1.09 to 1.36 per 1 SD increase in CXCL16; P =0.0006) and congestive heart failure development (hazard ratio 1.25; 95% CI 1.05 to 1.48; P =0.01). In a subsample of 714 patients, after further adjustment for troponin T, high-sensitive C-reactive protein, pro–B-type natriuretic peptide, and left ventricular ejection fraction, CXCL16 still provided significant additional prognostic information on mortality (hazard ratio 1.21; 95% CI 1.02 to 1.42 per 1 SD increase in CXCL16; P =0.02). Conclusions— In patients with an acute coronary syndrome, CXCL16 levels obtained within 24 hours of admission are associated with long-term mortality after adjustment for other risk factors.