Abstract 2321: CXCL5 Genotype is Associated with Mortality after Acute Coronary Syndromes
BACKGROUND: Epithelial neutrophil activating peptide (ENA-78) is a chemokine implicated in many inflammatory processes and may be involved in cardiovascular disease. We have previously found the −156 G>C variant in the ENA-78 gene (CXCL5) to be associated with elevated plasma ENA-78 concentrations and production from cultured leukocytes. Since leukocytes, including neutrophils, are involved in acute cardiovascular events, we hypothesized that the CXCL5 −156 G>C variant would be associated with worse event-free survival after acute coronary syndromes (ACS).
METHODS: A prospective cohort of ACS patients (n=704) with 3-year follow-up was assessed and CXCL5 was genotyped by Taqman. Cox proportional hazards models adjusting for age, race, sex, diabetes, heart failure, ACS type, coronary revascularization, and genotype were constructed in the entire cohort and separately by race. Kaplan Meier curves were estimated.
RESULTS: The −156C allele frequency was 0.17, 0.12, and 0.43 in the overall cohort, whites, and blacks, respectively. The −156C allele was associated with an increased risk mortality according to a recessive model of inheritance in the overall cohort (HR 2.8, 95% CI 1.4 –5.9) [Figure⇓], and in the white (HR 3.7, 95% CI 1.3–11.1) and black (HR 2.6, 95% CI 0.90 –7.3) subgroups.
CONCLUSIONS: CXCL5 −156 C/C genotype was associated with 2.8-fold higher mortality relative to other genotypes in ACS patients. The magnitude of risk was similar in both white and black patients. Taken with previous findings, CXCL5 genotype may represent a novel risk-stratification biomarker in ACS.