C-X-C motif chemokine ligand 5 (CXCL5) is associated with risk of all-cause mortality in a U-shaped manner in patients admitted with chest pain of suspected coronary origin

Background CXCL5 is a platelet-derived chemokine which promotes inflammatory responses in neutrophils and monocytes through CXCR2 and to some degree also through CXCR1. Some studies have shown that CXCL5 can promote atherosclerotic plaque progression and impair myocardial tissue healing, but data on the prognostic impact of CXCL5 in acute coronary syndrome (ACS) are scarce and to some degree also conflicting. Thus, its potential as a prognostic biomarker in coronary atherothrombotic disease needs to be further explored. Aim To assess the utility and risk profile of CXCL5 as a prognostic marker of all-cause mortality at 5 years follow-up in patients hospitalized for chest pain of suspected coronary origin. Methods We measured CXCL5 levels in platelet-poor plasma by enzyme immunoassay in 826 of 871 consecutive patients. Stepwise Cox regression models, applying quintiles, were fitted for the biomarker with all-cause mortality within median 5 years as the dependent variable. The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model, adjusting for traditional clinical cardiovascular risk factors, with the addition of B-type natriuretic peptide, high sensitivity C-reactive protein, and troponin-T. Results At 5 years follow-up, 250 (30.3%) of the population had died; 34.5% in Quintile (Qt)-1, 32.1% in Qt-2, 23.5% in Qt-3, 29.1% in Qt-4, and 32.1% in Qt-5. Using Qt-3 as reference, both the univariate and multivariable analysis showed a U-shaped association between CXCL5 and all-cause mortality. Univariate analysis; Qt-1 vs. Qt-3: HR 1.59 (95% 1.06-2.39), p =0.026, and Qt-5 vs. Qt-3: HR 1.44 (0.95-2.18), p=0.082, respectively. Multivariable analysis; Qt-5 vs. Qt-3: HR 1.65 (1.09-2.48), p=0.017, and Qt-5 vs. Qt-3: HR 1.52 (1.00-2.30), p=0.049, respectively. Conclusion Our findings suggest that both too low and too high levels of CXCL5 may be harmful in patients admitted to hospital with chest pain of suspected coronary origin.