C-X-C Motif Chemokine Ligand 5 (CXCL5) Exhibits a U-Shaped Risk Profile for Mortality in Patients with Suspected Coronary Chest Pain

CXCL5 is a platelet-derived chemokine which promotes inflammatory responses in neutrophils and monocytes through CXCR2. Previous studies on CXCL5 in atherogenesis are to some degree conflicting, with scarce outcome data following acute coronary syndrome. This study aimed to assess the utility and risk profile of CXCL5 as a prognostic marker of all-cause mortality at 5-year follow-up in patients hospitalized for chest pain of suspected coronary origin. We measured CXCL5 levels in platelet-poor plasma in 826 consecutive patients included in the "Risk Markers in the Acute Coronary Syndrome" (RACS) study (ClinicalTrials.gov Identifier: NCT00521976). Stepwise Cox regression models, applying quintiles, were fitted for the biomarker with all-cause mortality within 5 years as the dependent variable. At 5-year 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 a 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% CI 1.06-2.39), <i>p</i> = 0.026, and Qt-5 vs. Qt-3: HR 1.44 (0.95-2.18), <i>p</i> = 0.082, respectively. Multivariable analysis: Qt-1 vs. Qt-3: HR 1.65 (1.09-2.48), <i>p</i> = 0.017, and Qt-5 vs. Qt-3: HR 1.52 (1.00-2.30), <i>p</i> = 0.049, respectively. The U-shaped relationship was statistically strengthened, employing a composite endpoint consisting of all-cause mortality, MI or stroke. 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.