Serum YKL-40 in Non-ST-Segment Elevation Acute Coronary Syndrome: A Prospective Exploratory Emergency Department...

Background and Objectives: Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) is a heterogeneous emergency condition in which early diagnostic assessment may be challenging. YKL-40 is associated with vascular inflammation and extracellular matrix remodeling, but its age-independent diagnostic relevance in NSTE-ACS remains uncertain. We evaluated the association and discriminatory performance of serum YKL-40 in patients with adjudicated NSTE-ACS versus non-ACS chest-pain controls; subtype discrimination, revascularization, and correlations with routinely measured inflammatory indices were explored as secondary outcomes. Materials and Methods: This prospective, single-center observational study included 88 adults presenting to the emergency department with chest pain between December 2024 and March 2025. Sixty had adjudicated NSTE-ACS, including 32 with non-ST-segment elevation myocardial infarction and 28 with unstable angina, while 28 constituted the non-ACS control group. Serum YKL-40 was measured at presentation using an enzyme-linked immunosorbent assay. Patient-control discrimination was assessed using receiver operating characteristic analysis, logistic regression, and bootstrap internal validation. Exploratory sensitivity analyses included Firth penalized regression and comparisons restricted to overlapping age ranges. Results: In the unadjusted analysis, serum YKL-40 concentrations were higher in the NSTE-ACS group than in non-ACS controls (median, 832.1 vs. 552.6 ng/L; p = 0.002). Log-transformed YKL-40 yielded an area under the curve of 0.709 (95% CI, 0.599-0.819; p < 0.001) and was associated with NSTE-ACS status (OR per 1-standard-deviation increase, 1.89; 95% CI, 1.15-3.12; p = 0.013). After adjustment for age, the association was attenuated and no longer statistically significant (OR, 1.58; 95% CI, 0.92-2.71; p = 0.100). Models additionally accounting for renal function and cardiovascular risk factors, together with analyses restricted to overlapping age ranges, yielded consistent findings. YKL-40 showed limited discrimination between NSTEMI and unstable angina (AUC, 0.527; 95% CI, 0.376-0.678), was not significantly associated with revascularization (OR, 1.76; 95% CI, 0.86-3.59; p = 0.120; AUC, 0.614), and was not significantly correlated with C-reactive protein, white blood cell count, or the neutrophil-to-lymphocyte ratio. Conclusions: The unadjusted association between YKL-40 and NSTE-ACS was attenuated after accounting for age and other baseline differences. These findings do not establish an age-independent diagnostic role or support the routine diagnostic use of YKL-40 in NSTE-ACS.