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

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.