The unadjusted association between YKL-40 and NSTE-ACS was attenuated after accounting for age and other baseline differences, and these findings do not establish an age-independent diagnostic role or support the routine diagnostic use of YKL-40 in NSTE-ACS.
Key Findings
Results
Serum YKL-40 concentrations were higher in NSTE-ACS patients than in non-ACS controls in unadjusted analysis.
Median YKL-40 was 832.1 ng/L in the NSTE-ACS group versus 552.6 ng/L in non-ACS controls (p = 0.002).
The study included 88 adults presenting to the emergency department with chest pain between December 2024 and March 2025.
60 patients had adjudicated NSTE-ACS (32 NSTEMI, 28 unstable angina) and 28 constituted the non-ACS control group.
Serum YKL-40 was measured at presentation using an enzyme-linked immunosorbent assay.
Results
Log-transformed YKL-40 showed moderate discriminatory performance for NSTE-ACS versus non-ACS controls in unadjusted analysis.
Area under the ROC curve was 0.709 (95% CI, 0.599–0.819; p < 0.001).
Unadjusted odds ratio per 1-standard-deviation increase in log-transformed YKL-40 was 1.89 (95% CI, 1.15–3.12; p = 0.013).
Assessment used receiver operating characteristic analysis, logistic regression, and bootstrap internal validation.
Results
The association between YKL-40 and NSTE-ACS was attenuated and became statistically non-significant after adjustment for age.
After adjustment for age, OR was 1.58 (95% CI, 0.92–2.71; p = 0.100).
Models additionally accounting for renal function and cardiovascular risk factors yielded consistent findings.
Analyses restricted to overlapping age ranges also yielded consistent findings.
Exploratory sensitivity analyses included Firth penalized regression.
Results
YKL-40 showed limited ability to discriminate between NSTEMI and unstable angina subtypes.
AUC for NSTEMI versus unstable angina discrimination was 0.527 (95% CI, 0.376–0.678).
The NSTE-ACS group comprised 32 patients with NSTEMI and 28 with unstable angina.
This subtype discrimination was a secondary outcome of the study.
Results
YKL-40 was not significantly associated with revascularization outcomes.
OR for revascularization was 1.76 (95% CI, 0.86–3.59; p = 0.120).
AUC for revascularization was 0.614.
Revascularization association was explored as a secondary outcome.
Results
YKL-40 was not significantly correlated with routinely measured inflammatory indices.
No significant correlation was found between YKL-40 and C-reactive protein, white blood cell count, or the neutrophil-to-lymphocyte ratio.
These correlations were explored as secondary outcomes.
This finding suggests YKL-40 does not track closely with standard inflammatory markers in this population.
What This Means
This research examined whether a protein called YKL-40, which is linked to vascular inflammation and tissue remodeling, could help doctors quickly identify patients in the emergency department who are having a type of heart attack or serious chest pain event known as non-ST-segment elevation acute coronary syndrome (NSTE-ACS). The study enrolled 88 adults presenting with chest pain, of whom 60 were diagnosed with NSTE-ACS and 28 were found to have non-cardiac causes of chest pain. Blood YKL-40 levels were measured at the time of arrival and compared between the two groups.
The study found that YKL-40 levels were notably higher in NSTE-ACS patients than in controls when analyzed without accounting for other factors. However, when the researchers adjusted for age differences between the groups, this association weakened substantially and was no longer statistically significant. YKL-40 also performed poorly at distinguishing between the two subtypes of NSTE-ACS (NSTEMI versus unstable angina), was not linked to whether patients needed a procedure to open blocked arteries, and did not correlate with common inflammation markers like C-reactive protein.
This research suggests that while YKL-40 levels are elevated in NSTE-ACS patients, this elevation appears to be partly explained by the fact that older patients are more likely to both have NSTE-ACS and have higher YKL-40 levels naturally. As a result, the findings do not support using YKL-40 as a standalone diagnostic tool in the emergency setting for this condition. Further larger studies would be needed to clarify whether YKL-40 offers any value beyond standard tests already available to clinicians.
Zabun E, Sayhan M, Çeliktürk E, Bozatlı S, Serttaş R, Seçgin Sayhan E. (2026). Serum YKL-40 in Non-ST-Segment Elevation Acute Coronary Syndrome: A Prospective Exploratory Emergency Department Study.. Medicina (Kaunas, Lithuania). https://doi.org/10.3390/medicina62081482