Serum YKL-40 levels correlate with infarct volume, stroke severity, and functional outcome in acute ischemic stroke patients

Abstract

Background and purpose: YKL-40 is associated with various neurological disorders. However, circulatory YKL-40 levels early after onset of acute ischemic stroke (AIS) have not been systematically assessed. We aimed to identify the temporal changes and clinical usefulness of measuring serum YKL-40 immediately following AIS.

Methods: Serum YKL-40 and C-reactive protein (CRP) levels were monitored over time in AIS patients (n = 105) and compared with those of stroke-free controls (n = 34). Infarct volume and stroke severity (National Institutes of Health Stroke Scale; NIHSS) were measured within 48 hours of symptom onset, and functional outcome (modified Rankin Scale; mRS) was measured 3 months after AIS.

Results: Within 12 hours of symptom onset, levels of YKL-40 (251 vs. 41 ng/mL) and CRP (1.50 vs. 0.96 µg/mL) were elevated in AIS patients compared to controls. The power of YKL-40 for discriminating AIS patients from controls was superior to that of CRP (area under the curve 0.84 vs. 0.64) and YKL-40 (r = 0.26, P<0.001) but not CRP levels were correlated with mRS. On day 2 of admission (D2), YKL-40 levels correlated with infarct volume and NIHSS. High YKL-40 levels predicted poor functional outcome (odds ratio 5.73, P = 0.03). YKL-40 levels peaked on D2 and declined on D3, whereas CRP levels were highest on D3.

Conclusions: Our results demonstrate serial changes in serum YKL-40 levels immediately following AIS and provide the first evidence that it is a valid indicator of AIS extent and an early predictor of functional outcome.

Figure 1. Levels of serum YKL-40 (A) and CRP (B) in acute ischemic stroke patients and controls.

Each box indicates the median. Horizontal lines indicate the interquartile ranges. (C) Diagnostic accuracies of serum YKL-40 and CRP for discriminating acute ischemic stroke patients (n = 100; for statistical assessment of the differences between D1 and D2, 5 of 105 patients were excluded because they [n = 5] dropped out of the D2 test) from controls (n = 34) using receiver operating characteristic (ROC) curves. Numbers in square brackets indicate diagnostic accuracies (area under the ROC curves). D1, within 12 hours of symptom onset; D2, 18–24 hours from baseline (D1); CRP, C-reactive protein. *P<0.05. ^a P<0.05, vs. YKL-40 on D2. ^b P<0.05, vs. CRP on D1. ^c P<0.05, vs. CRP on D2. ^d P<0.05, vs. YKL-40 on D1.

Figure 2. Levels of serum YKL-40 (A) and CRP (B) depend on stroke subtype (in noncardiogenic stroke).

Each box indicates the median. Horizontal lines indicate the interquartile ranges. D1, within 12 hours of symptom onset; D2, 18–24 hours from baseline (D1); CRP, C-reactive protein; SVO, small-vessel occlusion or lacunar; LAA, large artery atherosclerosis or atherothrombosis. *P<0.05.

Figure 3. Temporal changes in YKL-40 (A) and CRP (B) levels following acute ischemic stroke.

Open markers indicate serially analyzed protein levels in each patient. Each box indicates the median, and the closed markers indicate the interquartile ranges. D1, within 12 hours of symptom onset; D2, 18–24 hours from baseline (D1); D3, 36–48 hours from baseline; CRP, C-reactive protein. *P<0.05.