Elevation in Circulating YKL-40 Levels in Patients with Stroke: A Review and Meta-Analysis

Abstract

Background: Stroke is the second most common cause of mortality and the third most common cause of disability. Modifiable risk factors for ischemic stroke include obesity, diabetes, hypertension, cigarette smoking, atrial fibrillation, dyslipidemia, carotid artery stenosis, sickle cell disease, postmenopausal hormone therapy, poor diet, and physical inactivity. There is data establishing the role of atherosclerosis in stroke. Evidence suggests a role for inflammation in the development of atherosclerosis and cerebrovascular disease. YKL-40, also called chitinase-3-like-1 (CHI3L1), is a novel inflammatory biomarker secreted by monocytes which has been elevated in stroke patients in multiple studies. Objective: The aim of this study was to assess if patients with elevated YKL-40 have increased odds of having a stroke. Methods: PubMed, Embase, CINAHL, Cochrane, Web of Science, and google scholar were searched using the keywords YKL-40, chitinase-3-like-1 (CHI3L1), human cartilage glycoprotein 39 (HC-gp39), stroke, ischemic stroke, cerebrovascular disease, atherosclerosis, and inflammation. English studies from 1960 to August 2017 addressing YKL-40 and stroke as well as YKL-40 levels in subjects with and without stroke were analyzed. YKL-40 levels were converted to ng/mL if provided in any other scale. Results: Ten studies met the inclusion criteria. Twelve datasets were analyzed, as 1 study included more than 1 dataset. Seven studies were case-control studies (n = 702 cases and n = 389 controls), while 3 studies were cross-sectional (n = 13,811). A random effects model was used. The standardized mean difference in YKL-40 levels between the stroke group and the control group was 2.21 (1.28-3.14, p < 0.001). Sensitivity analysis and cumulative analysis showed unchanged results. Funnel plots/precision plots indicated publication bias. Meta-regression analysis of case-control studies for the variables age and gender showed no significant impact of age (p = 0.33) and male gender (p = 0.11). Conclusion: High YKL-40 levels appear to be associated with stroke.