BACKGROUND: Low grade inflammation is of pathogenic importance in the development of cardiovascular disease (CVD) and type 2 diabetes. The inflammation marker YKL-40 correlates with insulin resistance and is highly expressed in atherosclerotic plaques. We aimed to investigate whether YKL-40 could predict overall and cardiovascular (CV) mortality in a 50+ years population without known CVD. METHODS: A representative population sample of 639 individuals aged 50-89 years was recruited from general practices. Examination at baseline included echocardiography and blood and urine samples for CV risk factors and markers including lipids, high sensitive C-reactive protein (hsCRP), N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) and urinary albumin/creatinine-ratio (UACR). Median follow-up period was 5.0 (0.17-5.28) years. RESULTS: In subjects without diabetes and CVD at baseline, increasing YKL-40 levels independently predicted overall and CV mortality rate with hazard ratios of 1.58 (95% confidence interval (CI), 1.12-2.23, p=0.009) and 1.57 (95% CI, 1.00-2.46, p=0.049) after adjustment for age, sex, smoking, total cholesterol, hsCRP, NT-proBNP and UACR. In combined Kaplan-Meier analyses, baseline values of both YKL-40 and UACR above median significantly predicted increased cumulative overall and CV mortality rates in subjects without diabetes or CVD at baseline (30.6% vs.