High serum YKL‐40 level in a cohort of octogenarians is associated with increased risk of all‐cause mortality

Summary YKL‐40 is secreted by macrophages, neutrophils, chondrocytes, endothelial‐, vascular smooth muscle‐ and cancer cells. Interleukin (IL)‐6 stimulates YKL‐40 production in human in vivo studies. High serum YKL‐40 is associated with poor prognosis in patients with inflammatory diseases and cancer. We studied whether serum YKL‐40 was associated with systemic low‐level inflammation, an immune risk phenotype, and mortality in relatively healthy 80‐year old humans. Serum YKL‐40, IL‐6 and tumour necrosis factor (TNF)‐α were measured by enzyme‐linked immunosorbent assays (ELISAs) in octogenarians ( n  = 151) and serum YKL‐40 in 18–30‐year‐olds ( n  = 89). Fifty‐one of the octogenarians died during the 6‐year follow‐up. Serum YKL‐40 in octogenarians was higher compared to the level in young people (median 116 versus 31 μg/l, P  < 0·0005). Serum YKL‐40 correlated with serum IL‐6 in elderly women (Spearman's rho = 0·30, P  = 0·009) and men (rho = 0·25, P  = 0·003), but only with serum TNF‐α (rho = 0·23, P  = 0·05) and C‐reactive protein (CRP) (rho = 0·57, P  < 0·0005) among the elderly women. In addition, high serum level of YKL‐40 was associated with a low CD4 : CD8 cell ratio. Univariate analysis of serum YKL‐40 (logarithmically transformed and divided by tertiles) showed significant association with all‐cause mortality [tertile 3: hazard ratio (HR) = 2·38, 95% confidence interval (CI): 1·19–4·78, P  = 0·02]. The effect persisted after adjusting for potential confounders (sex, smoking, body mass index, chronic disease and anti‐inflammatory medicine). These results suggest that serum YKL‐40 is a prognostic and sensitive biomarker of all‐cause mortality in octogenarians.