Increased plasma YKL-40 is associated with short-term survival in patients with cardiovascular disease and cancer. We tested the hypothesis that increased plasma YKL-40 is associated with total and disease-specific mortality in the general population.

We measured plasma YKL-40 in 8899 study participants, aged 20–95 years, in the Copenhagen City Heart Study from the Danish general population who were followed for 16 years: 3059 died, 2158 had ischemic cardiovascular disease, 2271 had cancer, and 2820 had other diseases associated with increased YKL-40. Hazard ratios for early death and absolute 10-year mortality rates were calculated according to plasma YKL-40 percentile groupings computed within sex and age decade: 0%–33%, 34%–66%, 67%–90%, 91%–95%, and 96%–100%.

Median survival age decreased from 83 years for participants with plasma YKL-40 in category 0%–33% to 69 years in category 96%–100% (trend, P < 0.0001). Risk of early death was increased (multifactorially adjusted hazard ratios) by 10% for YKL-40 category 34%–66%, by 30% for 67%–90%, by 70% for 91%–95%, and by 90% for 96%–100% vs YKL-40 category 0%–33% (trend, P < 0.0001). Corresponding increases in participants with ischemic cardiovascular disease were 10%, 20%, 80%, and 60% (P < 0.0001); in those with cancer were 10%, 20%, 50%, and 70% (P < 0.0001); and in those with other diseases were 10%, 20%, 40%, and 60% (P < 0.0001). Highest absolute 10-year mortality rates were 78% and 90% in women and men, respectively, who were >70 years old, smoked, and were in YKL-40 category 96%–100%.

Increased plasma YKL-40 is associated with risk of early death from cardiovascular disease, cancer, and other diseases in the general population.