Association Between Serum Cathepsin S and Mortality in Older Adults

Context Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer.However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking.Objective To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.Design, Setting, and Participants Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n=1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of followup: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n=987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010).Serum samples were used to measure cathepsin S.Main Outcome Measure Total mortality. ResultsDuring follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk).In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06],P=.009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07],P=.04).In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37];P=.01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10];P=.01).Conclusions Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk.Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.