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Preliminary Communication
September 14, 2011

Association Between Serum Cathepsin S and Mortality in Older Adults

Author Affiliations

Author Affiliations: Department of Public Health and Caring Sciences, Sections of Geriatrics (Mss E. Jobs and Nerpin and Drs Ingelsson and Ärnlöv), Clinical Nutrition and Metabolism (Dr Risérus), and Oxidative Stress and Inflammation (Dr Basu), and Department of Medical Sciences (Drs Sundström, Larsson, and Lind), Uppsala University, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Dr Ingelsson); School of Health and Social Studies, Dalarna University, Falun, Sweden (Mss E. Jobs and Nerpin and Drs M. Jobs and Ärnlöv); and Laboratory of Biochemistry, Molecular Biology, and Nutrition, Faculty of Pharmacy, University of D’Auvergne, D’Auvergne, France (Dr Basu).

JAMA. 2011;306(10):1113-1121. doi:10.1001/jama.2011.1246
Abstract

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 follow-up: 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.

Results During 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.

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