title: Association between serum cathepsin S and mortality in older adults.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors: Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden.
authors: Elisabeth
authors: E
authors: Jobs
authors: Erik
authors: E
authors: Ingelsson
authors: Ulf
authors: U
authors: Risérus
authors: Elisabet
authors: E
authors: Nerpin
authors: Magnus
authors: M
authors: Jobs
authors: Johan
authors: J
authors: Sundström
authors: Samar
authors: S
authors: Basu
authors: Anders
authors: A
authors: Larsson
authors: Lars
authors: L
authors: Lind
authors: Johan
authors: J
authors: Ärnlöv
mesh_terms: D000368:Aged; D002403:Cathepsins / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D009026:Mortality / Q000639:trends*; D013548:Sweden / Q000453:epidemiology
chemical_list: D002403:Cathepsins; C028217:cathepsin S