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Elevated cathepsin S serum levels linked with increased risk for death

Jobs E. JAMA. 2011;doi:10.1001/jama.2011.1246.

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Higher serum cathepsin S levels are associated with an increased mortality risk among elderly patients, according to a study.

In a prospective study using two community-based cohorts — the Uppsala Longitudinal Study of Adult Men (ULSAM) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) — serum samples were used to measure cathepsin S. Both studies took place in Uppsala, Sweden. ULSAM was initiated in 1970 and had 1,009 participants. PIVUS took place between 2001 and 2004 and had 987 participants.

Anthropometrical measurements, BP, blood sampling and questionnaires regarding socioeconomic status, medical history, smoking habits, medication use and physical activity level were investigated by researchers in both studies. Serum levels of cathepsin S, inflammatory markers and cystatin C were all measured by an enzyme-linked immunosorbent assay. Both studies used Cox proportional hazard regression and three multivariable models to find associations of serum level of cathepsin S with total mortality. The ULSAM study included CV and cancer mortality.

When adjusted for age, systolic BP, diabetes, smoking status, BMI, total cholesterol, HDL, antihypertensive treatment, lipid-lowering treatment and history of CVD, Cox regression models showed that higher serum cathepsin S was associated with an increased risk for mortality. Cathepsin S was also associated with an increased mortality risk for CV and cancer mortality in the ULSAM cohort. In a follow-up, 413 participants in the ULSAM cohort died of CVD (131 deaths) and cancer (148 deaths), whereas 100 participants in the PIVUS cohort died. Incidence rate per 1 unit increase of cathepsin S was 0.44/100 person-years at risk in ULSAM, and 0.15/100 person-years at risk in PIVUS. Total mortality after adjustment for age, sex, lifestyle factors and established CV risk factors had an HR of 1.04 in ULSAM and 1.03 for PIVUS. In ULSAM, CV mortality had an HR of 1.05 and cancer mortality had an HR of 1.06.

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