Association Between Serum Cathepsin S and Mortality in Older Adults

Study Questions:

Are elevated levels of cathepsin S associated with higher mortality risk?


Serum cathepsin S levels were measured in 1,996 subjects from two community-based cohorts. The mean age was 70-71 years, and the median follow-up was 8-12 years. The primary endpoint was mortality.


There were 513 deaths during the follow-up period. In multivariable Cox regression models, higher serum cathepsin S was associated with an increased risk for mortality, with a hazard ratio of 1.04 for each 1 unit increase in cathepsin S. In one of the cohorts, serum cathepsin S was also associated with cardiovascular mortality (131 deaths; hazard ratio [HR], for quintile 5 vs. quintiles 1-4, 1.62) and cancer mortality (148 deaths; HR for 1 unit increase of cathepsin S, 1.05).


The authors concluded that among elderly individuals in two independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk.


Cathepsin S is a cysteine protease shown in preclinical studies to promote development of atherosclerosis and cancer. Higher levels of cathepsin S in serum have been associated with inflammatory diseases in humans, although this study is the first prospective analysis of outcomes. Additional broad-based prospective trials as well as pharmacologic intervention trials will be needed to determine the clinical utility of cathepsin S measurements.

Keywords: Biological Markers, Cysteine Proteases, Cathepsins

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