Elevated levels of cathepsin S, a protein biomarker, in elderly patients increased the risk of death and was linked to the development of cardiovascular disease and cancer, according to data presented Aug. 30 at the European Society of Cardiology Congress in Paris and simultaneously published in the Journal of the American Medical Association.
“Current data regarding factors that influence circulating levels of cathepsin S are scarce,” Elisabeth Jobs, MSc, of Uppsala University in Uppsala, Sweden, and colleagues wrote. “Previous studies have reported higher circulating levels of cathepsin S in patients with obesity, diabetes or cardiovascular disease.”
To better understand the possible association between cathepsin S levels and mortality, Jobs and colleagues performed a prospective study using two community-based cohorts: the Uppsala Longitudinal Study of Adult Men (1,009 patients) and the Prospective Investigation of the Vasculature in Uppsala Seniors (987 patients). The researchers used serum samples to measure cathepsin S, a cysteine protease.
The Uppsala Longitudinal Study of Adult Men (ULSAM) cohort included 50-year-old men born between 1920 and 1924 who lived in Uppsala, Sweden. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort included 70-year-olds living in Uppsala between 2001 and 2004; 50 percent were women.
The researchers reported 413 deaths in the ULSAM cohort and 100 deaths in the PIVUS cohort. When the researchers adjusted for age, blood pressure, diabetes, smoking status, body mass index, total cholesterol, HDL cholesterol, antihypertensive treatment, lipid-lowering medications and history of CV disease, a higher serum cathepsin S was found to be associated with an increased risk of mortality.
In the ULSAM cohort, cathepsin S was also linked to a higher rate of CV mortality and cancer mortality, 131 deaths and 148 deaths, respectively. Jobs et al reported the association between cathepsin S and mortality to be stronger in women in the PIVUS cohort.
The researchers said that the cathepsin S biomarker can aggravate foam cell formation by “degrading low-density lipoprotein cholesterol and reducing cholesterol efflux from macrophages.” The fact that the association between cathepsin S and CV mortality was stronger in patients who had a documented history of CV disease could indicate that cathepsin S levels could be a marker of plaque vulnerability.
The authors wrote that it would be feasible to assess serum levels of cathepsin S in the population, but future interventional trials will be necessary to evaluate whether cathepsin S inhibition is a safe and effective target for CV disease.
“If these drugs are found to be effective, tools for identifying target groups and for monitoring treatment need to be developed,” the authors wrote.