Department of Public Health and Caring Sciences, Section of Geriatrics, Uppsala University, Uppsala, Sweden.
JAMA. 2011 Sep 14;306(10):1113-21. doi: 10.1001/jama.2011.1246. Epub 2011 Aug 29.
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.
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.
Total mortality.
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).
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.
实验数据表明，组织蛋白酶 S 是一种半胱氨酸蛋白酶，它参与了导致心血管疾病和癌症的复杂途径。然而，关于循环组织蛋白酶 S 水平与死亡率之间潜在关联的前瞻性数据仍然缺乏。
在两个独立的老年男女队列中，研究循环组织蛋白酶 S 水平与死亡率之间的关联。
设计、地点和参与者：这是一项前瞻性研究，使用了两个基于社区的队列，乌普萨拉成年男性纵向研究（ULSAM；n = 1009；平均年龄：71 岁；基线期：1991-1995 年；中位随访期：12.6 年；随访结束：2006 年）和乌普萨拉老年人血管前瞻性研究（PIVUS；n = 987；50%为女性；平均年龄：70 岁；基线期：2001-2004 年；中位随访期：7.9 年；随访结束：2010 年）。血清样本用于测量组织蛋白酶 S。
总死亡率。
在随访期间，ULSAM 队列中有 413 名参与者死亡（发生率：每 100 人-年风险 3.59 人），PIVUS 队列中有 100 名参与者死亡（发生率：每 100 人-年风险 1.32 人）。在多变量 Cox 回归模型中，调整年龄、收缩压、糖尿病、吸烟状况、体重指数、总胆固醇、高密度脂蛋白胆固醇、降压治疗、降脂治疗和心血管疾病史后，较高的血清组织蛋白酶 S 与死亡率增加相关（ULSAM 队列：组织蛋白酶 S 增加 1 单位的风险比[HR]，1.04[95%CI，1.01-1.06]，P =.009；PIVUS 队列：组织蛋白酶 S 增加 1 单位的 HR，1.03[95%CI，1.00-1.07]，P =.04）。在 ULSAM 队列中，血清组织蛋白酶 S 也与心血管死亡率（131 例死亡；第 5 五分位组与第 1-4 五分位组的 HR，1.62[95%CI，1.11-2.37]；P =.01）和癌症死亡率（148 例死亡；组织蛋白酶 S 增加 1 单位的 HR，1.05[95%CI，1.01-1.10]；P =.01）相关。
在两个独立的老年人群队列中，较高的血清组织蛋白酶 S 水平与死亡率升高相关。需要进一步研究以阐明组织蛋白酶 S 的作用，以及其测量是否具有临床应用价值。
