Departments of *Surgery and †Biostatistics, University of Nebraska Medical Center, Omaha, NE ‡Department of Surgery and VA Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE.
Ann Surg. 2015 Mar;261(3):605-10. doi: 10.1097/SLA.0000000000000643.
This study evaluated the hypothesis that protein concentration and mitochondrial content in gastrocnemius biopsies from patients with peripheral arterial disease (PAD) predict mortality rates.
PAD patients experience advancing myopathy characterized by mitochondrial dysfunction, myofiber degradation, and fibrosis in their ischemic legs, along with increased mortality rates.
Samples from the gastrocnemius of PAD patients were used for all analyses. Protein concentration was normalized to muscle wet weight, and citrate synthase activity (standard measure of mitochondrial content in cells) was normalized to muscle wet weight and protein concentration. Protein and citrate synthase data were grouped into tertiles and 5-year, all-cause mortality for each tertile was determined with Kaplan-Meier curves and compared by the modified Peto-Peto test. A Cox-regression model for each variable controlled for the effects of clinical characteristics.
Of the 187 study participants, 46 died during a mean follow-up of 23.0 months. Five-year mortality rate was highest for patients in the lowest tertile of protein concentration. Mortality was lowest for patients in the middle tertile of citrate synthase activity when normalized to either muscle wet weight or protein concentration. The mortality hazard ratios (HRs) from the Cox analysis were statistically significant for protein concentration normalized to muscle wet weight (lowest vs middle tertile; HR = 2.93; P = 0.008) and citrate synthase normalized to protein concentration (lowest vs middle tertile; HR = 4.68; P = 0.003; and lowest vs highest tertile; HR = 2.36; P = 0.027).
Survival analysis of a contemporaneous population of PAD patients identifies protein and mitochondrial content of their gastrocnemius as predictors of mortality rate.
本研究评估了这样一个假设，即来自外周动脉疾病（PAD）患者的比目鱼肌活检中的蛋白质浓度和线粒体含量可预测死亡率。
PAD 患者会出现进行性肌病，其特征为缺血腿部的线粒体功能障碍、肌纤维降解和纤维化，以及死亡率增加。
所有分析均使用 PAD 患者的比目鱼肌样本。蛋白质浓度按肌肉湿重标准化，柠檬酸合酶活性（细胞中线粒体含量的标准衡量标准）按肌肉湿重和蛋白质浓度标准化。将蛋白质和柠檬酸合酶数据分为三分位数，并通过 Kaplan-Meier 曲线确定每个三分位数的 5 年全因死亡率，并通过修正的 Peto-Peto 检验进行比较。每个变量的 Cox 回归模型均控制了临床特征的影响。
在 187 名研究参与者中，有 46 人在平均 23.0 个月的随访期间死亡。蛋白质浓度最低三分位的患者 5 年死亡率最高。当按肌肉湿重或蛋白质浓度标准化时，柠檬酸合酶活性的中间三分位患者的死亡率最低。Cox 分析的死亡率风险比（HR）在统计学上具有显著意义，即按肌肉湿重标准化的蛋白质浓度（最低与中间三分位；HR=2.93；P=0.008）和按蛋白质浓度标准化的柠檬酸合酶（最低与中间三分位；HR=4.68；P=0.003；和最低与最高三分位；HR=2.36；P=0.027）。
对当代 PAD 患者人群的生存分析确定了其比目鱼肌的蛋白质和线粒体含量可预测死亡率。
