Oxidative damage in the gastrocnemius predicts long-term survival in patients with peripheral artery disease

IF 5.4 Q1 GERIATRICS & GERONTOLOGY
Panagiotis Koutakis, Hernan Hernandez, Dimitrios Miserlis, Jonathan R. Thompson, Evlampia Papoutsi, Constance J. Mietus, Gleb Haynatzki, Julian K. Kim, George P. Casale, Iraklis I. Pipinos
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Abstract

Patients with peripheral artery disease (PAD) have increased mortality rates and a myopathy in their affected legs which is characterized by increased oxidative damage, reduced antioxidant enzymatic activity and defective mitochondrial bioenergetics. This study evaluated the hypothesis that increased levels of oxidative damage in gastrocnemius biopsies from patients with PAD predict long-term mortality rates. Oxidative damage was quantified as carbonyl adducts in myofibers of the gastrocnemius of PAD patients. The oxidative stress data were grouped into tertiles and the 5-year, all-cause mortality for each tertile was determined by Kaplan-Meier curves and compared by the Modified Peto test. A Cox-regression model was used to control the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Of the 240 study participants, 99 died during a mean follow up of 37.8 months. Patients in the highest tertile of oxidative damage demonstrated the highest 5-year mortality rate. The mortality hazard ratios (HR) from the Cox analysis were statistically significant for oxidative damage (lowest vs middle tertile; HR = 6.33; p = 0.0001 and lowest vs highest; HR = 8.37; p < 0.0001). Survival analysis of a contemporaneous population of PAD patients identifies abundance of carbonyl adducts in myofibers of their gastrocnemius as a predictor of mortality rate independently of ankle-brachial index, disease stage and other clinical and myopathy-related covariates.

腓肠肌的氧化损伤可预测外周动脉疾病患者的长期存活率
外周动脉疾病(PAD)患者的死亡率升高,患腿肌病的特点是氧化损伤增加、抗氧化酶活性降低和线粒体生物能缺陷。本研究评估了一个假设,即 PAD 患者腓肠肌活检组织中氧化损伤水平的增加可预测长期死亡率。氧化损伤被量化为 PAD 患者腓肠肌肌纤维中的羰基加合物。氧化应激数据被分为三等分,每个三等分的5年全因死亡率通过Kaplan-Meier曲线确定,并通过修正的Peto检验进行比较。采用 Cox 回归模型控制临床特征的影响。结果根据年龄、性别、种族、体重指数、踝肱指数、吸烟、体力活动和合并症进行了调整。在 240 名研究参与者中,有 99 人在平均 37.8 个月的随访期间死亡。氧化损伤程度最高的患者的 5 年死亡率最高。Cox分析得出的死亡率危险比(HR)对氧化损伤有显著的统计学意义(最低与中间三分位数;HR = 6.33;p = 0.0001;最低与最高;HR = 8.37;p < 0.0001)。对同期PAD患者进行的生存分析表明,腓肠肌肌纤维中羰基加合物的丰度是预测死亡率的一个因素,与踝肱指数、疾病分期及其他临床和肌病相关协变量无关。
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来源期刊
NPJ Aging and Mechanisms of Disease
NPJ Aging and Mechanisms of Disease Medicine-Geriatrics and Gerontology
自引率
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0
审稿时长
8 weeks
期刊介绍: npj Aging and Mechanisms of Disease is an online open access journal that provides a forum for the world’s most important research in the fields of aging and aging-related disease. The journal publishes papers from all relevant disciplines, encouraging those that shed light on the mechanisms behind aging and the associated diseases. The journal’s scope includes, but is not restricted to, the following areas (not listed in order of preference): • cellular and molecular mechanisms of aging and aging-related diseases • interventions to affect the process of aging and longevity • homeostatic regulation and aging • age-associated complications • translational research into prevention and treatment of aging-related diseases • mechanistic bases for epidemiological aspects of aging-related disease.
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