Abstract 19119: Oxidative Damage in the Gastrocnemius Predicts Mortality Rates in Patients With Peripheral Artery Disease
Introduction: Patients with peripheral artery disease (PAD) experience advancing myopathy in their ischemic legs along with increased functional impairment and increased mortality rates. Myofiber oxidative damage is a central mechanism in the development of PAD myopathy and correlates with degree of functional impairment and decline.
Hypothesis: This study evaluated the hypothesis that myofiber oxidative damage in gastrocnemius biopsies from patients with PAD predicts mortality rates.
Methods: Oxidative damage was quantified as levels of protein carbonyl groups in the myofibers of gastrocnemius samples obtained from PAD patients. Carbonyl 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 for the effects of clinical characteristics. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities.
Results: 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 five-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).
Conclusions: Survival analysis of a contemporaneous population of PAD patients identifies protein carbonyl groups of their gastrocnemius as a predictor of mortality rate independently of ABI and other covariates. This supports a role of oxidative stress and ischemic myopathy as a contributor to mortality in PAD. Further evaluation of the possible benefits of antioxidant therapy in PAD is warranted.
Author Disclosures: P. Koutakis: Research Grant; Significant; American Heart Association Post-Doctoral Fellowship 15POST25520004. H. Hernandez: None. J.R. Thompson: None. E. Papoutsi: None. H.K. DeSpiegelaere: None. D. Miserlis: None. G. Haynatzki: None. D.M. Ha: None. C.J. Mietus: None. J. Kim: None. Z. Zhu: None. G.P. Casale: None. I.I. Pipinos: None.
- © 2016 by American Heart Association, Inc.