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Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

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Abstract

The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p < 0.001), intercellular cell adhesion molecule-1 (ICAM-1) (p < 0.001), diabetes (p = 0.003), sex (p = 0.003), and history of cerebrovascular accidents (p = 0.021). In multivariate analyses for gait cadence, the significant independent predictors included high-sensitivity C-reactive protein (HsCRP) (p < 0.001), diabetes (p = 0.001), and hypertension (p = 0.001). In a multivariate regression model for gait stride length, the significant independent variables were HsCRP (p < 0.001), age (p < 0.001), ICAM-1 (p < 0.001), hypertension (p = 0.002), cellular reactive oxygen species production (p = 0.007), and sex (p = 0.008). Higher levels of circulating biomarkers of inflammation and endothelial cell oxidative stress were associated with slower gait speed, slower cadence, and shorter stride length in older symptomatic patients with PAD. Additionally, this profile of impaired gait was more evident in older patients, in women, and in those with diabetes, hypertension, and history of cerebrovascular accidents.

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Acknowledgments

The study is supported by grants from the National Institute on Aging (R01-AG-24296 to AWG; AG031085 to AC), Oklahoma Center for the Advancement of Science and Technology (to AWG, AC, and ZU), and General Clinical Research Center (M01-RR-14467), the American Heart Association (to AC and ZU), and the National Center for Complementary and Alternative Medicine (R01-AT006526 to ZU).

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Authors and Affiliations

  1. Reynolds Oklahoma Center on Aging, Donald W. Reynolds Department of Geriatric Medicine, University of Oklahoma Health Sciences Center (OUHSC), 1122 N.E. 13th Street, O’Donoghue Research Building, Suite 1200, Oklahoma City, OK, 73117, USA

    Andrew W. Gardner, Polly S. Montgomery, Zoltan Ungvari & Anna Csiszar

  2. Cardiovascular Section, Department of Medicine, OUHSC, Oklahoma City, OK, USA

    Ana I. Casanegra & Federico Silva-Palacios

  3. Veterans Affairs Medical Center, Oklahoma City, OK, USA

    Andrew W. Gardner

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  1. Andrew W. Gardner
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  2. Polly S. Montgomery
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  3. Ana I. Casanegra
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  4. Federico Silva-Palacios
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  5. Zoltan Ungvari
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  6. Anna Csiszar
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Correspondence to Andrew W. Gardner.

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Gardner, A.W., Montgomery, P.S., Casanegra, A.I. et al. Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease. AGE 38, 64 (2016). https://doi.org/10.1007/s11357-016-9925-y

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