Study Design, Rationale, and Methodology for Promote Weight Loss in Patients With Peripheral Artery Disease Who Also Have Obesity: The PROVE Trial.

Background Overweight and obesity are associated with adverse functional outcomes in people with peripheral artery disease (PAD). The effects of weight loss in people with overweight/obesity and PAD are unknown. Methods The PROVE (Promote Weight Loss in Obese PAD Patients to Prevent Mobility Loss) Trial is a multicentered randomized clinical trial with the primary aim of testing whether a behavioral intervention designed to help participants with PAD lose weight and walk for exercise improves 6-minute walk distance at 12-month follow-up, compared with walking exercise alone. A total of 212 participants with PAD and body mass index ≥25 kg/m2 will be randomized. Interventions are delivered using a Group Mediated Cognitive Behavioral intervention model, a smartphone application, and individual telephone coaching. The primary outcome is 12-month change in 6-minute walk distance. Secondary outcomes include total minutes of walking exercise/wk at 12-month follow-up and 12-month change in accelerometer-measured physical activity, the Walking Impairment Questionnaire distance score, and the Patient-Reported Outcomes Measurement Information System mobility questionnaire. Tertiary outcomes include 12-month changes in perceived exertional effort at the end of the 6-minute walk, diet quality, and the Short Physical Performance Battery. Exploratory outcomes include changes in gastrocnemius muscle biopsy measures of mitochondrial cytochrome C oxidase activity, mitochondrial biogenesis, capillary density, and inflammatory markers. Conclusions The PROVE randomized clinical trial will evaluate the effects of exercise with an intervention of coaching and a smartphone application designed to achieve weight loss, compared with exercise alone, on walking performance in people with PAD and overweight/obesity. Results will inform optimal treatment for the growing number of patients with PAD who have overweight/obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04228978.

Cumulative strain-based metrics for predicting subconcussive head impact exposure-related imaging changes in a cohort of American youth football players.

OBJECTIVE: Youth football athletes are exposed to repetitive subconcussive head impacts during normal participation in the sport, and there is increasing concern about the long-term effects of these impacts. The objective of the current study was to determine if strain-based cumulative exposure measures are superior to kinematic-based exposure measures for predicting imaging changes in the brain. METHODS: This prospective, longitudinal cohort study was conducted from 2012 to 2017 and assessed youth, male football athletes. Kinematic data were collected at all practices and games from enrolled athletes participating in local youth football organizations in Winston-Salem, North Carolina, and were used to calculate multiple risk-weighted cumulative exposure (RWE) kinematic metrics and 36 strain-based exposure metrics. Pre- and postseason imaging was performed at Wake Forest School of Medicine, and diffusion tensor imaging (DTI) measures, including fractional anisotropy (FA), and its components (CL, CP, and CS), and mean diffusivity (MD), were investigated. Included participants were youth football players ranging in age from 9 to 13 years. Exclusion criteria included any history of previous neurological illness, psychiatric illness, brain tumor, concussion within the past 6 months, and/or contraindication to MRI. RESULTS: A total of 95 male athletes (mean age 11.9 years [SD 1.0 years]) participated between 2012 and 2017, with some participating for multiple seasons, resulting in 116 unique athlete-seasons. Regression analysis revealed statistically significant linear relationships between the FA, linear coefficient (CL), and spherical coefficient (CS) and all strain exposure measures, and well as the planar coefficient (CP) and 8 strain measures. For the kinematic exposure measures, there were statistically significant relationships between FA and RWE linear (RWEL) and RWE combined probability (RWECP) as well as CS and RWEL. According to area under the receiver operating characteristic (ROC) curve (AUC) analysis, the best-performing metrics were all strain measures, and included metrics based on tensile, compressive, and shear strain. CONCLUSIONS: Using ROC curves and AUC analysis, all exposure metrics were ranked in order of performance, and the results demonstrated that all the strain-based metrics performed better than any of the kinematic metrics, indicating that strain-based metrics are better discriminators of imaging changes than kinematic-based measures. Studies relating the biomechanics of head impacts with brain imaging and cognitive function may allow equipment designers, care providers, and organizations to prevent, identify, and treat injuries in order to make football a safer activity.

Elevated IL-6 and CRP Levels Are Associated With Incident Self-Reported Major Mobility Disability: A Pooled Analysis of Older Adults With Slow Gait Speed.

BACKGROUND: Elevated interleukine-6 (IL-6) and C-reactive protein (CRP) are associated with aging-related reductions in physical function, but little is known about their independent and combined relationships with major mobility disability (MMD), defined as the self-reported inability to walk a quarter mile. METHODS: We estimated the absolute and relative effect of elevated baseline IL-6, CRP, and their combination on self-reported MMD risk among older adults (≥68 years; 59% female) with slow gait speed (<1.0 m/s). Participants were MMD-free at baseline. IL-6 and CRP were assessed using a central laboratory. The study combined a cohort of community-dwelling high-functioning older adults (Health ABC) with 2 trials of low-functioning adults at risk of MMD (LIFE-P, LIFE). Analyses utilized Poisson regression for absolute MMD incidence and proportional hazards models for relative risk. RESULTS: We found higher MMD risk per unit increase in log IL-6 (hazard ratio [HR] = 1.26; 95% confidence interval [95% CI] 1.13-1.41). IL-6 meeting predetermined threshold considered to be high (>2.5 pg/mL) was similarly associated with higher risk of MMD (HR = 1.31; 95% CI 1.12-1.54). Elevated CRP (CRP >3.0 mg/L) was also associated with increased MMD risk (HR = 1.38; 95% CI 1.10-1.74). The CRP effect was more pronounced among participants with elevated IL-6 (HR = 1.62; 95% CI 1.12-2.33) compared to lower IL-6 levels (HR = 1.19; 95% CI 0.85-1.66). CONCLUSIONS: High baseline IL-6 and CRP were associated with an increased risk of MMD among older adults with slow gait speed. A combined biomarker model suggests CRP was associated with MMD when IL-6 was elevated.

Association of Fish Oil and Physical Activity on Mobility Disability in Older Adults.

PURPOSE: This study aimed to examine whether long-term fish oil (FO) supplementation is associated with a lower risk of mobility disability and enhances benefits of physical activity (PA). METHODS: A total of 1635 sedentary adults age 70 to 89 yr from the Lifestyle Interventions and Independence for Elders single-blinded randomized, multicenter clinical trial, which compared a structured PA program to a health education program. Primary outcome was incident major mobility disability (MMD), defined by loss of ability to walk 400 m, measured every 6 months for an average of 2.6 yr. Secondary outcomes included persistent mobility disability, Short Physical Performance Battery, 400-m walk speed, and grip strength. RESULTS: A third of participants reported using FO at baseline (456 (28%); mean age, 78.5 yr; 70.5% women). MMD was experienced by 131 participants (28.7%) in the FO group and 405 (34.4%) participants in the nonuser group. After adjusting for confounders, FO supplementation was associated with a lower risk (HR, 0.78; 95% confidence interval (CI), 0.64-0.96) of incident MMD. However, there was no interaction (P = 0.19) between FO supplementation and PA intervention for MMD. For the secondary outcome of persistent mobility disability, the intervention association differed by supplementation (P = 0.002) with PA intervention associations of (HR, 1.36; 95% CI, 0.83-2.23) for users and (HR, 0.61; 95% CI, 0.46-0.81) for nonusers. Changes in physical performance outcomes were not modified by baseline FO supplementation or combination with PA. CONCLUSIONS: FO supplementation was associated with a lower risk of MMD in low to moderate functioning older adults. However, supplementation did not enhance the benefit of PA on risk of mobility disability. These results are hypothesis generating and need to be confirmed in randomized trials.

Effect of Losartan and Fish Oil on Plasma IL-6 and Mobility in Older Persons. The ENRGISE Pilot Randomized Clinical Trial.

BACKGROUND: Low-grade chronic inflammation, characterized by elevations in plasma Interleukin-6 (IL-6), is an independent risk factor of impaired mobility in older persons. Angiotensin receptor blockers and omega-3 polyunsaturated fatty acids (ω-3) may reduce IL-6 and may potentially improve physical function. To assess the main effects of the angiotensin receptor blocker losartan and ω-3 as fish oil on IL-6 and 400 m walking speed, we conducted the ENRGISE Pilot multicenter randomized clinical trial. METHODS: The ENRGISE Pilot enrolled participants between April 2016 and June 2017, who participated for 12 months. Participants were aged ≥70 years with mobility impairment, had IL-6 between 2.5 and 30 pg/mL, and were able to walk 400 m at baseline. Participants were randomized in three strata 2 × 2 factorial to: (i) losartan 50-100 mg/d or placebo (n = 43), (ii) fish oil 1,400-2,800 mg/d or placebo (n = 180), and (iii) with both (n = 66). RESULTS: Two hundred eighty-nine participants were randomized (mean age 78.3 years, 47.4% women, 17.0% black). There was no effect of losartan (difference of means = -0.065 ± 0.116 [SE], 95% confidence interval [CI]: -0.293-0.163, p = .58) or fish oil (-0.020 ± 0.077, 95% CI: -0.171-0.132, p = .80) on the log of IL-6. Similarly, there was no effect of losartan (-0.025 ± 0.026, 95% CI: -0.076-0.026, p = .34) or fish oil (0.010 ± 0.017, 95% CI: -0.025-0.044, p = .58) on walking speed (m/s). CONCLUSIONS: These results do not support the use of these interventions to prevent mobility loss in older adults at risk of disability with low-grade chronic inflammation. REGISTRATION: Clinicaltrials.gov NCT02676466.

Change in health-related quality of life and social cognitive outcomes in obese, older adults in a randomized controlled weight loss trial: Does physical activity behavior matter?

This article compared the effect of dietary weight loss administered alone (WL) or in combination with aerobic training (WL + AT) or resistance training (WL + RT) on health related quality of life, walking self-efficacy, stair climb self-efficacy, and satisfaction with physical function in older adults with cardiovascular disease or the metabolic syndrome. Participants (N = 249; M age = 66.9) engaged in baseline assessments and were randomly assigned to one of three interventions, each including a 6-month intensive phase and a 12-month follow-up. Those in WL + AT and WL + RT engaged in 4 days of exercise training weekly. All participants engaged in weekly group behavioral weight loss sessions with a goal of 7-10% reduction in body weight. Participants in WL + AT and WL + RT reported better quality of life and satisfaction with physical function at 6- and 18-months relative to WL. At month 6, WL + AT reported greater walking self-efficacy relative to WL + RT and WL, and maintained higher scores compared to WL at month 18. WL + AT and WL + RT reported greater stair climbing efficacy at month 6, and WL + RT remained significantly greater than WL at month 18. The addition of either AT or RT to WL differentially improved HRQOL and key psychosocial outcomes associated with maintenance of physical activity and weight loss. This underscores the important role of exercise in WL for older adults, and suggests health care providers should give careful consideration to exercise mode when designing interventions.

Changes in body composition over 8 years in a randomized trial of a lifestyle intervention: the look AHEAD study.

OBJECTIVE: To determine the effects of an intensive lifestyle intervention versus a comparison group on body composition in obese or overweight persons with type 2 diabetes at baseline and at 1, 4, and 8 years. METHODS: Body composition was measured by dual-energy X-ray absorptiometry in a subset of 1019 Look AHEAD study volunteers randomized to intervention or comparison groups. The intervention was designed to achieve and maintain ≥7% weight loss through increased physical activity and reduced caloric intake. The comparison group received social support and diabetes education. RESULTS: At 1 year, the intervention group lost fat (5.6 ± 0.2 kg) and lean mass (2.3 ± 0.1 kg) but regained fat (∼100%) and lost lean mass between years 1 and 8. Between baseline and year 8, weight loss was greater in intervention versus comparison groups (4.0 ± 0.4 vs. 2.3 ± 0.4 kg); comparison group weight loss was mostly lean mass (2.1 ± 0.17 kg). Fat mass in the intervention group was lower than that of the comparison group at all post-baseline time points. CONCLUSIONS: Reduced fat mass may place the intervention group at a lower risk of obesity-linked sequelae, a hypothesis that can be tested by future studies of this cohort.