Weight loss and exercise to improve rheumatoid arthritis cardiovascular risk

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Despite recent, revolutionary improvements in pharmacologic management, rheumatoid arthritis (RA) remains associated with increased rates of cardiovascular disease and mortality. RA cardiovascular risk results from a combination of traditional risk factors and RA-related systemic inflammation. Consequently, to improve overall RA cardiovascular risk, efforts should target both traditional risk factors and inflammation. One hypothetical means of improving overall RA cardiovascular risk is through weight loss and physical activity. Together, weight loss and physical activity can improve traditional cardiometabolic health through fat mass loss and skeletal muscle quality and functional gains. Additionally, disease-related cardiovascular risk will improve as both fat mass loss and exercise reduce systemic inflammation. To explore this hypothesis, 26 older, overweight to obese persons with RA will be randomized to a control intervention based on traditional clinical counselling or to a supervised weight loss plus exercise training program (3 times per week). Weight loss will occur via a dietitian-led intervention targeting 7% weight loss over 16 weeks, with weekly weigh-ins and group support sessions. Exercise training will consist of three times per week of an interval-based aerobic program plus twice-weekly resistance training. Both weight loss and exercise training will be supervised to maximize safety and adherence. The primary cardiometabolic outcome is a highly validated metabolic syndrome z-score, calculated from blood pressure, waist circumference, HDL-cholesterol, triglycerides, and glucose. RA-related cardiovascular risk will be assessed with measures of systemic inflammation, RA disease activity, and macrophage function – key cells at the nexus of rheumatic and cardiovascular disease activity. Intervention impacts on self-reported outcomes will be assessed with validated measures from the Patient Reported Outcomes Measurement Information System (PROMIS). This exploratory clinical trial will show whether a supervised intervention with weight loss and exercise training improves objective assessments of RA cardiovascular risk, disease activity and results in patients reporting overall improved health. This investigation will establish feasibility, acceptance, compliance, fidelity, and generate effects sizes critical for designing larger RA interventions, especially those comparing weight loss and physical activity amounts and types. Also, by demonstrating that weight loss with physical activity not only improves RA-associated cardiovascular risk and disease activity, but also patient-reported global health, this work should provide immediate and long-lasting impacts on RA clinical care.