# Weight loss and exercise to improve rheumatoid arthritis cardiovascular risk

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $147,312

## Abstract

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.

## Key facts

- **NIH application ID:** 10663627
- **Project number:** 3R21AR076663-02S1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** KIM M. HUFFMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $147,312
- **Award type:** 3
- **Project period:** 2020-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10663627

## Citation

> US National Institutes of Health, RePORTER application 10663627, Weight loss and exercise to improve rheumatoid arthritis cardiovascular risk (3R21AR076663-02S1). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/10663627. Licensed CC0.

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