# Weight loss and exercise to improve rheumatoid arthritis cardiovascular risk

> **NIH NIH R21** · DUKE UNIVERSITY · 2021 · $274,859

## 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, 44 older, 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:** 10190841
- **Project number:** 5R21AR076663-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** KIM M. HUFFMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $274,859
- **Award type:** 5
- **Project period:** 2020-06-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190841

## Citation

> US National Institutes of Health, RePORTER application 10190841, Weight loss and exercise to improve rheumatoid arthritis cardiovascular risk (5R21AR076663-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10190841. Licensed CC0.

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