The outlook for patients with rheumatoid arthritis (RA) has improved dramatically in the last decade with the advent of combination therapies and novel biologic targeted therapies. Earlier diagnosis and intervention has also resulted in less severe joint damage and a decrease in long-term disability. These advances mean improved quality of life for patients with RA, better health outcomes, and possibly a decreased risk of cardiovascular disease.
But suppose that even with these improvements, doctors are missing a key clinical factor—a modifiable factor—in the management of RA. Joan Bathon, MD, professor of medicine and deputy director of the division of rheumatology at Johns Hopkins Medical Institution in Baltimore, Md., believes this might, in fact, be the case. That’s why Dr. Bathon and her colleagues are studying the connection between RA and body composition in research funded by the ACR Research and Education Foundation (REF). “We know that RA patients have reduced muscle mass and an increase in fat mass,” says Dr. Bathon. “What we don’t know is what effects this adverse body composition phenotype is having on important health outcomes like cardiovascular disease.”
An increase in body fat, especially visceral fat in the abdomen, may lead to higher rates of cardiovascular disease, including heart attack and stroke, and higher rates of death from these events, says Dr. Bathon. “Too little muscle and too much fat is a double whammy when it comes to a level of function,” she notes. Both are disabling in the general population because having too little muscle makes it difficult for the person to walk, lift objects, and do daily tasks. When the person gains weight from a lack of exercise, his or her daily activities are often further decreased. But, stresses Dr. Bathon, losing weight in these circumstances isn’t the sole answer because a general loss of weight results in a loss of muscle as well. “The key is a combination of weight loss with muscle building,” she says.
Dr. Bathon’s research goal is to investigate the association of adverse body composition in RA patients with overall health outcomes. The results of the analysis will prove important in the clinical practice setting for rheumatologists, she adds.
Dr. Bathon’s latest work on body composition and RA shows how the REF funding is leveraging research that is already underway. Her REF grant is funded through the Within Our Reach: Finding a Cure for Rheumatoid Arthritis campaign, which supports RA research that is not being done anywhere else. The grant is allowing Dr. Bathon and her Johns Hopkins colleague, Jon Giles, MD, assistant professor of medicine there, to go beyond preliminary work funded by the National Institutes of Health. Their research, the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis (ESCAPE-RA), is a five-year cohort study. The goal of ESCAPE-RA is to identify risk factors for prevalent and progressive subclinical cardiovascular disease in subjects with RA—and it provides the patient population needed to study body composition in RA and relate it to important health outcomes.
“The fact that [the REF] is stepping up to allow us to roll the body composition studies into an ongoing study in which the cohort is already assembled, and important outcome data is already being collected, is an efficient and less expensive way to study this important but poorly studied clinical problem in rheumatoid arthritis,” says Dr. Bathon.
Study Specifics
The REF award of $400,000 is funding research on body composition in RA patients for two years—from July 2007 to June 2009. These studies are incorporated into the third and final visit of the ESCAPE-RA study. Dr. Bathon says findings from her latest study may well be significant in the day-to-day treatment and management of RA patients. “The findings are particularly important because body composition is a modifiable risk factor,” she stresses. “Our ongoing studies will hopefully clarify the contribution of the adverse body composition phenotype to cardiovascular risk, disability, and joint damage, and will lay the groundwork for clinical recommendations and interventions to identify and reverse adverse body composition phenotypes, in order to reduce morbidity and mortality in RA.” The overall hypothesis is that RA patients have an adverse body composition profile, which is an independent contributor to poor health outcomes in RA.
The REF-funded study involves 196 participants with RA who previously enrolled in ESCAPE-RA. The cohort consists of 118 women and 78 men who have no prior self-reported, physician-diagnosed clinical cardiovascular event. The study includes three visits, with the following data collected at each visit:
- Cardiovascular history;
- RA history;
- Medical history;
- Medications;
- Physical activity;
- Diet;
- Psychosocial factors;
- Extra-articular disease; and
- Family history.
The physical exam consists of vital signs, anthropometry (weight, height, body mass index, and waist and hip circumference), and 48-joint assessment for tenderness, swelling, malalignment, and range of motion. At the first and third visits, cardiac CT scans for coronary artery calcium are obtained. Carotid ultrasound was funded in the ESCAPE study for the first visit and will be repeated at the third visit using the REF funds. Total body DXA scans as well as abdominal and mid-thigh CT scans likewise will be added at the third visit through the REF grant. Coronary artery calcium and carotid plaque and intima-media thickness will be used as surrogate measures of atherosclerotic plaque in study participants. Other measures include the short Physical Performance Battery to measure physical function and disability, radiographic assessment of joint damage, the disease activity score for 28 joints, C-reactive protein, self-reported habitual physical activity assessment using a seven-day questionnaire, and a composite score to assess cardiovascular risk.
The hypotheses for this study are:
- Patients with RA will have a higher total fat mass and lower total lean mass, a higher regional mass (in abdominal visceral and thigh deposits), a higher leptin and resistin and lower adiponectin level even after adjustment for differences in levels of physical activity, and inflammatory markers; and
- Compared with patients with RA with a favorable body composition profile, patients with RA with adverse body composition profile will have a higher prevalence of subclinical atherosclerosis, lower physical function, more disability, and more articular damage.
Future Trials
If these hypotheses are proven, Dr. Bathon says the next step would be a clinical trial that addresses modification of body composition. The exact design for a future study will depend on the primary goal. If the goal is to reduce the risk of cardiovascular events, then modifying body composition to a more favorable phenotype through diet and exercise should be combined with aggressive control of other risk factors, such as a tight control of lipids, glucose, and blood pressure.
There is increasing evidence to suggest that cardiovascular risk in RA patients may also be lowered via tight control of RA disease activity. “These two approaches would have to be combined somehow and such an algorithm would be complex,” she says. “The results of the current study will inform the development of clinical strategies to prevent or reverse adverse body composition, and will set the stage for the conduct of clinical trials to investigate the efficacy of modifying body composition on morbidity and mortality in RA.”
Terry Hartnett is a medical journalist based in Pittsburgh.