What Effect Does BMI Have on Mortality in Patients with Rheumatoid Arthritis
Body weight changes have been a recognized feature of rheumatoid arthritis (RA) for over 100 years. The spectrum of body weight changes in RA can include frank wasting, termed rheumatoid cachexia, in which the degree of wasting (primarily of skeletal muscle) correlates with the intensity of systemic inflammation. In the general population, extremes of body weight (both high and low) are associated with increased mortality. Recently, an association between low body mass index (BMI: weight/height2) and cardiovascular mortality in RA was published (Kremers et al. Arthritis Rheum 2004; 50: 3450). However, the association of BMI and all-cause mortality in RA has not been explored. Here, Escalante et al (Arch Intern Med 2005; 165: 1624) examine the effect of BMI on mortality in a prospective outpatient clinic-based cohort of RA patients.
Results: 779 patients were followed for a total of 3460 patient-years. 71% of patients were female. At intake, 38 (5%) were classified as underweight (BMI < 20), 195 (25%) were normal weight (BMI of 20 to <25), 264 (34%) were overweight (BMI 25 to <30), and 282 (36%) were obese (BMI >30). Obese patients tended to be younger at baseline than underweight patients (mean age 52 vs. 63 years, respectively) with shorter disease duration (9 vs. 15 years, respectively) and fewer deformed joints (7 vs. 18 joints, respectively). In addition, obese patients were more likely to be Hispanic, less likely to be White, and of lower socio-economic status.
123 patients died during the study period, corresponding to a crude death rate of 3.6 per 1000 person-years. BMI specific death rates were the highest among underweight patients and declined with increasing BMI. This relationship persisted after adjusting for age and sex.
| BMI strata | Unadjusted death rate (per 1000 person years) |
Age- and gender-adjusted death rate (per 1000 person years) |
| Underweight | 15.0 | 6.8 |
| Normal weight | 5.4 | 3.3 |
| Overweight | 3.3 | 2.1 |
| Obese | 1.7 | 1.4 |
Further, mortality in the patients with the highest BMI (>35) compared to normal weight was not significantly different from those with BMI between 30 and 35. A 9% reduction in mortality risk was observed for each unit increase in BMI, an effect independent of age of RA onset, disease duration, gender, ethnicity, socio-economic status, use of methotrexate, or smoking. Similarly, each 10mm/hr increase in ESR was associated with a 15% increase in mortality. Accounting for comorbid illness and RA disease severity diminished the effect of BMI and cancelled the effect of ESR on mortality in these models.
When the interaction between ESR and BMI was modeled, patients with the highest BMI and lowest ESR showed the greatest survival benefit. High ESR (top two-fifths of distribution) negated the protective effect of high BMI on survival.
Conclusions: Mortality rates decrease with increasing BMI in RA, with obese RA patients having the lowest mortality rate. This effect is modified by inflammation, RA severity, and comorbid disease.
Editorial Comment: The biggest surprise from these findings is not so much that the lowest BMI was associated with increased mortality, but that increasing BMI conferred a survival benefit for obese RA patients over those of normal weight. The basis for this seemingly paradoxical effect is not apparent here, although its effect appears to be strongly associated with degree of inflammation, disease severity, and comorbid disease. For patients without RA, the benefit of having a slightly elevated BMI appears to be related to possessing some stored reserve for times of sickness (such as during an acute hospitalization in the elderly) when catabolic rate is increased. RA, particularly in its most active inflammatory stages, is associated with increased catabolic rate and thus, higher BMI (which may translate not only to a greater amount of body fat, but also to more metabolically vital muscle) may be a marker of metabolic reserve. In addition, it has been recently established that certain fat storage areas in women, such as the hips and buttocks, may actually be protective against cardiovascular disease and cardiovascular death. In this setting, BMI alone cannot establish what changes are occurring in fat and muscle composition that may be associated with higher or lower mortality.
Finally, it should be noted that although the very obese patients of this study tended to have lower mortality rates than both the underweight or normal weight patients, there is no comparison to a non-RA population. In general, age-adjusted mortality rates for RA patients are higher than those of non-RA patients as in the study by Kremers et al (cited above) in which cardiovascular mortality in RA patients was increased at all BMI levels compared to non-RA controls, albeit most pronounced for patients who at any point had dipped into the underweight category.
