- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
Until recently, most studies of body composition in rheumatoid arthritis (RA) have focused on low lean mass or cachexia that may be caused by chronic inflammation (1, 2). However, newer studies suggest that a substantial portion of individuals with RA may be obese or overfat (3–5), which may in part explain the increased cardiovascular (CV) disease risk seen in RA. Visceral fat appears to carry the greatest CV risk (6–8), and a high prevalence of central or abdominal obesity has been found in RA (9, 10). The strong association between central obesity and CV outcomes suggests that waist circumference (WC), often used as a proxy measure for central obesity or visceral fat mass, may be useful in RA, but this has not been confirmed.
In most large-scale studies, obesity is estimated from body mass index (BMI; weight [kg]/height [m2]). BMI may not accurately reflect the amount of body fat in persons with RA (4, 9), however, because rheumatoid cachexia may occur with little or no weight loss; therefore, an individual may have a BMI within a normal range, but may have greater fat mass than suggested by the BMI. As an example, one recent study reported that ∼33% of an RA cohort was obese by BMI, a proportion that is approximately equivalent to the proportion of obesity in the general population (5). Yet, using a more sensitive measure of body composition, more than one-half of this same sample was resolutely overfat. Use of RA-specific BMI criteria for defining obesity has been suggested (4), but little validation of revised BMI criteria has occurred.
Additionally, there is preliminary evidence of sex differences in the impact of RA on body composition. Giles et al reported that women with RA had significantly greater total body fat than women in a BMI-matched control group, but no differences in total fat were noted between men with RA and male controls (5). Perhaps most important, however, is that men with RA appeared to accumulate greater visceral fat (10).
The goals of these analyses were to 1) determine the proportion of a cohort of men and women with RA who were obese using dual x-ray absorptiometry (DXA) and 2 common anthropometric proxy measures, BMI and WC; 2) evaluate the accuracy of the standard obesity criteria for anthropometric measures for men and women with RA compared to DXA determinations of obesity, and identify criteria that best reflect DXA results; and 3) examine the association of body fat and obesity with measures of RA symptoms and disease activity and CV risk.
Significance & Innovations
Obesity is associated with numerous negative health effects, including heightened cardiovascular risk.
The prevalence of obesity is high in rheumatoid arthritis (RA); there appear to be substantial sex differences in prevalence, with obesity more common in men than in women with RA.
Obesity defined by anthropometric proxy measures identifies poor RA-specific outcomes, as well as cardiovascular risk.
Lower, sex-specific cut points to define obesity by both body mass index and waist circumference may be warranted.
- Top of page
- PATIENTS AND METHODS
- AUTHOR CONTRIBUTIONS
A large portion of this RA sample was obese, including more than one-quarter using the standard BMI definition, one-third using the standard WC definitions, and more than one-half using percent fat from DXA. These rates are similar to those reported in other RA samples, e.g., Giles et al reported that 33% of women and 36% of men with RA were obese by BMI and 57% were obese by DXA (5), and a UK study reported a BMI-defined prevalence of obesity of 31% (37).
Differences between rates of obesity in men and women were striking. Using both BMI and DXA criteria, twice as many men as women were classified as obese. DXA results showed that 80% of men in this RA sample were overfat. Of particular note, there was no significant difference in the total percent fat between men and women in our sample, a finding that is at odds with population studies (38, 39). Other published studies have noted differences in adiposity between men and women with RA. For example, Giles et al found that abdominal visceral adiposity was 51% higher in men with RA compared to men without RA, whereas there was no difference between women with and without RA (10). On the other hand, women with RA had more subcutaneous abdominal fat. Stavropoulos-Kalinoglou et al also noted relatively higher fat distributions in men with RA compared to men without RA (4). Men with RA had total fat percentages 49% higher than controls, while total percent fat for women with RA was 19% higher than controls. For truncal fat, men with RA were 43% higher than controls, while women with RA were 23% higher than controls. However, none of these studies reported disparities in the prevalence of obesity between men and women with RA of the size that we found. Additional research with larger samples will be needed to clarify this unexpected finding.
We identified much lower BMI criteria to define obesity, as well as different criteria for men and women (≥24.7 kg/m2 for men and ≥26.1 kg/m2 for women). Stavropoulos-Kalinoglou et al previously suggested that the BMI cut point for obesity be reduced by 2 kg/m2 (i.e., to 28 kg/m2) for individuals with RA; our analyses support cut points that are even lower. Other investigators have also noted that the current obesity cut point of a BMI ≥30 kg/m2 in non-RA populations is too high, has low sensitivity to detect adiposity in the general population, and is not appropriate for specific ethnic groups, and have identified alternate BMI obesity cut points very similar to those we identified, ranging from 25–25.8 kg/m2 (40–45).
Relationships between DXA body fat measures and RA disease status measures existed for both men and women. Greater total percent fat was associated with higher pain ratings, higher disease activity ratings, and greater fatigue for men and women. Greater truncal fat was also associated with higher pain ratings and greater fatigue for both men and women. Framingham risk scores were associated with DXA-defined obesity and truncal fat for women, but not for men. Among women, inflammatory biomarkers were also associated with percent truncal fat; a similar association was not noted for men. There were few nonobese men, however, which may have limited our ability to find these associations, although Giles et al also noted different patterns of the association of fat with CRP level for men and women (22); adiposity was significantly associated with CRP level for women, but not for men, which is similar to our findings.
We expected the associations between anthropometric obesity proxies and RA disease status and CV risk measures to parallel those seen with measures of body fatness obtained through DXA, and there were important consistencies as well as inconsistencies. BMI appeared to function satisfactorily as a proxy for DXA-derived obesity in these analyses. Men and women who met the standard BMI obesity criterion had significantly greater pain, disease activity, fatigue, and ESRs. Only a few associations were noted with the revised BMI criterion, calling its usefulness into question.
The revised WC cut points improved correspondence with DXA over the original WC cut points, but only marginally. Substantial differences existed between men and women in the associations between central obesity and RA disease measures. There were no significant differences in RA disease measures for men using either WC criterion. In contrast, women who met the original WC obesity criterion exhibited worse RA status on all measures, and differences remained for pain, the RADAI, and fatigue when the revised WC criterion was used.
The relationship between WC and CV risk was more robust. Both men and women who met either WC obesity criterion had significantly higher Framingham risk scores. The revised WC definitions we derived are similar to those proposed by the International Diabetes Federation (46) for whites at low risk for metabolic syndrome (94 cm for men and 80 cm for women). Further research is needed to establish the usefulness of WC as a proxy of obesity in RA and the appropriate criteria to define obesity.
Our revised obesity criteria for both BMI and WC improved sensitivity to detect obesity over the traditional definitions, but decreased specificity. Since BMI and WC might be used as screening tests to identify individuals with potentially harmful levels of body fat, a condition treatable by fairly benign means but associated with a heightened risk of a number of poor health outcomes, the tradeoff of high sensitivity for lower specificity, particularly when specificity is still at an acceptable level, seems appropriate.
This study has several limitations. The sample was relatively small, and we may have lacked statistical power in some cases. These analyses present cross-sectional associations; no causal attributions can be made. Clearly, these analyses need to be repeated with larger, longitudinal samples. The range of disease severity may have limited our findings. Few participants had very active RA, but the restricted range of disease activity should have biased our findings toward the null. Population-based studies have demonstrated racial and ethnic differences in the correspondence of BMI with body fatness. Our sample was primarily white, which limits the extent to which our results, particularly the revised obesity definitions, can be extended to other groups; at the same time, however, our more homogenous sample limited the variability due to racial or ethnic differences. We have only measures of total truncal fat, and were not able to differentiate between subcutaneous and visceral fat. Sex differences in the preponderance of visceral fat have previously been noted in an RA sample, with men having greater visceral fat, and visceral fat is, in turn, most strongly linked to CV events and outcomes (6–8). Glucocorticoid use has often been linked to body composition; cumulative prednisone dose has been linked to visceral fat (10, 47). While we were able to control for glucocorticoid use during the year prior to data collection, we do not have a good estimate of cumulative glucocorticoid use.
Our results do not provide a clear picture of the mechanism whereby obesity might be associated with worse RA disease or CV risk, although we can make a proposal based on analyses of the inflammatory biomarker results. Elevated ESR is often linked to active or severe RA; likewise, elevated CRP level is associated with a longitudinal risk of CV disease. It seems reasonable to project that greater amounts of adipose tissue are a source of inflammation, which then may lead to heightened disease activity and CV risk (3, 22, 48–50). This mechanism has been proposed by several investigators and our cross-sectional associations provide supportive evidence, but future longitudinal studies are needed to further elucidate these pathways. While a paradoxical relationship has been found in which obesity is associated with less severe joint damage in RA, other health effects of obesity in RA appear to parallel those seen in the general population, i.e., increased CV risk, greater functional limitations, and worse disease status.
These findings provide further evidence of a high prevalence of obesity or overfatness among individuals with RA. Sex differences existed in this sample, with men having higher rates of obesity, which may place them at a particularly high risk of CV disease and events. Findings from this study indicate that consideration of separate BMI obesity criteria for men and women may be warranted, although this proposal should be confirmed in other samples. The revised BMI and WC cut points identified for women with RA are very similar to those identified for women with systemic lupus erythematosus using the same methodology (BMI: 26.8 kg/m2, WC: 84.75 cm) (51). Nonetheless, these revised obesity criteria may be overly stringent; those suggested by Stavropoulos-Kalinoglou et al (BMI ≥28 kg/m2) (4) may be more realistic. However, these results do underscore the issue of importance of considering overfatness in RA.
Future research is needed to determine if the relationships noted in these 2 rheumatic conditions are unique, if lower obesity criteria should be considered for connective tissue diseases in general, or if these lower cut points are reflective of changes in body composition in the general population. Regardless, these results suggest that use of more stringent criteria for proxy measures such as BMI among individuals with RA, as has been previously suggested, may be warranted, since more stringent methods appear to identify risk for poor RA outcomes as well as heightened CV risk. Furthermore, anthropometric measures may provide proxy estimates of body composition that are as effective in identifying risk for poor RA and CV outcomes as DXA, but are much less costly and can easily be implemented in clinical settings.