Cardiovascular Events in Rheumatoid Arthritis—Time to See Beyond Articular Involvement in “Real World” Clinical Practice: Comment on the Article by Mackey et al

highly important risk factor for early death in RA. Because of the dynamic effects of weight over time and their relationship to disease activity and comorbid conditions, it is important to note that epidemiologic studies to date that have assessed associations between body mass and mortality are likely to have systematically underestimated the causal risks of obesity in RA. Gremese et al appropriately distinguish between intentional and unintentional weight loss. We fully agree that while unintentional weight loss is hypothesized to be predictive of death, intentional weight loss would, in contrast, be hypothesized to be protective. Unfortunately in a large database study it is rarely possible to make this distinction. Fortunately, however, there are data from other populations within this age group suggesting that .60% of weight loss is unintentional (1–3), and in these previous studies, unintentional weight loss was associated with greater mortality but intentional weight loss was not. Therefore, it is likely that the associations between weight loss and death observed in our study are most representative of the risk posed by unintentional weight loss. We hope to further emphasize that overall, these observations should further support aims to promote intentional weight loss among patients with RA: there is no evidence to suggest that intentional weight loss would have anything but positive effects on health. We also agree with Gremese and colleagues that weight loss is likely linked to disease activity over time. In fact, in studies published by us (using data from the same cohort) (4) and by others (1), it has been demonstrated that higher CRP levels and less improvement in these levels are associated with greater weight loss. While some analyses in our study were performed after adjustment for time-varying measures of CRP and other factors (4), we would not suggest that weight loss is itself causally associated with mortality risk. However, there is strong evidence that weight loss is an important timedependent confounder between weight and mortality. In basic terms, the recent observations suggest that both obesity and unintentional weight loss are indeed associated with poor long-term survival in RA. Although obese patients with RA seem to live longer, obesity is not likely to be biologically protective, but simply is a sign that the individual has not recently lost a substantial amount of weight.