Reply

To the Editor: The important study by Baker et al on weight and mortality risk in rheumatoid arthritis (RA), reported in Arthritis & Rheumatology (1), raised a lot of interest as well as numerous queries and hypotheses. We would like to summarize the issue the study addresses and provide some comments on how to interpret what the authors refer to as the paradox. It has been estimated that in the general population, for every 4 kg/m increase in body mass index (BMI) there is a 26% increase in risk of ischemic heart disease (2), and ischemic heart disease is the most prevalent cause of death in the Western world. In addition, obesity represents a key risk factor for development of deep venous thrombosis (3), which is in turn a key risk factor for pulmonary embolism (hazard ratio 2.1), and data from the Centers for Disease Control and Prevention clearly show that sudden death is the first symptom in ;25% of people with pulmonary embolism. It has been reported that even RA represents a risk factor for deep venous thrombosis and pulmonary embolism (4). These are a few examples (among several others) of why obesity should be considered a risk factor for death in RA. In the study by Baker et al, the enrolled RA cohort had a low disability index (mean score of 0.93 on the Health Assessment Questionnaire [5]) and low C-reactive protein (CRP) levels (median 8 mg/liter), but a 28-joint Disease Activity Score (6) of 4.06, indicating moderate disease activity; the proportion of patients who were obese (BMI . 30 kg/m) at baseline was 34%, and the proportion with a peak BMI of . 30 kg/m during followup was 58%. When RA patients have a low amount of disability and low CRP concentrations the disease should not be severe, and thus risk of death should be low. However, this cohort had a high prevalence of cardiovascular disease (38%), diabetes (26%), and hypertension (70%). How do we interpret these results? The most frequent cause of death in this RA cohort was indeed cardiovascular disease in current smokers, as opposed to other comorbidities (including malignancies). Why should we consider a weight loss of . 1 kg/m as a risk factor for death and not consider the undulating behavior of body weight as the real cause, given the substantial change between baseline and peak BMI values among the patients? It has long been known that decreasing or increasing body weight is associated with excess mortality, especially when the weight loss is “unintentional” (7). Moreover, we do not have information on the final BMI category reached by the patients in Baker and colleagues’ study, or on BMI at the time of RA diagnosis. To rule out the risk related to unintentional change in body weight, it would be important to know whether and how much the patients who were initially in the obese category changed BMI categories more than once during the followup period and how much this change was related to their RA disease activity. Is it possible to completely rule out changes in disease activity in patients with unintentional weight loss of . 1 kg/m as a possible cause of excess mortality, since it is well known that intentional attempts at weight loss reduce the likelihood of cardiovascular events (7)? Moreover, a stably paced reduction in disease activity decreases cardiovascular risk in RA patients (8). Given that obesity represents a general risk factor for increased systemic inflammation and disease activity in RA (9), such data on intentional and unintentional weight loss could provide insights into how to interpret a very complex paradox.