In a recent review published in Nature Reviews Rheumatology, Naveed Sattar and Iain McInnes from the University of Glasgow provided insight on a recent a study published in the journal Arthritis & Rheumatology, that found weight loss is a strong predictor of death in patients with Rheumatoid Arthritis (RA).
However, the authors of the review questioned these results and raised other factors that could explain the association between being overweight or obese and a positive effect on mortality in RA patients.
Recent evidence has shown that in contrast to what is observed in the general population, a low body mass index (BMI) is associated with accelerated mortality in patients with rheumatoid arthritis (RA). However, according to the authors of the review, the obesity paradox in RA (that is, the association of lower BMIs with higher mortality) could largely be the result of residual confounding whereby some other illness, subclinical illness, or incompletely captured aspects of RA severity or systemic inflammation, enhance mortality risk and simultaneously induce weight loss or prevent weight gain.
The authors reflect on the approach used in the study of Baker et al., which included appropriate adjustments for important measured confounders including smoking. According to the authors, in the study titled “Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis”, researchers should have excluded smokers since one can never fully adjust for the effects of smoking (the amount and intensity varies considerably) with simple categorical adjustments.
Nevertheless the authors still believe that the data seemed robust, with a clear ‘dose–response’ relationship between degree of weight loss and risk of death. Whilst one cannot distinguish between intentional and unintentional weight loss from electronic records, the authors mentioned that researchers were correct to point out that unintentional weight loss is probably the predominant reason most patients loose appreciable amounts of weight.
These results, therefore, strongly support the conclusion that the obesity paradox in RA is largely the result of residual confounding, whereby some other illness, subclinical illness, or indeed incompletely captured aspects of RA severity or systemic inflammation, enhance mortality risks and simultaneously lower body weight, the latter probably occurring via either impaired appetite or increased loss of body mass (in particular muscle).
According to the review authors, clinicians and researchers need to become more aware of the potential for residual confounding and reverse causality that can hamper interpretations from observational data linking obesity to outcomes. They suggest the use of serial assessments in research and genetics which should help reach a better understanding of the causal associations in areas of contention and, in turn, improve relevant clinical practice in autoimmune diseases and other related conditions.