Is there a bidirectional relationship between obesity and sleep-disordered breathing?

The association between obstructive sleep apnea and obesity is very strong. Approximately 70% of individuals who have OSA are obese,1 and conversely 50% of obese individuals have OSA.2 Furthermore, weight increase results in greater OSA severity and weight loss can lead to an improvement or resolution of OSA.3 Interestingly, the correlation between weight change and OSA severity may be stronger in men than in women.3 Thus, although there is considerable evidence that changes in weight impact OSA severity, it is unclear whether there is reverse causality such that OSA affects weight. One possible means of addressing this issue is to determine if treatment of OSA results in weight loss. In this issue of the Journal, Redenius and colleagues performed a retrospective chart review of OSA patients compliant with continuous positive airway pressure (CPAP) in comparison to a control group of untreated or inadequately treated OSA patients.4 After an approximately 1 year follow-up, the body mass index (BMI) was not different between the treated and control patients. Moreover, a gender stratified analysis suggests that women who were treated with CPAP actually gained weight. Although these results might be considered surprising, anecdotal observations of clinic patients also find that most obese OSA patients on CPAP do not experience marked weight reduction after initiation of therapy. Limited data in patients undergoing tracheostomy to treat OSA support this conclusion as well.5 Do the results of Redenius et al therefore provide any insight into whether OSA promotes weight gain? Unfortunately, there are several potential shortcomings in this report that must be considered in answering this question. First, small numbers of patients in unequal groups may predispose to Type II error, resulting in erroneous acceptance of the hypothesis that CPAP therapy can result in weight gain. Second, the use of medications, presence of physical and psychiatric comorbidities and heterogeneous dietary habits as well as changes in these variables over a course of a year could have further confounded the results. Third, sleep duration was an important confounder that was not considered. We know that short sleep duration is associated with weight gain and incident obesity in women.6 In this study by Redenius et al, it is interesting that it is women again – and not men – with treated OSA who experienced weight gain. Was their sleep quantity paradoxically reduced following CPAP therapy? This is unclear. Finally, the authors do not provide any indicator of the effectiveness of the treatment, such as normalization of the apnea-hypopnea index with therapy. The proportion of “treated” patients receiving optimal treatment, is thus, unknown. It is possible that even some “compliant” OSA patients in this study were not optimally treated. In contrast to the results of this study, some prior investigations have suggested that CPAP treatment may actually lead to weight loss. One study of 46 obese or overweight patients with OSA reported weight loss in some patients with good adherence to CPAP therapy (albeit by self-report).7 Another study showed a decrease in visceral and subcutaneous fat accumulation in OSA patients after 6 months of CPAP therapy.8 However, weight loss was seen in only 6 of the 13 patients whereas serum leptin levels decreased in all 13. Thus, considering the results of this current study and previous reports, it is not clear whether CPAP therapy will result in weight changes in a particular patient, and if serum leptin plays a role in this. It is possible that CPAP use may improve leptin resistance in patients with OSA and obesity, and hence, they may lose weight despite a decrease in leptin levels. However, if there is a disproportionate drop in leptin levels, the effect may be either no change, or increase in BMI. The results of this study suggest the latter. The results of Redenius et al therefore do not provide definitive data to determine whether OSA affects weight. Nevertheless, the paper deserves merit for the provocative and counter-intuitive results. Additionally, as the authors conclude, treating physicians should not offer weight loss as an additional benefit of CPAP treatment of OSA, and other strategies need to be implemented to achieve this goal. Another approach to assess whether OSA is a risk factor for weight gain would be to longitudinally track weight in a cohorts of individuals with and without OSA and determine their weight trajectories over time. In one small study using recall of self-reported weight, patients with newly diagnosed OSA had a 7.4 kg weight gain over 1 year in comparison to a control group without OSA.9 Although suggestive, considering the number of potential confounders (such as adherence traits, gender influences, physical activity levels, and dietary patterns) a large prospective cohort study with sufficient power and detailed information regarding such confounders will be needed to determine whether OSA is a risk factor for obesity. One such analysis is currently being performed in the Sleep Heart Health Study.