weight gain and cpap

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The complex relationship betweenweight and sleep apnoea

Sanjay R Patel

Obesity has long been recognised as the

most important reversible risk factor forobstructive sleep apnoea (OSA). Analysesfrom the Wisconsin Sleep Cohort Studysuggest that 41% of adult OSA cases,including 58% of moderate-to-severecases, are attributable to overweight orobesity.1 As such, weight loss has longbeen recommended as an ancillary treat-ment for OSA. Longitudinal analysesfrom the Sleep Heart Health Studysupport the notion that weight loss isassociated with improvements in OSAseverity.2 However, the benecial impact

of weight loss was much less than theadverse effect of the same amount of weight gain in that study suggesting thatthe relationship between obesity and OSAis more complex than can be explained byan acute (and reversible) unidirectionalcausal model.

Given evidence that short sleep dura-tions and poor quality sleep predict anincreased rate of weight gain,3 4 manyhave postulated that OSA may itself predis-pose to obesity. Retrospective data indicatethat those with recently diagnosed OSAare more likely to have had recent weight

gain.5 These ndings have been used tosupport the contention that OSA causesweight gain but of course, this may simplyreect the impact of weight gain on OSArisk. An association between OSA and ele-vated leptin levels, which fall with CPAPtherapy, suggests that an effect of OSA onweight gain may be mediated by leptinresistance whereby improvements in leptinresistance with OS A treatment wouldproduce weight loss.6 Uncontrolled studieshave reported that initiation of CPAPtherapy is associated with induction of

mild weight loss.

7

However, given thatmost patients are educated on the associ-ation between obesity and OSA at the timeof CPAP prescription, whether these obser-vations were due to CPAP itself or due toconcomitant weight loss attempts by thepatient was never clear. Nevertheless,many clinicians have continued to counsel

their patients that use of CPAP might help

them in losing weight.More recently, analyses from the Apnea

Positive Pressure Long-term Ef cacy Study(APPLES) have lain to rest the myth thatCPAP causes weight loss. In that 6-monthtrial, patients randomised to CPAP gainedweight, whereas those randomised tosham lost weight (presumably due to con-comitant weight loss attempts). The dif-ference between groups (∼1.0 kg) wassmall but statistically signicant.8

Furthermore, a dose–response relationshipwas identied, whereby increased CPAP

adherence was associated with greaterweight gain. In this issue of Thorax,Drager et al9 have now conrmed the

APPLES ndings by conducting ameta-analysis including 25 well-designedrandomised controlled trials (RCTs) enrol-ling over 3000 patients with OSA. Acrossstudies ranging from 1 to 48 months induration, they report that CPAP is asso-ciated with a 0.5 kg weight gain comparedwith control therapy. The authors are tobe congratulated in making use of existingdata from a large number of prior RCTs.

Almost every OSA trial measures weight

at baseline and follow-up, so the datawere readily available even if not previ-ously reported. Given that weight was nota key outcome in any of these trials, thelikelihood of publication or other selec-tion biases in the identication of data forthis meta-analysis is low. Although themeta-regression analyses did not revealany sources of heterogeneity in theweight-promoting effects of CPAP, theseanalyses were hampered by the substantialsimilarity in the populations recruitedacross trials (middle-aged, predominantly

men with severe OSA). Thus, furtherresearch is needed to test for effect modi-cation in important subpopulations.Nevertheless, the ndings stronglyconrm that CPAP therapy for OSA pro-duces a small increase in weight and den-itely does not lead to weight loss.

The cause of this weight gain is not yetclear. The reduction in leptin levels asso-ciated with CPAP therapy may result inincreased hunger if the degree of leptinresistance does not change. Anotherexplanation is that CPAP leads to reducedenergy expenditure during sleep,10 as

work of breathing is reduced due both to

a patent upper airway as well as lungvolumes rising to a more ef cient pointon the pressure–volume curve. Removalof the anorectic effects of hypoxia alsomay play an important role.11

Where the additional weight fromCPAP goes is also not yet known. Anumber of trials have demonstrated nosubstantial impact of CPAP on visceral fat

volume,12 although the imaging methodsused may not be sensitive enough toexclude the small magnitude of weightgain observed. Improvements in growthhormone and insulin-like growth factor1 signalling with CPAP might result inincreased muscle mass.13 Further studiesare clearly needed to determine whetherCPAP-induced weight gain representsincreases in fat, lean body or watercompartments.

In understanding the impact of CPAP, itis important to note that increases in

weight are also observed in overweightchildren with OSA following adenotonsil-lectomy,14 suggesting that weight gain isan effect of eliminating OSA rather thanan effect specic to CPAP. Closer evalu-ation of the effects of other OSA therapiessuch as oral appliances would be helpfulin establishing that the effect is not CPAPspecic. Just as with CPAP, these dataalmost certainly already exist from priorRCTs and are ripe for meta-analysis.

Some readers may wonder if treatmentrecommendations for OSA should bealtered in light of this identied adverse

effect of CPAP therapy. The impact of 0.5 kg weight gain on health outcomes isfairly minimal and so should not changedecision making regarding the use of CPAP in symptomatic OSA. However, itdoes give one pause regarding the use of CPAP in asymptomatic OSA where a car-diovascular benet of CPAP has yet to bedenitively established and makes moreurgent the need for RCTs adequatelypowered to assess meaningful outcomes inthis population.

These ndings also highlight the need

for the regular use of weight loss therapiesin conjunction with CPAP in all over-weight and obese patients with OSA.

Although CPAP does not facilitate weightloss, it does not make weight loss strat-egies less effective either. The amount of weight loss achieved is no different inpatients with OSA randomised to CPAPplus weight loss compared with weightloss alone.15 16 In one small trial, theweight loss achieved with a dietary inter-vention was correlated to level of CPAPadherence suggesting that similar traits(eg, level of self-ef cacy) predict the

effectiveness of both interventions.17

Correspondence to Dr Sanjay R Patel, Division of Sleep and Circadian Disorders, Brigham and Women’sHospital, Harvard Medical School, 221 LongwoodAvenue, Room 225-C, Boston, MA 02115, USA;

[email protected]

Patel SR. Thorax March 2015 Vol 70 No 3 205

Editorial

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Dietary intervention trials have demon-strated an improvement in both OSAseverity and OSA-related symptoms withweight loss.18 19 However, some haveargued that because weight regain iscommon with such lifestyle interventions,there may be little long-term benet onOSA. In fact, several studies have nowestablished that despite some weight

regain, the improvements in OSA severityare durable.20 2 1 Furthermore, a recentRCT demonstrated greater benet i n awide range of cardiovascular risk factorsobtained by combining CPAP with aggres-sive behavioural weight loss than CPAPalone.16 Thus, there is fairly strong evi-dence that intensive behavioural weightloss interventions are benecial in over-weight/obese patients with OSA.Implementation research is now sorelyneeded to determine how best to incorp-orate these lifestyle interventions into

routine OSA care.Further investigation into the role of pharmacological and surgical weight losstreatments in OSA management is anotherresearch priority. Although a recent trialfound no additional benet of gastricbanding surgery over behavioural weightloss in OSA,22 more aggressive bariatricoptions such as gastric bypass or sleevegastrectomy are clearly more effective atweight loss than gastric banding and prob-ably more effective at treating OSA aswell.23 24 No RCTs have yet evaluated theef cacy of these procedures on OSA.

Despite the limitations in currentknowledge, it is clear that clinicians needto pay more than lip service to weight losscounselling. Although practice guidelineson OSA treatment uniformly recommendweight loss be encouraged,25–27 cliniciansneed to do more than just encourage. Theevidence base for intensive lifestyle inter-ventions combining diet, activity andbehavioural support in producing long-term weight loss and improved health out-comes is strong,28 but the tools are cur-rently unfamiliar to most who treat OSA.

Just as respiratory physicians treatingCOPD need to be adept with evidence-based methods for smoking cessation,those treating sleep apnoea need to betrained in best practices for achievingweight loss.

Competing interests None.

Provenance and peer review Commissioned;internally peer reviewed.

To cite Patel SR. Thorax 2015;70:205–206.

Published Online First 8 December 2014

▸ http://dx.doi.org/10.1136/thoraxjnl-2014-205361

Thorax 2015;70:205–206.doi:10.1136/thoraxjnl-2014-206484

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19 Tuomilehto HP, Seppa JM, Partinen MM, et al .Lifestyle intervention with weight reduction: rst-linetreatment in mild obstructive sleep apnea. Am JRespir Crit Care Med 2009;179:320–7.

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and sleep apnoeaThe complex relationship between weight

Sanjay R Patel

doi: 10.1136/thoraxjnl-2014-2064842015 70: 205-206 originally published online December 8, 2014Thorax

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