Effectiveness of an intensive weight-loss program for severe OSA in patients undergoing CPAP treatment: a randomized controlled trial
2020; American Academy of Sleep Medicine; Volume: 16; Issue: 4 Linguagem: Inglês
10.5664/jcsm.8252
ISSN1550-9397
AutoresCarla López‐Padrós, Neus Salord, Carolina Pantuzzo Leão Alves, Núria Vilarrasa, Mercè Gasa, Rosa Planas, Monica Montsserrat, María Nuria Virgili, Carmen Rodrı́guez, Sandra Pérez-Ramos, Esther López-Cadena, M. Inmaculata Ramos, Jordi Dorca, Carmen Monasterio,
Tópico(s)Cardiovascular Syncope and Autonomic Disorders
ResumoFree AccessScientific InvestigationsEffectiveness of an intensive weight-loss program for severe OSA in patients undergoing CPAP treatment: a randomized controlled trial Carla López-Padrós, MD, Neus Salord, PhD, Carolina Alves, BND, Núria Vilarrasa, PhD, Merce Gasa, PhD, Rosa Planas, MD, Monica Montsserrat, BND, M. Nuria Virgili, PhD, Carmen Rodríguez, BN, Sandra Pérez-Ramos, BN, Esther López-Cadena, MD, M. Inmaculata Ramos, MD, Jordi Dorca, PhD, Carmen Monasterio, PhD Carla López-Padrós, MD Multidisciplinary Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; , Neus Salord, PhD Multidisciplinary Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; Section of Respiratory Medicine, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Spain; , Carolina Alves, BND Section of Endocrinology, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; , Núria Vilarrasa, PhD Section of Endocrinology, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; Department of Endocrinology and Nutrition Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM-CIBER), Spain; , Merce Gasa, PhD Multidisciplinary Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; Section of Respiratory Medicine, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Spain; , Rosa Planas, MD Department of Rehabilitation, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; , Monica Montsserrat, BND Department of Endocrinology and Nutrition Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; , M. Nuria Virgili, PhD Section of Endocrinology, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; Department of Endocrinology and Nutrition Department, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; Department of Medicine, Universitat de Barcelona, Campus Bellvitge, L'Hospitalet de Llobregat, Spain; , Carmen Rodríguez, BN Multidisciplinary Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; , Sandra Pérez-Ramos, BN Multidisciplinary Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; , Esther López-Cadena, MD Respiratory Medicine Department, Hospital Universitari Sagrat Cor, Barcelona, Spain; , M. Inmaculata Ramos, MD LINDE Healthcare, Spain , Jordi Dorca, PhD Multidisciplinary Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; Section of Respiratory Medicine, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; Department of Medicine, Universitat de Barcelona, Campus Bellvitge, L'Hospitalet de Llobregat, Spain; , Carmen Monasterio, PhD Multidisciplinary Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Spain; Section of Respiratory Medicine, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Spain; Published Online:April 15, 2020https://doi.org/10.5664/jcsm.8252Cited by:13SectionsAbstractPDFSupplemental Material ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations AboutABSTRACTStudy Objectives:To determine whether an intensive weight-loss program (IWLP) is effective for reducing weight, the severity of obstructive sleep apnea (OSA), and metabolic variables in patients with obesity and severe OSA undergoing continuous positive airway pressure treatment.Methods:Forty-two patients were randomized to the control (CG, n = 20) or the intervention group (IG, n = 22), who followed a 12-month IWLP. The primary outcome was a reduction in the apnea-hypopnea index (AHI) as measured at 3 and 12 months by full polysomnography. Metabolic variables, blood pressure, body fat composition by bioimpedance, carotid intima media thickness, and visceral fat by computed tomography were also assessed.Results:Mean age was 49 (6.7) years, body mass index 35 (2.7) kg/m2, and AHI 69 (20) events/h. Weight reduction was higher for the IG than the CG at 3 and 12 months, −10.5 versus −2.3 kg (P < .001), and −8.2 versus −0.1 kg (P < .001), respectively, as was loss of visceral fat at 12 months. AHI decreased more in the IG at 3 months (−23.72 versus −9 events/h) but the difference was not significant at 12 months, though 28% of patients from the IG had an AHI < 30 events/h compared to none in the CG (P = .046). At 12 months, the IG showed a reduction in C-reactive protein (P = .013), glycated hemoglobin (P = .031) and an increase in high density lipoprotein cholesterol (P = .027).Conclusions:An IWLP in patients with obesity and severe OSA is effective for reducing weight and OSA severity. It also results in an improvement in lipid profiles, glycemic control, and inflammatory markers.Clinical Trial Registration:Registry: ClinicalTrials.gov; Title: Effectiveness of an Intensive Weight Loss Program for Obstructive Sleep Apnea Syndrome (OSAS) Treatment; Identifier: NCT02832414; URL: https://clinicaltrials.gov/ct2/show/record/NCT02832414Citation:López-Padrós C, Salord N, Alves C, et al. Effectiveness of an intensive weight-loss program for severe OSA in patients undergoing CPAP treatment: a randomized controlled trial. J Clin Sleep Med. 2020;16(4):503–514.BRIEF SUMMARYCurrent Knowledge/Study Rationale: Few studies have demonstrated a significant improvement in obstructive sleep apnea (OSA) severity through weight-loss programs, and there is still a lack of evidence regarding the effect of these programs on populations of patients with severe OSA.Study Impact: An intensive weight-loss program reduces the severity of OSA in patients with severe OSA undergoing continuous positive airway pressure treatment, results in a reduction in apnea-hypopnea index to below 30 events/h in a significant percentage of patients, and achieves small but significant benefits in patients' metabolic profile. Weight-loss programs should therefore be considered for patients with severe OSA, even if they respond well to continuous positive airway pressure, in order to optimize their global health.INTRODUCTIONObstructive sleep apnea (OSA) is a common disorder affecting 14% of men and 5% of women when defined by an apnea-hypopnea index (AHI) ≥ 5 events/h and symptoms of daytime sleepiness.1,2 Obesity, particularly central adiposity, is one of the main risk factors for sleep apnea.3 Obesity predisposes patients to OSA through multiple mechanisms.4 The prevalence of OSA has increased as a result of a progressive increase in obesity.1,2 The gold standard treatment for OSA is continuous positive airway pressure (CPAP) therapy.5 This therapy is a highly efficacious treatment that prevents main airway collapse, corrects oxyhemoglobin saturation, and reduces the cortical arousals associated with apneic/hypopneic events. When there is good adherence, CPAP improves OSA-related symptoms and quality of life and reduces traffic accidents, high blood pressure, and cardiovascular risk in individuals with severe OSA.6 However, because it is a long-term treatment, low adherence to CPAP can limit its overall effectiveness.7Weight loss is considered to be an adjuvant treatment for OSA.8 However, although most patients with OSA undergoing CPAP treatment are obese, only a few manage to lose weight. In fact, a meta-analysis of randomized controlled studies demonstrated that patients undergoing CPAP treatment experienced a small but significant increase in body mass index (BMI) and weight.9 In many health care settings, such as ours, this failure to lose weight is due to a lack of access to adequate protocols addressing weight reduction.10 A small number of studies have shown that intensive diet programs, accompanied by exercise and especially behavioral counseling, have an effect on OSA severity in different OSA populations.11–19 These studies focused mainly on patients with mild to moderate OSA who were naive to any OSA treatment, and a few also included severe cases. These studies revealed a dose-response association between weight loss and AHI11–13 and greater improvements in patients with severe disease.12,13 Whether or not an intensive weight-loss program (IWLP) provides effective long-term improvements in cases of severe OSA has yet to be demonstrated.The interrelationships between obesity and OSA are complex and bidirectional. Obesity causes metabolic syndrome and multiple epidemiologic and clinical studies suggest an independent association of OSA with the different components of metabolic syndrome, particularly insulin resistance, hypertension, and abnormal lipid metabolism.20 OSA may increase visceral fat dysfunction, which could play a fundamental role in the relationship between obesity and metabolic dysfunction.20 Whether treatment with CPAP alone is able to control metabolic alterations is still under study and a few studies have demonstrated an improvement in oral glucose tolerance and insulin sensitivity.21–23 A number of positive effects on lipid metabolism have also been described.24 A recent study has shown that CPAP, associated with a weight-loss program, increases insulin sensitivity and reduces serum triglyceride levels, but no improvement was observed with CPAP treatment alone,25 which raises the important issue of the usefulness of adding weight-loss programs to CPAP treatment in order to improve the cardiovascular risk factor profile of obese patients with OSA.We hypothesized that patients with obesity and OSA who are already undergoing CPAP treatment are able to achieve weight loss and subsequently a general improvement in OSA, as well as obtaining beneficial effects on metabolic syndrome and subclinical cardiovascular disease. This study therefore aimed to analyze the effect on weight loss, OSA severity, and metabolic variables of a 12-month IWLP with patients with severe OSA undergoing CPAP treatment.METHODSTrial designA randomized controlled parallel-group prospective study was designed. Patients were randomly assigned to a group either undergoing an IWLP or receiving standard lifestyle recommendations over a period of 12 months. Randomization was performed using a computer-generated automated program including block randomization with a block size of 5.At baseline, all variables were measured and the patients in the intervention group began the IWLP, while the patients in the control group continued with their regular medical visits. Sleep studies were repeated at 3 months and at 1 year and all variables were measured again.ParticipantsPatients were recruited from the Sleep Unit at the Bellvitge University Hospital outpatient clinic. Recruitment started in November 2014 and ended in April 2016. The inclusion criteria were as follows: age 25–60 years, class I and II obesity (BMI 30–40 kg/m2), severe OSA (AHI > 30 events/h), and treatment with CPAP for a minimum of 6 months previous to inclusion. Exclusion criteria were: contraindications for physical activity or diet, cognitive impairment, or psychiatric disorders that impeded patients' understanding of the program; severe diseases; major cardiovascular disease; clinical instability within the previous month; prior bariatric surgery; refusal to participate in the study; and participation in another clinical trial. The study protocol was approved by the local ethical committee (PR209/14). All participants provided written informed consent. The clinical trial registration number was NCT02832414.Procedures and measurementsSleep studyAll patients underwent polysomnography (PSG) at baseline, at 3 months, and at 12 months. Patients were instructed to cease CPAP treatment for 3 nights prior to PSG. Apnea was defined as an absence or a 90% decrease in airflow for at least 10 seconds.26 Hypopnea was defined as a reduction in airflow with a minimum duration of 10 seconds, in association with 3% oxygen desaturation or an arousal.26 The AHI was defined as the total number of apnea or hypopnea events/h of sleep. Supine time was defined as the percentage of time spent in supine position in relation to recording time.Other assessmentsSociodemographic data were assessed at baseline. Measurement of visceral fat by abdominal computed tomography was performed at baseline and at 12 months.27 The following assessments were carried out at baseline and at 3 and 12 months: anthropometric variables; body fat composition; general medical history and OSA-related symptoms; self-reported sleepiness assessed by the Epworth Sleepiness Scale28; health-related quality of life measured by the Spanish language version of the Functional Outcomes of Sleep Questionnaire29 and the Spanish language version of the Quebec Sleep Questionnaire30; assessment of well-being by EuroQol31 and the visual analogical well-being scale; measurement of pain by the visual analog scale; subclinical cardiovascular disease measured as carotid intima-media thickness (IMT) by ultrasonography of the supra-aortic vessels; blood pressure; CPAP adherence by the mean hours of usage per night recorded by the time counters; CPAP related side-effects by means of a brief questionnaire; routine laboratory tests including complete blood count, blood coagulation tests, and basic biochemical tests.Intensive weight-loss programPatients randomized to the intervention group followed an IWLP under the supervision of an expert nutritionist who conducted behavioral counseling during all the visits. The program consisted of a very low calorie diet (600–800 kcal) with low-calorie liquid meal replacements during 15 days and a 1,200 kcal diet during the rest of the initial intensive diet phase lasting 12 weeks, followed by a hypocaloric (1,200–1,800 kcal) Mediterranean diet32 for the remaining 36 weeks. Unsupervised physical activity was introduced after 15 days. The full protocol is described in the supplemental material.Control groupThe participants in the control group were given general oral and written information about diet and exercise at baseline. To estimate nutrient intake, patients completed a 24-hour food record at baseline, and again at 3 and 12 months.Statistical analysisThe primary endpoint was a reduction in AHI at 12 months compared to baseline. The null hypothesis was that there would be no differences between the means of the intervention group and the control group. Secondary end points included an improvement in blood pressure levels, lipid profile and glycemic control, a reduction in the risk of subclinical cardiovascular disease, and a reduction in visceral adiposity as well as in other measures of obesity.The main variable was the reduction in participants' final AHI with respect to baseline. Accepting an alpha risk of 0.05 and a power of 80% in a bilateral approach, a final sample of 42 patients was deemed sufficient to detect a difference of 15 points in the AHI between the control and intervention groups (a clinically relevant difference), considering a standard deviation of 15 and a loss of 25%. Balanced groups were estimated.Categorical variables were presented as the number of cases and percentages, and continuous variables as mean and standard deviation or median and interquartile rank. Continuous variables were compared using the t test or the Mann-Whitney U test, as appropriate. Fisher exact test or Pearson χ2 test were applied to assess the relationship between categorical variables. To identify the factors associated with AHI, we estimated a linear mixed-effects model, using the lme4 package33 for R. This method accounts for clustered data within the same participant, using repeated AHI measurements over time. To show the magnitude of the association, we reported regression coefficients corresponding to the fixed effects and their corresponding 95% confidence intervals, and values of P. All model assumptions were assessed graphically and analytically. Full models were built by adding adjusting covariates one at a time, which were finally included in the model if the modified estimated effect > 10%. The adjusting variables considered were treatment groups; sex; variables related to weight and its distribution, such as basal weight, BMI, waist circumference and neck circumference, and weight difference at 3 and 12 months; and supine time at baseline, 3 and 12 months, and variables related to the PSG that could influence on the AHI variation such as percentage of supine time, positional OSA, and sleep efficiency.Analyses were performed with R software 3.4.0.34 The level of statistical significance was set at 5%.RESULTSA total of 42 patients (38 male and 4 female) with a mean age of 49 (6.7) years, a mean baseline BMI of 35 (2.7) kg/m2, and a mean AHI of 69 (20) events/h were randomized to the intervention (n = 22) or the control (n = 20) group. Four patients from the control group left the study, whereas only 1 patient in the intervention group left (Figure 1). Three patients from the intervention group had an AHI below 30 events/h in the baseline PSG of the trial and were therefore not included in the per-protocol analysis. There were no differences in the main characteristics between per-protocol and intention-to-treat analyses; therefore, the data shown are from the per-protocol analysis, for which all data are available. The baseline characteristics of the participants are shown in Table 1. Even when patients were randomized, those in the control group, despite having a similar BMI, had a predominance of central adiposity (higher waist circumference, waist/hip ratio, and fat mass that reached statistical significance). No differences were found regarding comorbidities in the two groups. Hypertension was the most prevalent comorbidity, followed by dyslipidemia.Figure 1: Study flowchart.ITT = intention-to-treat, PP = per-protocol.Download FigureTable 1 Characteristics of the study population at baseline (n = 34).Control (n = 16)Intervention (n = 18)PaAge, years52.0 (45.0; 54.0)49.5 (46.2; 52.8).377bSex, n (%).604c Male15 (93.8)15 (83.3) Female1 (6.3)3 (16.7)Ethnicity Caucasian, n (%)16 (100.0)18 (100.0)Smoking, n (%)3 (18.8)2 (11.1).648cAlcohol, n (%)6 (37.5)5 (27.8).812dWeight, kg106 (8.8)99.5 (10.7).073BMI, kg/m235.4 (2.9)34.5 (2.6).343Neck circumference, cm43.9 (2.4)42.5 (2.5).113Waist circumference, cm118 (8.6)109 (7.4).006Neck circumference / height ratio0.3 (0.02)0.3 (0.01).515Waist circumference / height ratio0.7 (0.06)0.7 (0.05).056Waist circumference / hip circumference ratio1.00 (1.00; 1.10)1.00 (1.00; 1.00).042bFat mass, kg42.9 (6.47)36.7 (8.8).029Fat free mass, kg61.4 (58.6; 67.7)62.8 (60.5; 68.9).449bBody fat, %40.0 (35.8; 44.0)33.0 (32.0; 44.0).074bVisceral fat area L3-L4, cm2291 (91.6)240 (68.9).082Visceral fat area L4-L5, cm2207 (63.3)173 (62.1).136Subcutaneous fat area L3-L4, cm2349 (88.5)320 (105).388Subcutaneous fat area L4-L5, cm2414 (97.2)392 (111).537Hypertension, n (%)6 (37.5)6 (33.3)> .999dDiabetes mellitus, n (%)3 (18.8)0 (0.0).094cDyslipidemia, n (%)4 (25.0)4 (22.2)> .999cStroke, n (%)1 (6.3)0 (0.0).471cIschemic heart disease, n (%)0 (0.0)2 (11.1).487cValues are expressed as mean (standard deviation), median (Q1; Q3), or n (%) where indicated. Significant P < .05 are in bold. aUnless otherwise specified, t test. bMann-Whitney U test. cFisher exact test. dChi-square test. BMI = body mass index.There were no differences between the two treatment groups in respiratory variables (Table 2). CPAP adherence was higher in control group without reaching statistical significance.Table 2 Respiratory variables at baseline (n = 34).Control (n = 16)Intervention (n = 18)PaSleep efficiency, %76.0 (71.0; 82.0)83.5 (74.2; 91.2).157bDeep sleep, %10.9 (8.0)14.8 (10.1).214Superficial sleep, %76.8 (11.5)75 (13.0).669REM sleep, %12.2 (5.81)10.2 (5.2).293Total AHI, events/h69.0 (15.4)69.8 (23.9).904Supine AHI, events/h80.6 (19.9)71.3 (28.7).274Nonsupine AHI, events/h55.4 (25.0)57.7 (31.7).820Supine AHI / nonsupine AHI ratio1.4 (1.02; 1.94)1.2 (0.99; 2.14).259bREM AHI, events/h64.1 (20.0)51.4 (25.0).111Non-REM AHI, events/h69.8 (16.0)71.0 (25.0).863Positional OSAd, n (%)4 (25.0)5 (27.8)> .999Supine time, %48.6 (24.7)53.5 (27.5).593Time with SpO2 < 90, %8.00 (4.0; 15.2)8.5 (6.0; 16.8).717bCPAP adherence, hours5.55 (1.77)4.83 (1.59).237CPAP pressure, cm H2O11 (9.75; 12)10 (9; 12).526bNasal mask / full face mask, n (%)12 (75) / 4 (25)15 (83) / 3 (17).681cEpworth Sleepiness Scale10.1 (4.27)8.17 (4.79).217Values are expressed as the mean (standard deviation), median (Q1; Q3), or n (%) where indicated. at test (unless otherwise specified). bMann-Whitney U test. cFisher exact test. dPositional OSA: AHI > 5 events/h and respiratory events occur at twice the frequency in the supine sleeping position than in nonsupine sleeping position and there is a minimum of 15 minutes in both positions. AHI = apnea-hypopnea index, CPAP = continuous positive airway pressure, OSA = obstructive sleep apnea, REM = rapid eye movement, SpO2 = arterial oxygen saturation.Anthropometric parametersChanges in anthropometric parameters are shown in Table 3. Between baseline and 3 months, patients in the intervention group achieved a total loss of 10.6% with respect to their initial weight. This figure was 8.2% at 12 months. Changes were significant compared to the control group (Figure 2A). BMI, neck circumference, and waist/height ratio showed a greater reduction at 3 months, which was sustained at 12 months in the intervention group. In terms of body composition measured by bioimpedance, the percentage of body fat registered a significant reduction at 3 and 12 months in the intervention group. Visceral obesity measured by abdominal computed tomography was significantly lower in the intervention group than in the control group.Table 3 Changes in anthropometric, respiratory and metabolic variables between baseline and 3 months and baseline and 12 months (n = 34).3 Months12 MonthsControlInterventionPaControlInterventionPaWeight, kg−2.3 (4.3)−10.5 (3.7)< .001−0.1 (4.8)−8.2 (5.9)< .001BMI, kg/m2−0.8 (1.4)−3.65 (1.2)< .001−0.07 (1.5)−2.8 (1.9)< .001Neck circumference, cm−0.4 (1.2)−2.06 (1.3)< .0010.0 (1.6)−2.2 (1.4)< .001Waist / hip ratio0.0 (−0.1; 0.0)0.0 (−0.02; 0.0).717b0.0 (0.0; 0.1)0.0 (0.0; 0.07).173bWaist / height ratio−0.02 (0.03)−0.05 (0.02).001−0.01 (0.03)−0.03 (0.04)< .018Fat mass, kg−2.96 (7.47)−7.4 (5.4).085−1.1 (7.5)−9.96 (10.1).024Fat free mass, kg1.5 (−0.95; 4.4)−1.9 (−2.2; 0.5).167b−0.6 (−0.9; 4.6)−0.7 (−4.9; 3.1).467bBody fat, %−2.0 (−4.0; 0.8)−5.0 (−8.0; −4.0).030b0.0 (−2.0; 1.0)−8.0 (−12.0; −6.0).019bVisceral fat area L3-L4, cm2–––12.9 (49.5)−61.2 (55.7)< .001Visceral fat area L4-L5, cm2–––17.4 (41.9)−42.53 (35.5)< .001Total AHI, events/h−9 (25.2)−23.7 (16.1).056−13.5 (24.8)−19.4 (15.1).414Supine AHI, events/h−15.1 (32.1)−12.0 (41.0).805−9.9 (37.7)−12.5 (38.0).845Non supine AHI, events/h−9.0 (28.6)−21.9 (30.8).213−20.4 (31.8)−18.2 (29.1).830Supine AHI/nonsupine AHI−0.3 (−0.72; 0.01)0.69 (0.33; 2.07).002b0.3 (0.00; 1.03)0.2 (−0.35; 2.48).721bSleep efficiency, %2.1 (10.6)2.2 (12.4).9804.8 (9.6)4.1 (10.3).853Supine time, %−2.3 (28.6)−4.3 (33.7).850−2.2 (28.0)−1.1 (29.7).909REM sleep time, %−1.2 (5.6)5.6 (5.5).0011.5 (5.7)6.3 (6.2).026Deep sleep time, %4.4 (8.9)4.4 (8.6).9876.3 (9.3)5.9 (9.1).910Superficial sleep time, %−2.6 (13.1)−10.1 (13.0).105−7.8 (11.6)−12.5 (13.6).288Time with SpO2 < 90%, %1.0 (−6.3; 3.0)−5.0 (−11.5; −2.0).047−1.0 (−8.0; 6.0)−3.0 (−5.0; 0.8).417bEpworth Sleepiness Scale−2.5 (−4.25; 1)−3 (−5.75; −0.5).7420 (−3; 2.25)1 (−2.75; 4.5).359CPAP adherence0.1 (−0.03; 0.67)−0.1 (−0.97; 0.97).2720.31 (0.03; 1.28)−0.69 (−1.98; 0.21).011Systolic blood pressure, mm Hg0.3 (9.8)−3.78 (22.0).482−5.00 (21.1)−9.35 (21.0).558Diastolic blood pressure, mm Hg0.5 (12.7)−4.78 (11.4).215−1.69 (15.8)−5.88 (12.0).400Glucose, mmol/L0 (−0.4; 0.2)−0.5 (−0.70; −0.02).047b−0.05 (−0.43; 0.4)−0.4 (−0.6; 0.07).360bTriglycerides, mmol/L0.05 (0.7)−0.3 (0.4).143−0.09 (0.9)−0.3 (0.3).396Total cholesterol, mmol/L−0.3 (0.7)−0.6 (0.69).279−0.4 (1.2)−0.2 (0.8).587LDL-C, mmol/L−0.2 (0.7)−0.6 (0.8).177−0.50 (1.35)−0.31 (0.8).633HDL-C, mmol/L−0.07 (0.4)0.05 (0.3).345−0.02 (0.18)0.20 (0.3).027CRP, mg/L0 (−1.0; 0.0)−1.0 (−1.75; 0.0).440b0 (−1.0; 1.0)−1.0 (−2.0; −0.25).013bHbA1c, %−0.10 (−0.23; 0.0)−0.25 (−0.37; −0.10).155b−0.10 (−0.2; 0.1)−0.2 (−0.30; −0.13).031bValues are expressed as the mean (standard deviation) or median (Q1; Q3). Significant P < .05 are in bold. at test (unless otherwise specified). bMann-Whitney U test. AHI = apnea-hypopnea index, BMI = body mass index, CPAP = continuous positive airway pressure, CRP = C-reactive protein, HbA1c = glycated hemoglobin, HDL-C = high density lipoprotein cholesterol, LDL-C = low density lipoprotein cholesterol, OSA = obstructive sleep apnea, REM = rapid eye movement, SpO2 = arterial oxygen saturation.Figure 2: Change in weight and change in AHI.(A) Change in weight over the follow-up period. The mean values are represented by dots. (B) Change in apnea-hypopnea index over the follow-up period. AHI = apnea-hypopnea index.Download FigureAdherence to diet and physical exercise programDuring the first 2 weeks, ketone levels were positive in all patients. During the following 10 weeks, all patients maintained a restriction of 500–700 kcal according to their 24-hour food records. During the past 9 months, only 22% of patients maintained a restriction of 500–700 kcal.At 3 months, 7 patients (43.8%) from the intervention group met the goal of > 150 minutes of physical exercise per week, decreasing to 3 patients (17.6%) at 12 months. However, 33.3% of patients from the control group practiced > 150 minutes of physical exercise per week at 3 months, decreasing to 4 patients (26.7%) at 12 months.Respiratory and sleep parametersAt 3 months, the mean change in AHI was significantly higher in the intervention group. At 12 months, AHI improvement was maintained in the intervention group but there was no significant difference in AHI reduction between groups due to an unexpected improvement in the control group (Table 3 and Figure 2B).Regarding OSA severity, using AHI cutoffs for mild, moderate, and severe OSA, at 12 months, 1 patient in the intervention group had improved by 2 categories and 4 patients had improved by 1. No one in the control group had improved their OSA category at 12 months. As a result, 28% of patients in the treatment group changed from severe OSA to mild-moderate, compared to none in the control group (P = .046, Fisher exact test).A significant improvement was observed in the percentage of rapid eye movement (REM) sleep time in the intervention group compared with the control group at 3 and 12 months. No other differences were found regarding sleep variables.Over the follow-up, the patients in the control group improved CPAP adherence, whereas adherence decreased in the intervention group, reaching statistical significance at 12 months.Association between AHI reduction and weight change categoriesAt 3 months of follow-up, all of the patients in the intervention group showed a weight reduction of at least 5 kg (Figure 3). Moreover, a positive association was observed between AHI reduction and weight loss at that time. Hence, patients with a higher weight decrease were those with a greater AHI reduction.Figure 3: Association between AHI and weight reduction at 3 and 12 months.AHI = apnea-hypopnea index.Download FigureIn contrast, at 12 months of follow-up weight reduction was less pronounced in the intervention group and an improvement in AHI was observed in some patients in the control group, even in cases without weight loss.The correlation between weight change and AHI change was .522 (95% confidence interval .223, .731) from baseline to 3 months and .360 (95% confidence interval .025, .622) from baseline to 12 months.Mixed-effects models estimating change in AHI over timeTo compare the value of AHI at the baseline visit, at 3 months, and at 12 months, we fitted a mixed-effects model adjusted for potential confounders. The change in AHI (outcome variable) adjusted by sex and baseline weight was related to changes in weight and in supine time (predictor variables). Decreasing the time spent in the supine position decreased the AHI (for each decrease of 10% of supine time, AHI is expected to decrease by almost 3 points). Losing weight also decreases the AHI; for every kilogram of weight lost, the AHI is expected to decrease by 1.43 points (Table 4). Figure 4 shows a graphic representation of the change in AHI considering its interaction with the change in weight and the change in time spent in supine position.Table 4 Mixed-effects models estimating change in apnea-hypopnea index over time (n = 34).BCIP(Intercept)88.4766.02 to 110.92< .001Baseline weight0.890.25 to 1.54.009Intervention group2.33−10.45 to 15.11.723Male−25.87−45.25 to −6.48.011Visit 2−27.51−41.99 to −13.04< .001Visit 3−26.57−41.96 to −11.17.001Supine time visit 10.05−0.16 to 0.26.636Supine time visit 20.280.08 to 0.47.008Supine time visit 30.260.04 to 0.49.027Weight change visit 21.430.43 to 2.43.007Weight change visit 30.82−0.04 to 1.67.066Intraclass correlation coefficient = 0.574. CI = confidence interval.Figure 4: 3D surface plot contrasting apnea-hypopnea in
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