Cardio-Metabolic Health Effects of CPAP Treatment for Sleep Apnoea during Weight Loss: Arandomised Controlled Pilot Trial
Authors List
Camilla M Hoyos1,5, Elizabeth A Cayanan1,4, Brendon J Yee1,3,4, Freya Grove1, Svetlana Postnova1,5, Nathaniel S Marshall1,4, Tania Markovic3,4, Stephen M Twigg3,4, Ronald R Grunstein1,3 and Craig L Phillips1,2.
1 CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research; 2 Faculty of Medicine and Human Health Sciences, Macquarie University; 3 Royal Prince Alfred Hospital; 4 Faculty of Medicine, University
of Sydney; 5 Faculty of Science, University of Sydney
Introduction/Rationale
Obesity is both the primary risk factor for Obstructive Sleep Apnoea (OSA) and a key driver of cardio-metabolic disease. Despite this, limited evidence also suggests that OSA may independently increase the risk for cardiometabolic disease and obesity. To test this ‘reverse causality’ pathway, this study assessed whether adjunctive treatment of OSA with CPAP would enhance metabolic health improvements and weight loss in patients with obesity and OSA undergoing weight loss.
Methods
This pilot randomised trial enrolled patients with obesity (BMI≥27kg.m-2), prediabetes and co-morbid moderate-severe hypoxemic OSA (AHI≥20/hr and ODI≥10/hr). Patients were randomised to receive CPAP therapy with a weight loss (WL) programme or a weight loss programme alone. The programme comprised a 2-month Very Low Energy Diet (500cal/day energy deficit) using meal replacements, combined with a minimum 250 minutes of exercise per week. After 2-months, patients were gradually re-introduced to normal food.
Cardio-metabolic health outcomes assessed at baseline and 3-months included glucose tolerance (oral glucose tolerance test), abdominal fat (Dual Energy X-ray Absorptiometry), Insulin Sensitivity (minimal modelling), Office and 24-hour BP. OSA severity was assessed at baseline and at 3 months by polysomnography. The trial was registered on the Australian and New Zealand Clinical Trials registry (ANZCTRN 12617000823370) at ANZCTR.org.au.
Results
17 of the intended 30 patient target completed the follow-up assessments before the study was stopped due to the covid pandemic. 8 were randomised to CPAP+WL and 9 to WL alone. Mean CPAP compliance was 5.29 hrs/night. The weight loss program was successful (mean weight loss ~12 kg in both groups) and reduced OSA severity by ~45%. There were no between group differences for any of the assessed outcomes. Despite this, most outcomes
improved with weight loss including insulin sensitivity (.000965 units, p=.008), office SBP (- 8.7 mmHg, p=.006) Office DBP (-5.9 mmHg, p=.001), Wake DBP (-4.3mmHg, p=.03), sleep SBP (-16.2 mmHg, p=.0003), Sleep DBP (-9.8 mmHg, p=0.02), and subjective sleepiness (Epworth Sleepiness Score -3.2, p=.0003). Two-hour glucose levels (OGTT) did not improve with weight loss (p=0.33), but the glucose area under the curve (AUC) was reduced (-230 units, p=.009). In addition, total estimated fat mass was reduced by ~-7.6kg (p<.0001) and visceral abdominal fat by ~-310cm3 (p<.0001).
Conclusions
We did not establish any cardio-metabolic benefit from adjunctive CPAP therapy during weight loss although the low sample size likely reduced the power to detect any true benefit. In contrast, weight loss appears to have a robust positive effect on cardiometabolic health with and without CPAP therapy. The magnitude of improvements far exceeded those that have occurred in trials assessing the impact of CPAP alone and suggest that weight loss should be the primary focus of treatment for patients with OSA and obesity.
Funding: Diabetes Australia and Sydney Medical School Foundation, University of Sydney.
Camilla M Hoyos1,5, Elizabeth A Cayanan1,4, Brendon J Yee1,3,4, Freya Grove1, Svetlana Postnova1,5, Nathaniel S Marshall1,4, Tania Markovic3,4, Stephen M Twigg3,4, Ronald R Grunstein1,3 and Craig L Phillips1,2.
1 CIRUS Centre for Sleep and Chronobiology, Woolcock Institute of Medical Research; 2 Faculty of Medicine and Human Health Sciences, Macquarie University; 3 Royal Prince Alfred Hospital; 4 Faculty of Medicine, University
of Sydney; 5 Faculty of Science, University of Sydney
Introduction/Rationale
Obesity is both the primary risk factor for Obstructive Sleep Apnoea (OSA) and a key driver of cardio-metabolic disease. Despite this, limited evidence also suggests that OSA may independently increase the risk for cardiometabolic disease and obesity. To test this ‘reverse causality’ pathway, this study assessed whether adjunctive treatment of OSA with CPAP would enhance metabolic health improvements and weight loss in patients with obesity and OSA undergoing weight loss.
Methods
This pilot randomised trial enrolled patients with obesity (BMI≥27kg.m-2), prediabetes and co-morbid moderate-severe hypoxemic OSA (AHI≥20/hr and ODI≥10/hr). Patients were randomised to receive CPAP therapy with a weight loss (WL) programme or a weight loss programme alone. The programme comprised a 2-month Very Low Energy Diet (500cal/day energy deficit) using meal replacements, combined with a minimum 250 minutes of exercise per week. After 2-months, patients were gradually re-introduced to normal food.
Cardio-metabolic health outcomes assessed at baseline and 3-months included glucose tolerance (oral glucose tolerance test), abdominal fat (Dual Energy X-ray Absorptiometry), Insulin Sensitivity (minimal modelling), Office and 24-hour BP. OSA severity was assessed at baseline and at 3 months by polysomnography. The trial was registered on the Australian and New Zealand Clinical Trials registry (ANZCTRN 12617000823370) at ANZCTR.org.au.
Results
17 of the intended 30 patient target completed the follow-up assessments before the study was stopped due to the covid pandemic. 8 were randomised to CPAP+WL and 9 to WL alone. Mean CPAP compliance was 5.29 hrs/night. The weight loss program was successful (mean weight loss ~12 kg in both groups) and reduced OSA severity by ~45%. There were no between group differences for any of the assessed outcomes. Despite this, most outcomes
improved with weight loss including insulin sensitivity (.000965 units, p=.008), office SBP (- 8.7 mmHg, p=.006) Office DBP (-5.9 mmHg, p=.001), Wake DBP (-4.3mmHg, p=.03), sleep SBP (-16.2 mmHg, p=.0003), Sleep DBP (-9.8 mmHg, p=0.02), and subjective sleepiness (Epworth Sleepiness Score -3.2, p=.0003). Two-hour glucose levels (OGTT) did not improve with weight loss (p=0.33), but the glucose area under the curve (AUC) was reduced (-230 units, p=.009). In addition, total estimated fat mass was reduced by ~-7.6kg (p<.0001) and visceral abdominal fat by ~-310cm3 (p<.0001).
Conclusions
We did not establish any cardio-metabolic benefit from adjunctive CPAP therapy during weight loss although the low sample size likely reduced the power to detect any true benefit. In contrast, weight loss appears to have a robust positive effect on cardiometabolic health with and without CPAP therapy. The magnitude of improvements far exceeded those that have occurred in trials assessing the impact of CPAP alone and suggest that weight loss should be the primary focus of treatment for patients with OSA and obesity.
Funding: Diabetes Australia and Sydney Medical School Foundation, University of Sydney.
