Effects of continuous positive airway pressure on coagulability in obstructive sleep apnoea: a randomised, placebo-controlled crossover study
- Craig L Phillips1,2,
- Bradley J McEwen3,4,
- Marie-Christine Morel-Kopp3,4,
- Brendon J Yee2,5,
- David R Sullivan6,
- Christopher M Ward3,4,
- Geoffrey H Tofler7,
- Ronald R Grunstein2,5
- 1Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
- 2NHMRC Centre for Sleep Health, Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia
- 3Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia
- 4Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
- 5Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
- 6Department of Clinical Biochemistry, Royal Prince Alfred Hospital, St Leonards, New South Wales, Australia
- 7Department of Cardiology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
- Correspondence to Dr Craig L Phillips, Woolcock Institute of Medical Research, PO Box M77, Missenden Road, NSW 2050, Australia;
Contributors Professor Grunstein, Dr Phillips, Dr Yee and Dr Sullivan conceived the original experimental design from which these data have arisen. Professor Grunstein and Dr Phillips jointly obtained research funding from the National Health and Medical Research Council of Australia to conduct this 3-year trial. Professor Tofler, Mr McEwen (PhD candidate), Dr Morel-Kopp, Associate Professor Ward and Dr Phillips were responsible for conceiving which coagulation markers to examine from this study and Mr McEwen and Dr Morel-Kopp performed the assays. Dr Phillips performed all statistical analyses and wrote the original manuscript draft with Mr McEwen. All authors made significant contributions to the interpretation of data and revision of the manuscript for important intellectual content prior to submission.
- Received 28 July 2011
- Accepted 15 January 2012
- Published Online First 14 February 2012
Introduction Obstructive sleep apnoea (OSA) is associated with increased cardiovascular risk, however the mechanisms are not well established.
Objectives This study aimed to determine whether treatment of OSA with nasal continuous positive airway pressure (CPAP) would favourably alter coagulability across the sleep–wake cycle.
Methods In a randomised crossover trial, 28 patients received therapeutic or placebo CPAP, each for 2 months with a 1 month washout between treatments. After each treatment period, a 24 h coagulation study was conducted in the laboratory. Plasminogen activator inhibitor-1 (PAI-1), D-dimer, fibrinogen, von Willebrand Factor (vWF), factor VIII (FVIII), factor VII (FVII) and factor V (FV) were determined at seven time points over the day and night.
Results At baseline, patients had severe OSA (Apnoea Hypopnoea Index 37.9±23.9 events/h). Treatment of OSA with CPAP compared with placebo resulted in lower 24 h levels of vWF (−3.9%, p=0.013), FVIII (−6.2%, p=0.007) and FV (−4.2%, p<0.001). The greatest difference occurred during the nocturnal and early morning periods. In contrast, fibrinogen, D-dimer, FVII and PAI-1 did not differ between treatments, however all markers displayed diurnal variability independent of treatment.
Conclusions In this randomised, placebo-controlled crossover trial, treatment of OSA with CPAP reduced the early morning level of vWF, and nocturnal levels of FVIII and FV. These findings suggest that CPAP may reduce cardiovascular risk in OSA, in part through reducing risk of thrombosis.
- Obstructive sleep apnoea
- continuous positive airway pressure
- diurnal rhythm
- clinical epidemiology
- oxidative stress
- sleep apnoea
- complementary medicine
- oxidative stress
- not applicable
- assisted ventilation
- non invasive ventilation
- pulmonary embolism
CLP, BJM are equal first authors.
Funding This research was supported through the National Health and Medical Research Project Grant 301936 (RRG) and Fellowship 571179 (CLP) and 1022730 (RRG). BJM received a scholarship through North Shore Heart Research Foundation.
Competing interests None to declare.
Ethics approval Ethics approval was provided by Sydney South West Area Health Service HREC.
Provenance and peer review Not commissioned; externally peer reviewed.