Thromb Haemost 2012; 108(04): 701-709
DOI: 10.1160/TH12-04-0231
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Diurnal changes and levels of fibrin generation are not altered by continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA)

A randomised, placebo-controlled crossover study
Bradley J. McEwen*
1   Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
2   Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
,
Craig L. Phillips*
3   Department of Respiratory & Sleep Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
4   NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia
,
Marie-Christine Morel-Kopp
1   Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
2   Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
,
Brendon J. Yee
4   NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia
5   Department of Respiratory & Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
,
David R. Sullivan
6   Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
,
Christopher M. Ward
1   Northern Blood Research Centre, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia
2   Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
,
Geoffrey H. Tofler
7   Department of Cardiology, Royal North Shore Hospital, New South Wales, Australia
,
Ronald R. Grunstein
4   NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia
5   Department of Respiratory & Sleep Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
› Author Affiliations
Financial support: This research was supported through the National Health and Medical Research Project Grant 301936 (RRG) and Fellowship 571179 (CLP) and 1022730 (RRG); NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS) (CLP). BJM is the recipient of a North Shore Heart Research Foundation Scholarship.
Further Information

Publication History

Received: 10 April 2012

Accepted after major revision: 28 July 2012

Publication Date:
29 November 2017 (online)

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Summary

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular disease (CVD) risk. In the general population, CVD events peak at 9:00–10:00 AM, associated with diurnal changes in thrombotic potential. However in OSA, these CVD events occur frequently at night. Measuring thrombotic potential across the sleep-wake cycle may provide insight into the temporal association of OSA with CVD. This study aimed to determine diurnal changes in fibrin generation in OSA and whether treatment of OSA with continuous positive airway pressure (CPAP) alters fibrin generation across the sleep-wake cycle. In a randomised placebo-controlled crossover trial, patients with OSA were assigned to two months each of therapeutic CPAP and placebo. After each treatment period, fibrin generation was determined by overall haemostatic potential assay at seven time points over 24 hours (h). Twenty-eight patients (25 men, 3 women) with severe OSA (Apnoea Hypopnoea Index = 37.9 ± 23.9/h, Oxygen Desaturation Index 31.3 ± 22.4/h) completed the study. All parameters, except lag time to fibrin generation, showed significant diurnal changes, both on CPAP and placebo. Compared to 9:00 AM, fibrin generation parameters were significantly lower at midnight and 3:00 AM for overall coagulation potential (OCP), overall haemostasis potential (OHP), maximum optical density, and maximum slope (all p≤0.001). CPAP produced no change in fibrin generation parameters compared to placebo. In severe OSA patients, fibrin generation peaked at 6:00 AM and 9:00 AM rather than during the sleep period (midnight and 3:00 AM). These findings suggest a prothrombotic shift in the morning similar to individuals without OSA. There was no difference between CPAP and placebo on fibrin generation.

* BJM and CLP are equal first authors.