The impact of CPAP on cardiovascular biomarkers in minimally symptomatic patients with obstructive sleep apnea: a pilot feasibility randomized crossover trial.
BACKGROUND
Previous, largely uncontrolled studies demonstrated the substantial effects of continuous positive airway pressure ventilation (CPAP) on a variety of physiologic and biochemical markers known to be risk factors for cardiovascular disease in patients with obstructive sleep apnea (OSA). In this pilot crossover study, we assessed (1) the feasibility of using CPAP in a group of minimally symptomatic patients with OSA, assessed through patient compliance and (2) CPAP therapy's effect on biomarkers in these patients.


METHODS
We studied patients with minimal daytime sleepiness who were referred to the University of British Columbia's Hospital Sleep Clinic with suspected OSA and an apnea-hypopnea index (AHI) > 15 events/h. Patients were randomized to either CPAP or no therapy for 4 weeks followed by a washout of 4 weeks, and then a crossover to the other intervention. Fasting morning blood and urine, 24-h blood pressure (BP) measurements, and endothelial function (peak flow-mediated dilation to nitroglycerin-mediated dilation ratio) were assessed before and after each study intervention.


RESULTS
Nine adult male and four female patients were studied. Mean (SD) age was 55 (7) years, mean AHI = 27.9/h, mean Epworth Sleepiness Score = 6.8 (11/13 had a score < 10), and mean BMI = 31.1 kg/m(2). Mean compliance with CPAP therapy was 5.53 h/night. Compared to no therapy, potential improvements were observed with CPAP for urinary microalbumin, norepinephrine, and epinephrine to creatinine ratios (decreased by 3.51 mg/mmol, 1.70 nmol/mmol, and 0.95 nmol/mmol, respectively); 24-h BP (systolic decreased by 3.60 mmHg, diastolic by 0.70 mmHg); homeostasis model for insulin resistance score (decreased by 1.11); and endothelial function (increased by 7.4%). However, none of the above differences was significant (p > 0.10).


CONCLUSIONS
In this pilot study there were potential improvements in a variety of cardiovascular biomarkers with CPAP. CPAP compliance was reasonably good even though patients were not particularly sleepy. Accordingly, larger randomized controlled trials in this area appear feasible and warranted.
Comondore
Vikram R
VR
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Cheema
Rupi
R
Fox
Joel
J
Butt
Arsalan
A
John Mancini
G B
GB
Fleetham
John A
JA
Ryan
C Frank
CF
Chan
Sammy
S
Ayas
Najib T
NT
D000419:Albuminuria / Q000652:urine*; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology; D002395:Catecholamines / Q000652:urine*; D045422:Continuous Positive Airway Pressure; D018592:Cross-Over Studies; D004837:Epinephrine / Q000652:urine; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000652:urine; D010865:Pilot Projects; D012307:Risk Factors; D020181:Sleep Apnea, Obstructive / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy
D015415:Biomarkers; D002395:Catecholamines; D008055:Lipids; D002097:C-Reactive Protein; D009638:Norepinephrine; D004837:Epinephrine
Can Respir J. 2006 Oct;13(7):387-92
17036094
Ann Intern Med. 2007 Feb 6;146(3):157-66
17283346
Circ Res. 2005 Sep 30;97(7):698-706
16123334
Lancet. 2005 Mar 19-25;365(9464):1046-53
15781100
Am J Med. 2004 Jul 15;117(2):118-21
15234648
Circulation. 2002 May 28;105(21):2462-4
12034649
Thorax. 2004 Sep;59(9):777-82
15333855
Lung. 2007 Mar-Apr;185(2):67-72
17393240
J Am Coll Cardiol. 2003 Sep 17;42(6):1037-43
13678927
Sleep. 2007 Nov;30(11):1509-14
18041483
Chest. 2006 Jun;129(6):1459-67
16778262
J Clin Sleep Med. 2007 Jun 15;3(4):409-15
17694731
Am J Cardiol. 2003 Aug 21;92(4B):17K-22K
12948872
Am J Respir Crit Care Med. 2002 Mar 1;165(5):677-82
11874813
Lung. 2008 Jan-Feb;186(1):7-12
18066623
Thorax. 2007 Nov;62(11):969-74
17557769
Circulation. 2003 Mar 4;107(8):1129-34
12615790
N Engl J Med. 1993 Apr 29;328(17):1230-5
8464434
Am J Respir Crit Care Med. 2004 Jan 15;169(2):156-62
14512265
Lung. 1999;177(6):391-400
10541889
Circulation. 2000 Nov 21;102(21):2607-10
11085964
Circulation. 2003 Jan 7;107(1):68-73
12515745
Eur Respir J. 2006 Jun;27(6):1229-35
16455835
Lung. 2008 May-Jun;186(3):151-156
18330639
Arch Intern Med. 2003 Mar 10;163(5):565-71
12622603
Chest. 2007 Sep;132(3):843-51
17573492
Arch Intern Med. 2007 Apr 23;167(8):757-64
17452537