Continuous Positive Airway Pressure Improves Vascular Function In Obstructive Sleep Apnea Hypopnea Syndrome: A Randomized Controlled Trial

Melanie D Cross ^1*, Nicholas L Mills ¹, Mohammed Al-abri ¹, Renata L Riha ², Marjorie Vennelle ¹, Tom w Mckay ³, David E Newby ¹ and Neil Douglas ⁴

¹ University Of Edinburgh, United Kingdom
² The Royal Infirmary Edinburgh, United Kingdom
³ University of Edinburgh, United Kingdom
⁴ Royal Infirmary, United Kingdom

^* To whom correspondence should be addressed. E-mail: melanie.cross{at}ed.ac.uk.

Accepted 2 December 2007

Abstract

Background The obstructive sleep apnea/hypopnea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy.

Methods and Results We compared vascular function in two groups of patients with OSAHS: 27 with more than twenty 4% desaturations/hr (desaturator group) and 19 with no 4% and less than five 3% desaturations/hr (non-desaturator group). In a randomized double-blind placebo controlled crossover trial, the effect of 6-weeks CPAP therapy on vascular function was determined in the desaturator group. In all studies, vascular function was assessed invasively by forearm venous occlusion plethysmography during intra-arterial infusion of endothelium-dependent (acetylcholine, 5-20 µg/min, and substance P, 2-8 pmol/min) and independent (sodium nitroprusside, 2-8 µg/min) vasodilators. Compared to the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (P0.007 for all). The apnea/hypopnea index and desaturation frequency were inversely related to peak vasodilatation with acetylcholine (r=-0.44, P=0.002 and r=-0.43, P=0.003) and sodium nitroprusside (r=-0.42, P=0.009 and r=-0.37, P=0.02). In comparison to placebo, CPAP therapy improved forearm blood flow to all vasodilators (P0.01).

Conclusions Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial-dependent and endothelial-independent vasodilatation that is proportional to hypoxemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.