Cross M D, Mills N L, Al-Abri M, Riha R, Vennelle M, Mackay T W, Newby D E, Douglas N J
Department of Sleep Medicine, The University of Edinburgh, Chancellor's Building, Edinburgh EH16 4SB, UK.
Thorax. 2008 Jul;63(7):578-83. doi: 10.1136/thx.2007.081877. Epub 2008 Apr 4.
The obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is associated with hypertension and increased cardiovascular risk, particularly when accompanied by marked nocturnal hypoxaemia. The mechanisms of these associations are unclear. We hypothesised that OSAHS combined with severe nocturnal hypoxaemia causes impaired vascular function that can be reversed by continuous positive airways pressure (CPAP) therapy.
We compared vascular function in two groups of patients with OSAHS: 27 with more than 20 4% desaturations/h (desaturator group) and 19 with no 4% and less than five 3% desaturations/h (non-desaturator group). In a randomised, double blind, placebo controlled, crossover trial, the effect of 6 weeks of 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 microg/min and substance P 2-8 pmol/min) and independent (sodium nitroprusside 2-8 microg/min) vasodilators.
Compared with the non-desaturator group, patients with OSAHS and desaturations had reduced vasodilatation to all agonists (p = 0.007 for all). The apnoea/hypopnoea 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 with placebo, CPAP therapy improved forearm blood flow to all vasodilators (p = 0.01).
Patients with OSAHS and frequent nocturnal desaturations have impaired endothelial dependent and endothelial independent vasodilatation that is proportional to hypoxaemia and is improved by CPAP therapy. Impaired vascular function establishes an underlying mechanism for the adverse cardiovascular consequences of OSAHS.
阻塞性睡眠呼吸暂停/低通气综合征（OSAHS）与高血压及心血管疾病风险增加相关，尤其是伴有明显夜间低氧血症时。这些关联的机制尚不清楚。我们推测，OSAHS合并严重夜间低氧血症会导致血管功能受损，而持续气道正压通气（CPAP）治疗可使其逆转。
我们比较了两组OSAHS患者的血管功能：27例每小时血氧饱和度下降超过20次且降幅达4%的患者（低氧组）和19例每小时血氧饱和度下降未达4%且降幅小于5次且降幅达3%的患者（非低氧组）。在一项随机、双盲、安慰剂对照的交叉试验中，测定了低氧组患者接受6周CPAP治疗对血管功能的影响。在所有研究中，通过前臂静脉阻塞体积描记法，在动脉内输注内皮依赖性血管舒张剂（乙酰胆碱5 - 20微克/分钟和P物质2 - 8皮摩尔/分钟）和非内皮依赖性血管舒张剂（硝普钠2 - 8微克/分钟）期间，有创评估血管功能。
与非低氧组相比，伴有血氧饱和度下降的OSAHS患者对所有激动剂的血管舒张反应均降低（所有p值均为0.007）。呼吸暂停/低通气指数和血氧饱和度下降频率与乙酰胆碱（r = -0.44，p = 0.002；r = -0.43，p = 0.003）及硝普钠（r = -0.42，p = 0.009；r = -0.37，p = 0.02）诱导的最大血管舒张呈负相关。与安慰剂相比，CPAP治疗改善了对所有血管舒张剂的前臂血流（p = 0.01）。
伴有频繁夜间血氧饱和度下降的OSAHS患者存在内皮依赖性和非内皮依赖性血管舒张功能受损，这种受损与低氧血症程度成正比，且CPAP治疗可改善。血管功能受损为OSAHS的不良心血管后果奠定了潜在机制。
