乙酰唑胺可降低高血压伴阻塞性睡眠呼吸暂停患者的血压和睡眠呼吸紊乱：一项随机对照试验。
Acetazolamide Reduces Blood Pressure and Sleep-Disordered Breathing in Patients With Hypertension and Obstructive Sleep Apnea: A Randomized Controlled Trial.
机构信息
Center for Sleep and Vigilance Disorders, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Sleep Disorders Center, Pulmonary Department, Sahlgrenska University Hospital, Gothenburg, Sweden.
出版信息
J Clin Sleep Med. 2018 Mar 15;14(3):309-317. doi: 10.5664/jcsm.6968.
STUDY OBJECTIVES
The carbonic anhydrase inhibitor acetazolamide (AZT) modulates blood pressure at high altitude and reduces sleep-disordered breathing in patients with obstructive sleep apnea (OSA). We aimed to investigate the treatment effect of AZT and in combination with continuous positive airway pressure (CPAP) on blood pressure in patients with hypertension and OSA.
METHODS
In a prospective, randomized, three-way crossover study, 13 male patients with hypertension and moderate to severe OSA (age 64 ± 7 years, body mass index 29 ± 4 kg/m, and mean apnea-hypopnea index 37 ± 23 events/h) received AZT, CPAP, or AZT plus CPAP for 2-week periods. Antihypertensive medication was washed out. Office and 24-hour blood pressure, arterial stiffness, polygraphic sleep study data, and blood chemistry were compared.
RESULTS
AZT alone and AZT plus CPAP, but not CPAP alone, reduced office mean arterial pressure compared to baseline (-7 [95% CI -11 to -4], -7 [95% CI -11 to -4] and -1 [95% CI -5 to 4] mmHg, respectively; repeated- measures analysis of variance (RM-ANOVA; = .015). Aortic systolic pressure and augmentation index, assessed by radial artery oscillatory tonometry, were unaffected by CPAP but decreased after AZT and AZT plus CPAP (RM-ANOVA = .030 and .031, respectively). The apnea-hypopnea index was significantly reduced in all three treatment arms, most prominently by AZT plus CPAP (RM-ANOVA = .003). The reduction of venous bicarbonate concentration following AZT was correlated with the change of apnea-hypopnea index ( = 0.66, = .013).
CONCLUSIONS
AZT reduced blood pressure, vascular stiffness, and sleep-disordered breathing in patients with OSA and comorbid hypertension. Carbonic anhydrase inhibition may constitute a potential target for drug therapy in patients with sleep apnea and comorbid hypertension.
CLINICAL TRIAL REGISTRATION
Registry: ClinicalTrials.gov; Identifier: NCT02220803; Title: A Short Term Open, Randomized Cross-over Trial Exploring the Effect of Carbonic Anhydrase Inhibition by Acetazolamide on Sleep Apnea Associated Hypertension and Vascular Dysfunction; URL: https://clinicaltrials.gov/ct2/show/NCT02220803 and Registry: EU Clinical Trials Register; EudraCT Number: 2013-004866-33; Title: A short term open, randomized cross over trial exploring the effect of carbonic anhydrase inhibition by acetazolamide on sleep apnea associated hypertension; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004866-33.
研究目的
碳酸酐酶抑制剂乙酰唑胺（AZT）可调节高原地区的血压，并降低阻塞性睡眠呼吸暂停（OSA）患者的睡眠呼吸障碍。我们旨在研究 AZT 联合持续气道正压通气（CPAP）治疗对高血压合并 OSA 患者血压的影响。
方法
在一项前瞻性、随机、三向交叉研究中，13 名患有高血压和中重度 OSA 的男性患者（年龄 64 ± 7 岁，体重指数 29 ± 4 kg/m，平均呼吸暂停低通气指数 37 ± 23 次/小时）接受 AZT、CPAP 或 AZT+CPAP 治疗 2 周。洗脱抗高血压药物。比较诊室和 24 小时血压、动脉僵硬度、多导睡眠图数据和血液化学。
结果
AZT 单独和 AZT+CPAP 均能降低与基线相比的诊室平均动脉压（分别为-7[95%CI-11 至-4]和-7[95%CI-11 至-4]mmHg；重复测量方差分析（RM-ANOVA； =.015）。主动脉收缩压和增强指数通过桡动脉振荡张力测量不受 CPAP 影响，但 AZT 和 AZT+CPAP 后降低（RM-ANOVA 分别为.030 和.031）。所有三种治疗方法均显著降低了呼吸暂停低通气指数，以 AZT+CPAP 最为显著（RM-ANOVA 分别为.003）。AZT 后静脉碳酸氢盐浓度的降低与呼吸暂停低通气指数的变化相关（ = 0.66， =.013）。
结论
AZT 降低了 OSA 合并高血压患者的血压、血管僵硬和睡眠呼吸障碍。碳酸酐酶抑制可能成为治疗睡眠呼吸暂停合并高血压患者的潜在靶点。
临床试验注册
ClinicalTrials.gov；注册号：NCT02220803；标题：短期开放、随机交叉试验探索乙酰唑胺对睡眠呼吸暂停相关高血压和血管功能障碍的影响；网址：https://clinicaltrials.gov/ct2/show/NCT02220803；欧盟临床试验注册；EudraCT 编号：2013-004866-33；标题：短期开放、随机交叉试验探索乙酰唑胺对睡眠呼吸暂停相关高血压的影响；网址：https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-004866-33。
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