慢性间歇低氧对阻塞性睡眠呼吸暂停低通气综合征患者血压的影响

目的 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者的慢性间歇低氧对血压和NO/内皮素水平的影响.方法 选取2006年6月至8月于北京大学人民医院呼吸科就诊的18岁以上OSAHS患者、该院慢性阻塞性肺疾病(COPD)患者协会的稳定期COPD患者及健康志愿者85例,根据问卷调查、常规肺功能检查和多导睡眠监测结果分为OSAHS不吸烟组、OSAHS吸烟组、COPD组和健康对照组.测量多导睡眠监测当晚睡前和次日晨起(简称晨起睡前)静息状态血压,采用硝酸还原酶法测定晨起血清中和晨起睡前呼出气冷凝液中NO浓度,放射免疫法测定晨起血清内皮素浓度.计量资料采用方差分析,计数资料采用x2检验,正态分布数据采用Pearson相关分析,非正态分布数据采用Spearman相关分析,并进行多元线性回归分析.结果 OSAHS组晨起舒张压升高幅度不吸烟组(88±10)mm Hg,吸烟组(95±17)mm Hg,1 mm Hg=0.133 kPa]明显大于COPD组(76±7)mm Hg]和对照组(70±6)mm Hg];OSAHS组晨起睡前呼出气冷凝液中NO浓度差值不吸烟组(-4.5±7.9)μmol/L,吸烟组(-3.4±5.5)μmol/L]明显低于COPD组(1.4±6.1)μmol/L]和对照组(3.1±4.0)μmol/L];OSAHS吸烟组血清NO/内皮素(1.0±0.5)明显低于COPD组(1.4±0.7).控制了性别、年龄、体重指数、颈围、吸烟史、饮酒史、高血压级别、服用高血压药种类后,晨起睡前NO浓度差值与舒张压差值呈负相关,与呼吸暂停低通气指数(AHI)呈正相关;晨起睡前舒张压差值与AHI、脉搏氧饱和度(SpO2)＜90%的氧减幅度、SpO2＜90%的氧减梯度呈负相关.多元线性回归分析结果显示,AHI每增加1次/h,晨起舒张压较睡前增加0.41 mm Hg;晨起睡前NO浓度差值每增加1 μmol/L,晨起睡前舒张压差值减少0.27 mm Hg;AHI每增加1次/h,晨起睡前NO浓度差值增加0.40 μmol/L.结论 OSAHS患者晨起舒张压较睡前明显升高,晨起睡前呼出气冷凝液中NO浓度变化可以间接反映机体NO消耗情况,并与OSAHS病情显著相关,与晨起睡前舒张压变化相关.

The effect of chronic intermittent hypoxia caused by obstructive sleep apnea hypopnea syndrome on blood pressure

OBJECTIVE: To explore the effect of chronic intermittent hypoxia caused by obstructive sleep apnea hypopnea syndrome (OSAHS) and chronic continuous hypoxia caused by chronic obstructive pulmonary disease (COPD) on blood pressure and levels of nitric oxide (NO)/endothelin (ET). METHODS: A total of 85 cases were selected, including OSAHS patients over 18 years old visited this hospital from June to August 2006, stable COPD patients and healthy volunteers. According to the results of clinical questionnaire, pulmonary function test and polysomography (PSG), they were divided into 4 groups: non-smoking OSAHS patients (n = 26), smoking OSAHS patients (n = 22), patients with stable COPD (n = 17) and healthy control subjects (n = 20). Blood pressure measurement was performed before and after the PSG examination while the subjects were resting. The levels of ET and NO in blood samples and exhaled breath condensates (EBC) were measured by radioimmunoassay and nitrate reductase, respectively. Measurement data were analyzed by ANOVA, numeration data were analyzed by chi-square test, data of normal distribution were analyzed by Pearson correlation analysis, and non-normal data were analyzed by Spearman correlation analysis. Multiple linear regression analysis was also performed. RESULTS: Regardless of the smoking status, the difference of morning-evening diastolic blood pressure (DBP) in the morning of patients with OSAHS non-smoking OSAHS: (88 +/- 10) mm Hg, 1 mm Hg = 0.133 kPa; smoking OSAHS: (95 +/- 17) mm Hg] was higher than that of patients with COPD (76 +/- 7) mm Hg] and healthy subjects (70 +/- 6) mm Hg]. The difference of morning-evening NO level in EBC of patients with OSAHS non-smoking OSAHS: (-4.5 +/- 7.9) micromol/L; smoking OSAHS: (-3.4 +/- 5.5) micromol/L] was lower than that of patients with COPD (1.4 +/- 6.1) micromol/L] and healthy subjects (3.1 +/- 4.0) micromol/L]. The ratio of NO to ET in serum of the smoking OSAHS group (1.0 +/- 0.5) was lower than that of the COPD group (1.4 +/- 0.7). After adjustment for sex, age, BMI, waist circumference, history of smoking and alcohol, level of hypertension, and category of antihypertensive drugs, the morning-evening difference of NO level in EBC was negatively associated with the morning-evening difference of DBP (r = -0.301, P = 0.021), and was positively associated with apnea hypopnea index (AHI) (r = 0.116, P < 0.05). The morning-evening difference of DBP was associated with AHI (r = -0.303, P = 0.011), amplitude of oxygen desaturation with pulse oxygen saturation (SpO(2)) less than 90% (OLA90%, r = -0.281, P = 0.018), and gradient of oxygen desaturation with SpO(2) less than 90% (OLG90%, r = 0.286, P = 0.035). Multiple linear regression analysis showed that, if AHI increased by 1/h, the morning-evening difference of DBP would increase 0.41 mm Hg; if the morning-evening difference of NO level in EBC increased by 1 micromol/L, the morning-evening difference of DBP would decrease 0.27 mm Hg; and if AHI increased by 1/h, the morning-evening difference of NO level in EBC would increase 0.40 micromol/L. CONCLUSION: The DBP of OSAHS patients in the morning is significantly higher than that in the evening. The morning-evening difference of NO level in EBC reflects indirectly the consumption of NO in the body, and is associated with the degree of OSAHS and the morning-evening difference of DBP.