高血压伴阻塞性睡眠呼吸暂停低通气综合征的治疗及大动脉炎与高血压的临床特征研究

发布时间：2018-05-03 03:01

  本文选题：持续气道正压通气 + 阻塞性睡眠呼吸暂停　； 参考：《北京协和医学院》2016年博士论文

【摘要】：第一部分：持续气道正压通气治疗阻塞性睡眠呼吸暂停低通气综合征合并高血压对家庭血压及靶器官损害的影响背景及目的：阻塞性睡眠呼吸暂停低通气综合征与高血压有明确的相关性,持续气道正压通气治疗是中重度阻塞性睡眠呼吸暂停低通气综合征的一线治疗方式。既往关于持续气道正压通气治疗对阻塞性睡眠呼吸暂停低通气综合征合并高血压的降压效应多以诊室血压和动态血压为终点,而基于物联网技术的家庭自测血压干预可显著降低患者的血压。本研究以家庭自测血压为研究终点,旨在探索基于物联网技术的持续气道正压通气治疗对阻塞性睡眠呼吸暂停低通气综合征合并高血压患者家庭血压治疗效果,以及对其靶器官损害的影响。方法：在该随机对照临床研究中,将120例中重度阻塞性睡眠呼吸暂停合并高血压的患者(75岁)以1：1的比例随机分为持续气道正压通气组(CPAP组)与非CPAP组,两组均给予家庭血压监测仪,通过芯片实现数据实时传输。主要终点是随访12月时两组家庭血压下降值的比较。结果：共12例患者失访(非CPAP组7例,CPAP组5例),随访12月时的结果如下：校正后CPAP组的家庭平均白天血压和平均夜间血压下降值分别为21.5mmHg(95%可信区间：19.0,24.0)/6.2mmHg(95%可信区间：3.7,8.8)和6.0mmHg(95%可信区间：2.5,9.5)/3.7mmHg(95%可信区间：0.9,6.5),非CPAP组校正后的家庭平均白天血压和平均夜间血压下降值分别为15.6mmHg(95%可信区间：13.1,18.2)/5.1mmHg(95%可信区间：2.5,7.7)和-1.6mmHg(95%可信区间：-5.1,2.0)/-3.5mmHg(95%可信区间：-6.6,-0.6)。两组家庭平均白天血压下降值的差值是5.9mmHg(95%可信区间：2.3,9.5)/1.2mmHg(95%可信区间：-2.6,4.9),P值：收缩压0.002,舒张压0.543；两组家庭平均夜间血压下降值的差值是7.6mmHg(95%可信区间：2.5,12.6)/7.2mmHg(95%可信区间：3.1,11.3),P值：收缩压0.004,舒张压0.001。CPAP组平均踝臂脉搏波速下降值(4.9±±2.8m/s)、平均尿微量白蛋白/肌酐比值下降值(38.1±55.2 mg/g)和平均左室质量指数下降值(22.5±7.6 g/m2)均显著高于非CPAP组(2.3±1.3m/s,P0.001：9.2±25.9 mg/g,P=0.003；9.8±10.1 g/m2,P0.001)。结论：基于物联网技术的持续气道正压通气治疗可显著降低阻塞性睡眠呼吸暂停低通气综合征合并高血压患者的家庭血压,改善靶器官损害。第二部分：螺内酯治疗阻塞性睡眠呼吸暂停低通气综合征合并难治性高血压的疗效研究背景及目的：难治性高血压中阻塞性睡眠呼吸暂停综合征与高醛固酮血症患病率均很高,阻塞性睡眠呼吸暂停的严重程度与醛固酮水平有正相关性。既往的自身对照试验发现螺内酯治疗可改善阻塞性睡眠呼吸暂停合并难治性高血压的呼吸暂停低通气指数,亦可有效降低血压。本研究为随机对照临床试验,旨在探讨螺内酯治疗对中重度阻塞性睡眠呼吸暂停合并难治性高血压的疗效。方法：在该随机对照临床研究中,将30例中重度阻塞性睡眠呼吸暂停合并难治性高血压的患者(30-70岁)以1：1的比例随机分为试验组(在原有降压药的基础上加用螺内酯20 mg/天,随访4周时如诊室血压仍≥140/90mmHg则改为40mg/天)与对照组(空白对照)。主要终点是随访12周时两组呼吸暂停低通气指数下降值的比较。结果：随访12周时试验组(n=15例)校正后的平均呼吸暂停低通气指数下降值显著高于对照组：17.5次/h(95%可信区间：11.7,23.3)vs.0.5次/h(95%可信区间：-5.3,6.3),平均呼吸暂停低通气指数下降值在两组间的差值为17.0次/h(95%可信区间：8.6,25.5),P0.001。试验组平均呼吸暂停指数和平均氧减指数下降值均显著高于对照组(P=0.016;P=0.001),平均最低血氧饱和度及平均血氧饱和度升高值均显著高于对照组(P=0.028；P0.001)。试验组平均诊室血压下降值为22.2±9.5/11.3±8.6mmHg,对照组为10.0±6.9/3.3±6.3mmHg, P分别为收缩压0.001,舒张压=0.007。平均动态血压下降值均显著高于对照组(P均0.05)。该研究未出现螺内酯相关不良反应。结论：螺内酯能显著降低合并难治性高血压的中重度阻塞性睡眠呼吸暂停的严重程度,降低血压水平。螺内酯可成为不能行持续气道正压通气治疗的患者的可选方案。第三部分：381例大动脉炎合并高血压的临床特点及治疗背景及目的：大动脉炎是继发性高血压的重要因素之一,而高血压是大动脉炎最常见的并发症,也是大动脉炎的预后相关因素。既往关于大动脉炎相关高血压的研究多为一些个案报道或小样本研究。本文旨在中国一大样本大动脉炎患者中系统分析大动脉炎表现为高血压的临床特点、治疗及预后。方法：回顾性分析2004年1月-2014年12月在阜外医院住院的381例表现为高血压的大动脉炎患者。高血压的诊断依据外周血压或中心动脉压。结果：381例大动脉炎表现为高血压的患者中,肾动脉狭窄(264例,69.3%)最常见,其次是降主动脉狭窄(98例,25.7%)、腹主动脉狭窄(78例,20.5%)和严重主动脉瓣返流(45例,11.8%),98例(25.7%)患者有两种或两种以上的原因。发现高血压的平均年龄为25.0±14.3岁,219例(57.5%)患者以高血压为首发临床表现,73例(19.2%)患者高血压发病年龄18岁。无双侧锁骨下动脉狭窄的321例(84.3%)患者平均上肢血压是176.0±29.4 mmHg/97.2±23.0 mmHg,双侧锁骨下动脉狭窄的60例(15.7%)患者外周血管造影时测得主动脉根部压力平均为192.7±30.8mmHg/102.4±121.1 mmHg。305例(80.1%)患者平均随访38.4±36.7月,血压控制率、改善率和失败率分别是50.8%、41.0%和8.2%。Logistic回归分析示免疫抑制治疗(OR值：2.402,95%可信区间：1.253-4.603,P=0.008)和引起高血压的受累血管部位(P=0.010)与高血压控制预后显著相关。结论：大动脉炎引起高血压的机制非常复杂,同一患者可有多种因素同时出现,肾动脉狭窄最为常见,其次是胸降主动脉狭窄、腹主动脉狭窄和重度慢性主动脉’瓣返流。免疫抑制治疗和大动脉炎引起高血压的受累血管部位与血压控制预后显著相关。第四部分：274例大动脉炎合并神经系统症状临床特点及预后分析背景及目的：大动脉炎的神经系统表现是多样化的,与累及血管的部位和数量密切相关,脑卒中是大动脉炎最严重的并发症之一。国内外缺乏关于大动脉炎以神经系统症状为表现的大样本研究。本研究旨在中国一单中心较大样本量大动脉炎人群中分析大动脉炎合并神经系统症状的临床特点及预后情况。方法：回顾性分析我院2002年1月-2013年11月住院的大动脉炎患者(610例),筛选出合并神经系统症状的患者,收集分析其临床特点、影像学资料及预后情况。神经系统症状包括：头晕、头痛、视力下降或失明、晕厥、脑血管事件(短暂性脑缺血发作和脑卒中)。结果：共274例(44.9%)患者入选,男女比例1：4.3,平均发病年龄是28.2±11.2岁,平均延迟诊断时间是52.4±5.5月。最常见的神经系统表现为头晕(214,78%),其次是头痛70例(25.5%)、晕厥60例(21.9%),视力下降或失明和短暂性脑缺血发作均为58例(21.2%),共30例(10.9%)脑卒中(缺血性卒中27例,出血性卒中2例,缺血性+出血性卒中1例)。晕厥、脑血管事件、视力下降或失明与疾病活动性显著正相关(P值分别是0.001、0.018、0.001)。最常见的分型为Ⅲ型(广泛型)112例(40.9%),弓上动脉最常累及左锁骨下动脉147例(53.6%)。头晕与锁骨下动脉受累和椎动脉受累有相关性(χ2=10.845,P=0.001；χ2=6.789,P=0.009)。视力下降或失明和颈总动脉受累有相关性(χ2=6.239,P=0.012)。短暂性脑缺血发作与锁骨下动脉受累有相关性(χ2=17.924,P0.001)。缺血性卒中和颈总动脉狭窄闭塞有相关性(χ2=10.290,P=0.001),而出出血性卒中见于腹主动脉和/或肾动脉狭窄闭塞者。175例(63.9%)患者平均随访3.7±0.3年(0.27年～10.8年),心衰是最常见死亡原因,并且是存活人群中最常见的心血管事件。结论：神经系统症状在大动脉炎病人中有多种表现,与累及动脉部位相关。缺血性卒中与弓上动脉狭窄闭塞性病变有关,出血性卒中与继发性肾动脉或腹主动脉狭窄所致高血压有关。
[Abstract]:The first part: the background and purpose of the effect of continuous positive airway pressure ventilation in the treatment of obstructive sleep apnea hypopnea syndrome with hypertension on family blood pressure and target organ damage: obstructive sleep apnea hypopnea syndrome has a clear correlation with hypertension. Continuous positive airway pressure ventilation is a medium to severe obstructive sleep. The first line treatment of apnea hypopnea syndrome. The antihypertensive effect of continuous positive airway pressure ventilation treatment on obstructive sleep apnea hypopnea syndrome with hypertension is mostly the end of the blood pressure and ambulatory blood pressure in the consulting room, while the family self-measured blood pressure intervention based on the Internet of things technique can significantly reduce the blood pressure of the patients. The purpose of this study was to explore the effect of continuous positive airway pressure therapy on family blood pressure in patients with obstructive sleep apnea hypopnea syndrome combined with hypertension, and the effect on target organ damage in patients with obstructive sleep apnea hypopnea syndrome. Methods: in this randomized controlled clinical study, 120 cases were used in this randomized controlled clinical study. The patients with severe obstructive sleep apnea and hypertension (75 years old) were randomly divided into the continuous positive airway pressure group (CPAP group) and non CPAP group at the proportion of 1:1, and the two groups were given family blood pressure monitor to achieve real-time data transmission through the chip. The main end point was the comparison between the two groups of family blood pressure drop values in the two groups in December. Results: a total of 12 Cases (7 cases in non CPAP group and 5 cases in group CPAP) were followed up for December. The average daytime blood pressure and mean nocturnal blood pressure drop values in the CPAP group were 21.5mmHg (95% confidence interval: 19.0,24.0) /6.2mmHg (95% confidence interval: 3.7,8.8) and 6.0mmHg (95% confidence interval: 2.5,9.5) /3.7mmHg (95% confidence interval: 0.9,6) .5), the average daytime blood pressure and the mean nocturnal blood pressure drop value after correction in the non CPAP group were 15.6mmHg (95% confidence interval: 13.1,18.2) /5.1mmHg (95% confidence interval: 2.5,7.7) and -1.6mmHg (95% confidence interval: -5.1,2.0) /-3.5mmHg (95% confidence interval: -6.6, -0.6). The difference between the average daytime blood pressure drop values of the two groups was 5.9mmHg (9) 5% confidence interval: 2.3,9.5) /1.2mmHg (95% confidence interval: -2.6,4.9), P value: systolic pressure 0.002, diastolic pressure 0.543; the difference of average night blood pressure drop value of two families was 7.6mmHg (95% confidence interval: 2.5,12.6) /7.2mmHg (95% confidence interval: 3.1,11.3), P value: systolic pressure 0.004, and diastolic pressure 0.001.CPAP group average ankle arm pulse wave speed decline The value (4.9 + + 2.8m/s), the decrease of mean urine microalbumin / creatinine ratio (38.1 + 55.2 mg/g) and the mean left ventricular mass index decreased (22.5 + 7.6 g/m2) were significantly higher than those in the non CPAP group (2.3 + 1.3m/s, P0.001:9.2 + 25.9 mg/g, P=0.003; 9.8 + 10.1 g/m2, P0.001). Reducing the family blood pressure in patients with obstructive sleep apnea hypopnea syndrome with hypertension and improving target organ damage. The second part: the background and objective of the study of the efficacy of spironolactone in the treatment of obstructive sleep apnea hypopnea syndrome with refractory hypertension: obstructive sleep apnea syndrome in refractory hypertension The prevalence of hyperaldosterone and high aldosterone is very high. The severity of obstructive sleep apnea is positively correlated with the levels of aldosterone. Previous self controlled trials have found that spironolactone can improve the apnea hypopnea index in obstructive sleep apnea with refractory hypertension and also effectively reduce blood pressure. The purpose of this randomized controlled clinical trial was to explore the efficacy of spironolactone therapy for moderate to severe obstructive sleep apnea with refractory hypertension. In this randomized controlled clinical study, 30 patients (30-70 years old) with moderate to severe obstructive sleep apnea and refractory hypertension were randomly divided into an experimental group (in the original 1:1) On the basis of the antihypertensive drugs, adding spironolactone 20 mg/ days, followed up for 4 weeks, if the blood pressure in the consulting room was still more than 140/90mmHg to 40mg/ days, and the control group (blank control). The main end point was the comparison of the two groups of apnea hypopnea index at 12 weeks' follow-up. Results: the average apnea hypopnea after correction of the test group (n=15 cases) was followed up for 12 weeks. The index descending value was significantly higher than that of the control group: 17.5 /h (95% confidence interval: 11.7,23.3) vs.0.5 /h (95% confidence interval: -5.3,6.3), and the difference between the average apnea hypopnea index in two groups was 17 /h (95% confidence interval: 8.6,25.5), and the average apnea index and the decrease of average oxygen subtraction index in P0.001. test group were both significant Compared with the control group (P=0.016; P=0.001), the average oxygen saturation and the increase of average blood oxygen saturation were significantly higher than those in the control group (P=0.028; P0.001). The mean blood pressure drop value in the experimental group was 22.2 + 9.5/11.3 8.6mmHg, the control group was 10 + 6.9/3.3 + 6.3mmHg, P was 0.001 of systolic blood pressure and diastolic pressure =0.007. mean ambulatory blood pressure. The drop value was significantly higher than that in the control group (P 0.05). The study did not appear to be a spironolactone associated adverse reaction. Conclusion: spironolactone can significantly reduce the severity of moderate to severe obstructive sleep apnea with refractory hypertension and reduce blood pressure. Spironolactone may be an alternative to patients who cannot be treated with continuous positive airway pressure ventilation. The third part: the clinical characteristics and treatment background and purpose of 381 cases of Takayasu's arteritis with hypertension: Takayasu arteritis is one of the important factors of secondary hypertension, and hypertension is the most common complication of Takayasu arteritis and also the prognostic factors of Takayasu arteritis. The systematic analysis of Takayasu's arteritis in a large sample of Takayasu's arteritis in a large sample of China is the clinical characteristics of hypertension, treatment and prognosis. Methods: a retrospective analysis of 381 cases of Takayasu arteritis in Fuwai Hospital in December -2014 January 2004. The diagnostic basis of hypertension. Peripheral blood pressure or central arterial pressure. Results: among 381 patients with Takayasu's manifestation of hypertension, renal artery stenosis (264 cases, 69.3%) was the most common, followed by descending aortic stenosis (98 cases, 25.7%), abdominal aortic stenosis (78 cases, 20.5%) and severe aortic regurgitation (45, 11.8%), 98 (25.7%) patients and more than 98 or two reasons. The average age of hypertension was 25 + 14.3 years, 219 cases (57.5%) had hypertension as the first clinical manifestation, 73 (19.2%) patients aged 18 years of hypertension. The average upper limb blood pressure in 321 cases without double side subclavian artery stenosis (84.3%) was 176 + 29.4 mmHg/97.2 + 23 mmHg, bilateral subclavian artery stenosis of 60 cases (15.7%) The average aortic root pressure was 192.7 + 30.8mmHg/102.4 + 121.1 mmHg.305 (80.1%) patients (80.1%) were followed up for 38.4 + 36.7 months. The control rate of blood pressure, improvement rate and failure rate were 50.8%, 41%, and 8.2%.Logistic regression analysis (OR value: 2.402,95% confidence interval: 1.253-4.603, P=0.008) and caused by immunosuppressive therapy. The vascular location of hypertension (P=0.010) is significantly related to the prognosis of hypertension control. Conclusion: the mechanism of hypertension caused by Takayasu's arteritis is very complicated. There are many factors in the same patient, the most common renal artery stenosis is, the next is the stenosis of the thoracic aorta, the stenosis of the abdominal aorta and the severe chronic aortic regurgitation. The vascular location of hypertension caused by Takayasu's arteritis and Takayasu's arteritis is closely related to the prognosis of blood pressure control. Fourth part: the clinical characteristics and prognosis of 274 cases of Takayasu's arteritis with nerve system symptoms and prognostic analysis background and objective: the nervous system manifestations of Takayasu arteritis are diversified, closely related to the location and quantity of the vessels involved. Stroke is one of the most serious complications of Takayasu's arteritis. There is a lack of large sample studies on the manifestation of Takayasu's arteritis with nervous system symptoms. This study aims to analyze the clinical specificity and prognosis of Takayasu arteritis in a single center large sample of Takayasu's arteritis in China. Methods: retrospective analysis The patients with Takayasu's arteritis (610 cases) hospitalized in November -2013 January 2002 were selected to select the patients with the symptoms of the nervous system to collect and analyze their clinical features, imaging data and prognosis. The symptoms of the nervous system include dizziness, headache, decline of vision or blindness, syncope, cerebral vascular events (transient ischemic attacks and stroke). A total of 274 (44.9%) patients were selected. The proportion of men and women was 1:4.3, the average age of onset was 28.2 + 11.2 years, the average delayed diagnosis time was 52.4 + 5.5 months. The most common nervous system was dizziness (214,78%), followed by headache in 70 cases (25.5%), syncope in 21.9% (21.9%), decreased vision or blindness and transient ischemic attack in 58 cases (21.2%), altogether 30 cases ( 10.9%) cerebral apoplexy (27 cases of ischemic stroke, 2 cases of hemorrhagic stroke, 1 cases of ischemic + hemorrhagic stroke). Syncope, cerebral vascular events, visual loss or blindness were positively correlated with disease activity (P value was 0.001,0.018,0.001, respectively). The most common types were type III (40.9%), and 147 cases of superior subclavian artery frequently involved in upper arch artery. 53.6%). Correlativity is associated with the involvement of the subclavian artery and the involvement of the vertebral artery (x 2=10.845, P=0.001; Chi 2=6.789, P=0.009). Visual loss or blindness is associated with the involvement of the common carotid artery (x 2=6.239, P=0.012). Transient ischemic attacks are associated with subclavian artery involvement (x 2=17.924, P0.001). Ischemic stroke and common carotid artery stenosis Occlusion was correlated (x 2=10.290, P=0.001), and hemorrhagic stroke was seen in abdominal aorta and / or renal artery stenosis (63.9%) patients (63.9%) with an average follow-up of 3.7 + 0.3 years (0.27 years to 10.8 years). Heart failure was the most common cause of death and was the most common cardiovascular event in the surviving population. Conclusion: the symptoms of the nervous system in the Takayasu arteritis. Multiple manifestations of the patient are associated with the involvement of the arterial location. Ischemic stroke is associated with occluded occluded lesions of the upper arch artery. Hemorrhagic stroke is associated with hypertension caused by secondary renal arteries or abdominal aortic stenosis.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R766;R544.1;R543.5
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本文编号：1836658