本文選題：持續(xù)氣道正壓通氣 + 阻塞性睡眠呼吸暫停��； 參考：《北京協(xié)和醫(yī)學院》2016年博士論文

【摘要】：第一部分：持續(xù)氣道正壓通氣治療阻塞性睡眠呼吸暫停低通氣綜合征合并高血壓對家庭血壓及靶器官損害的影響背景及目的：阻塞性睡眠呼吸暫停低通氣綜合征與高血壓有明確的相關(guān)性,持續(xù)氣道正壓通氣治療是中重度阻塞性睡眠呼吸暫停低通氣綜合征的一線治療方式。既往關(guān)于持續(xù)氣道正壓通氣治療對阻塞性睡眠呼吸暫停低通氣綜合征合并高血壓的降壓效應(yīng)多以診室血壓和動態(tài)血壓為終點,而基于物聯(lián)網(wǎng)技術(shù)的家庭自測血壓干預可顯著降低患者的血壓。本研究以家庭自測血壓為研究終點,旨在探索基于物聯(lián)網(wǎng)技術(shù)的持續(xù)氣道正壓通氣治療對阻塞性睡眠呼吸暫停低通氣綜合征合并高血壓患者家庭血壓治療效果,以及對其靶器官損害的影響。方法：在該隨機對照臨床研究中,將120例中重度阻塞性睡眠呼吸暫停合并高血壓的患者(75歲)以1：1的比例隨機分為持續(xù)氣道正壓通氣組(CPAP組)與非CPAP組,兩組均給予家庭血壓監(jiān)測儀,通過芯片實現(xiàn)數(shù)據(jù)實時傳輸。主要終點是隨訪12月時兩組家庭血壓下降值的比較。結(jié)果：共12例患者失訪(非CPAP組7例,CPAP組5例),隨訪12月時的結(jié)果如下：校正后CPAP組的家庭平均白天血壓和平均夜間血壓下降值分別為21.5mmHg(95%可信區(qū)間：19.0,24.0)/6.2mmHg(95%可信區(qū)間：3.7,8.8)和6.0mmHg(95%可信區(qū)間：2.5,9.5)/3.7mmHg(95%可信區(qū)間：0.9,6.5),非CPAP組校正后的家庭平均白天血壓和平均夜間血壓下降值分別為15.6mmHg(95%可信區(qū)間：13.1,18.2)/5.1mmHg(95%可信區(qū)間：2.5,7.7)和-1.6mmHg(95%可信區(qū)間：-5.1,2.0)/-3.5mmHg(95%可信區(qū)間：-6.6,-0.6)。兩組家庭平均白天血壓下降值的差值是5.9mmHg(95%可信區(qū)間：2.3,9.5)/1.2mmHg(95%可信區(qū)間：-2.6,4.9),P值：收縮壓0.002,舒張壓0.543；兩組家庭平均夜間血壓下降值的差值是7.6mmHg(95%可信區(qū)間：2.5,12.6)/7.2mmHg(95%可信區(qū)間：3.1,11.3),P值：收縮壓0.004,舒張壓0.001。CPAP組平均踝臂脈搏波速下降值(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)和平均左室質(zhì)量指數(shù)下降值(22.5±7.6 g/m2)均顯著高于非CPAP組(2.3±1.3m/s,P0.001：9.2±25.9 mg/g,P=0.003；9.8±10.1 g/m2,P0.001)。結(jié)論：基于物聯(lián)網(wǎng)技術(shù)的持續(xù)氣道正壓通氣治療可顯著降低阻塞性睡眠呼吸暫停低通氣綜合征合并高血壓患者的家庭血壓,改善靶器官損害。第二部分：螺內(nèi)酯治療阻塞性睡眠呼吸暫停低通氣綜合征合并難治性高血壓的療效研究背景及目的：難治性高血壓中阻塞性睡眠呼吸暫停綜合征與高醛固酮血癥患病率均很高,阻塞性睡眠呼吸暫停的嚴重程度與醛固酮水平有正相關(guān)性。既往的自身對照試驗發(fā)現(xiàn)螺內(nèi)酯治療可改善阻塞性睡眠呼吸暫停合并難治性高血壓的呼吸暫停低通氣指數(shù),亦可有效降低血壓。本研究為隨機對照臨床試驗,旨在探討螺內(nèi)酯治療對中重度阻塞性睡眠呼吸暫停合并難治性高血壓的療效。方法：在該隨機對照臨床研究中,將30例中重度阻塞性睡眠呼吸暫停合并難治性高血壓的患者(30-70歲)以1：1的比例隨機分為試驗組(在原有降壓藥的基礎(chǔ)上加用螺內(nèi)酯20 mg/天,隨訪4周時如診室血壓仍≥140/90mmHg則改為40mg/天)與對照組(空白對照)。主要終點是隨訪12周時兩組呼吸暫停低通氣指數(shù)下降值的比較。結(jié)果：隨訪12周時試驗組(n=15例)校正后的平均呼吸暫停低通氣指數(shù)下降值顯著高于對照組：17.5次/h(95%可信區(qū)間：11.7,23.3)vs.0.5次/h(95%可信區(qū)間：-5.3,6.3),平均呼吸暫停低通氣指數(shù)下降值在兩組間的差值為17.0次/h(95%可信區(qū)間：8.6,25.5),P0.001。試驗組平均呼吸暫停指數(shù)和平均氧減指數(shù)下降值均顯著高于對照組(P=0.016;P=0.001),平均最低血氧飽和度及平均血氧飽和度升高值均顯著高于對照組(P=0.028；P0.001)。試驗組平均診室血壓下降值為22.2±9.5/11.3±8.6mmHg,對照組為10.0±6.9/3.3±6.3mmHg, P分別為收縮壓0.001,舒張壓=0.007。平均動態(tài)血壓下降值均顯著高于對照組(P均0.05)。該研究未出現(xiàn)螺內(nèi)酯相關(guān)不良反應(yīng)。結(jié)論：螺內(nèi)酯能顯著降低合并難治性高血壓的中重度阻塞性睡眠呼吸暫停的嚴重程度,降低血壓水平。螺內(nèi)酯可成為不能行持續(xù)氣道正壓通氣治療的患者的可選方案。第三部分：381例大動脈炎合并高血壓的臨床特點及治療背景及目的：大動脈炎是繼發(fā)性高血壓的重要因素之一,而高血壓是大動脈炎最常見的并發(fā)癥,也是大動脈炎的預后相關(guān)因素。既往關(guān)于大動脈炎相關(guān)高血壓的研究多為一些個案報道或小樣本研究。本文旨在中國一大樣本大動脈炎患者中系統(tǒng)分析大動脈炎表現(xiàn)為高血壓的臨床特點、治療及預后。方法：回顧性分析2004年1月-2014年12月在阜外醫(yī)院住院的381例表現(xiàn)為高血壓的大動脈炎患者。高血壓的診斷依據(jù)外周血壓或中心動脈壓。結(jié)果：381例大動脈炎表現(xiàn)為高血壓的患者中,腎動脈狹窄(264例,69.3%)最常見,其次是降主動脈狹窄(98例,25.7%)、腹主動脈狹窄(78例,20.5%)和嚴重主動脈瓣返流(45例,11.8%),98例(25.7%)患者有兩種或兩種以上的原因。發(fā)現(xiàn)高血壓的平均年齡為25.0±14.3歲,219例(57.5%)患者以高血壓為首發(fā)臨床表現(xiàn),73例(19.2%)患者高血壓發(fā)病年齡18歲。無雙側(cè)鎖骨下動脈狹窄的321例(84.3%)患者平均上肢血壓是176.0±29.4 mmHg/97.2±23.0 mmHg,雙側(cè)鎖骨下動脈狹窄的60例(15.7%)患者外周血管造影時測得主動脈根部壓力平均為192.7±30.8mmHg/102.4±121.1 mmHg。305例(80.1%)患者平均隨訪38.4±36.7月,血壓控制率、改善率和失敗率分別是50.8%、41.0%和8.2%。Logistic回歸分析示免疫抑制治療(OR值：2.402,95%可信區(qū)間：1.253-4.603,P=0.008)和引起高血壓的受累血管部位(P=0.010)與高血壓控制預后顯著相關(guān)。結(jié)論：大動脈炎引起高血壓的機制非常復雜,同一患者可有多種因素同時出現(xiàn),腎動脈狹窄最為常見,其次是胸降主動脈狹窄、腹主動脈狹窄和重度慢性主動脈’瓣返流。免疫抑制治療和大動脈炎引起高血壓的受累血管部位與血壓控制預后顯著相關(guān)。第四部分：274例大動脈炎合并神經(jīng)系統(tǒng)癥狀臨床特點及預后分析背景及目的：大動脈炎的神經(jīng)系統(tǒng)表現(xiàn)是多樣化的,與累及血管的部位和數(shù)量密切相關(guān),腦卒中是大動脈炎最嚴重的并發(fā)癥之一。國內(nèi)外缺乏關(guān)于大動脈炎以神經(jīng)系統(tǒng)癥狀為表現(xiàn)的大樣本研究。本研究旨在中國一單中心較大樣本量大動脈炎人群中分析大動脈炎合并神經(jīng)系統(tǒng)癥狀的臨床特點及預后情況。方法：回顧性分析我院2002年1月-2013年11月住院的大動脈炎患者(610例),篩選出合并神經(jīng)系統(tǒng)癥狀的患者,收集分析其臨床特點、影像學資料及預后情況。神經(jīng)系統(tǒng)癥狀包括：頭暈、頭痛、視力下降或失明、暈厥、腦血管事件(短暫性腦缺血發(fā)作和腦卒中)。結(jié)果：共274例(44.9%)患者入選,男女比例1：4.3,平均發(fā)病年齡是28.2±11.2歲,平均延遲診斷時間是52.4±5.5月。最常見的神經(jīng)系統(tǒng)表現(xiàn)為頭暈(214,78%),其次是頭痛70例(25.5%)、暈厥60例(21.9%),視力下降或失明和短暫性腦缺血發(fā)作均為58例(21.2%),共30例(10.9%)腦卒中(缺血性卒中27例,出血性卒中2例,缺血性+出血性卒中1例)。暈厥、腦血管事件、視力下降或失明與疾病活動性顯著正相關(guān)(P值分別是0.001、0.018、0.001)。最常見的分型為Ⅲ型(廣泛型)112例(40.9%),弓上動脈最常累及左鎖骨下動脈147例(53.6%)。頭暈與鎖骨下動脈受累和椎動脈受累有相關(guān)性(χ2=10.845,P=0.001；χ2=6.789,P=0.009)。視力下降或失明和頸總動脈受累有相關(guān)性(χ2=6.239,P=0.012)。短暫性腦缺血發(fā)作與鎖骨下動脈受累有相關(guān)性(χ2=17.924,P0.001)。缺血性卒中和頸總動脈狹窄閉塞有相關(guān)性(χ2=10.290,P=0.001),而出出血性卒中見于腹主動脈和/或腎動脈狹窄閉塞者。175例(63.9%)患者平均隨訪3.7±0.3年(0.27年～10.8年),心衰是最常見死亡原因,并且是存活人群中最常見的心血管事件。結(jié)論：神經(jīng)系統(tǒng)癥狀在大動脈炎病人中有多種表現(xiàn),與累及動脈部位相關(guān)。缺血性卒中與弓上動脈狹窄閉塞性病變有關(guān),出血性卒中與繼發(fā)性腎動脈或腹主動脈狹窄所致高血壓有關(guān)。
[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.

【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R766;R544.1;R543.5
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本文編號：1836658