臺灣博碩士論文加值系統

中文摘要
1 背景:
從過去的研究發現，阻塞型睡眠呼吸中止症的病人似乎有較高的機會得到心血管疾病，其中包括了高血壓、心律不整、新陳代謝症候群、冠狀動脈及腦血管疾病。其潛在的機轉主要有三個，分別是1. 缺氧導致交感神經的活化2. 血管內皮功能障礙 3. 全身系統性的發炎反應。
治療阻塞性睡眠呼吸中止症obstructive sleep apnea, OSA的首選是陽壓呼吸器continuous positive airway pressure, CPAP。使用陽壓呼吸器以後，對於阻塞性睡眠呼吸中止症OSA患者罹患高血壓或是頑固性高血壓，都可以降低血壓，且能降低心血管病併發症以及減少因為心血管引起的死亡。
然而，臨床上病人願意持續配戴陽壓呼吸器的比率不高。因此，臨床上考慮替代的治療方案，例如上呼吸道的手術、口腔裝置。而其中懸壅垂顎咽成形術uvulopalatopharyngoplasty, UPPP則是一種最常見的上呼吸道手術。UPPP在臨床上除了可以治療阻塞性睡眠呼吸中止症，同時亦有研究指出UPPP亦可以如同CPAP對於OSA病人一樣，可改善血壓，也可有效地減少鬱血性心臟衰竭和心房顫動的風險。
截至目前為止，並沒有太多的文獻對於UPPP在OSA病人上，對於重大心血管事件(包括急性心肌梗塞, 冠狀動脈粥樣硬化、心房顫動、心室顫動、心衰竭、中風)的預防功效做過評估，此外亦沒有探討對於OSA病人的慢性病是否有影響，如高血壓、糖尿病、心血管疾病(非重大心血管事件)、高血脂、慢性腎臟病疾病。

2 研究目的以及材料方法：
本研究為回溯性世代研究，回溯雙和醫院2009-2016的病歷資料，主要對象為阻塞性睡眠呼吸中止症OSA的病人，且有在雙和醫院接受多項睡眠生理檢查polysomnography, PSG者，研究者擬使用電子病歷追蹤到2020年，想要知道懸壅垂顎咽成形術對於阻塞性睡眠呼吸中止症的影響，分為3個子研究。
2.1 第一個子研究:評估手術對於重大心血管事件(包括急性心肌梗塞, 冠狀動脈粥樣硬化、心房顫動、心室顫動、心衰竭、中風)，是否具有預防效果。選取三組做比較，分別是UPPP、CPAP、以及未接受任何睡眠呼吸中止症相關治療的對照組，來評估UPPP相對於其他兩組，是否有所差異。
2.2 第二個子研究:評估手術對於高血壓，是否有預防效果。選取三組做比較，分別是UPPP、CPAP、以及未接受任何睡眠呼吸中止症相關治療的對照組，來評估相對於對照組，是否有所差異。
2.3 第三個子研究:評估手術對於阻塞性睡眠呼吸中止症相關的心血管共病症，如糖尿病、心血管疾病(非重大心血管事件)、高血脂、慢性腎臟病疾病，是否有預防效果。選取三組做比較，分別是UPPP、CPAP、以及未接受任何睡眠呼吸中止症相關治療的對照組，來評估相對於對照組，是否有所差異。
3 預期結果：
3.1 第一子研究:
 懸壅垂顎咽成形術相比於對照組，對於重大心臟不良事件有較好的預防效果。
 懸壅垂顎咽成形術相對於陽壓呼吸器，則是具有相似的保護效果。
3.2 第二子研究:
 懸壅垂顎咽成形術相比於對照組，對於高血壓有較好的預防效果。
 懸壅垂顎咽成形術相對於陽壓呼吸器，則是具有相似的保護效果。
3.3 第三子研究:
 懸壅垂顎咽成形術相比於對照組，在心血管相關的慢性病，如糖尿病、慢性腎臟病、心血管疾病、高血脂症具有較好的保護效果。

ABSTRACT
1 Background:
An accumulating body of evidence has shown obstructive sleep apnea (OSA) to be associated with a higher risk of cardiovascular diseases (CVD), including hypertension, arrythmia, metabolic syndrome, coronary artery disease, and cerebrovascular disease. OSA may cause disease through 3 potential mechanism included 1. hypoxemia-induced sympathetic activation, 2. endothelial dysfunction, and 3. systemic inflammation.
Clinically, CPAP is the first choice for OSA treatment. Randomized controlled trials have suggested that continuous positive airway pressure (CPAP) can lower blood pressures among hypertensive patients and the onset or death from cardiovascular complications.
However, the adherence of CPAP is sometimes poor. In such case, alternative options, such as upper airway surgery, oral devices may be considered in the treatment of OSA. Uvulopalatopharyngoplasty (UPPP) is the most common type of upper airway surgery. UPPP not only can treat obstructive sleep apnea, but also can improve blood pressure, and decrease the risk of congestive heart failure and atrial fibrillation in OSA patients, just like CPAP.
Review of the literature, the role of UPPP in OSA patients is not clear. Only a few articles mention the preventing effect of major at major adverse cardiac events (MACE), such as acute myocardial infarction, coronary artery sclerosis, atrial fibrillation, ventricular fibrillation, heart failure and stroke. Besides, the preventing effect of UPP for chronic morbidities of OSA patients, such as hypertension, diabetes mellitus, cardiovascular disease (not MACEs), hyperlipidemia, and chronic renal disease, is unknown.
2 Study aims and study design:
A retrospective cohort study will conduct with OSA patients to follow-up based medical charts in Shuang Ho Hospital (New Taipei City, Taiwan) between 2009 to 2016. Patients who older than 35 years old, received PSG at hospital, and diagnosed OSA will be included. According Electronic medical record, they will follow to 2020. We aim to figure out the role of UPPP in OSA for reducing the CVD risk. Therefore, we performed 2 studies.
2.1 First study aims to evaluate whether UPPP in OSA patients had a therapeutic effect in preventing major adverse cardiovascular events (MACEs), including acute myocardial infarction, coronary atherosclerosis, atrial fibrillation, ventricular fibrillation, heart failure and stroke. There were 3 groups: UPPP, CPAP and non-treatment group (control group).
2.2 Second study aims to evaluate whether UPPP can prevent hypertension. There were 3 groups: UPPP, CPAP and non-treatment group (control group).
2.3 Third study aims to evaluate whether UPPP can prevent cardiovascular-related comorbidities, such as diabetes mellitus, chronic kidney disease, cardiovascular disease and hyperlipidemia. There were 3 groups: UPPP, CPAP and non-treatment group (control group).



3 Expected research outcomes are as follows:
3.1 The first study:
 UPPP has a therapeutic effect in preventing cardiovascular events in patients with obstructive sleep apnea.
 UPPP had a similar preventive effect as CPAP.
3.2 The second study:
 UPPP can prevent the development of new-onset hypertension in patients with OSA.
 UPPP had a similar preventive effect as CPAP.
3.3 The third study:
 UPPP and CPAP have better preventive effect on DM, CVD, CKD, and hyperlipidemia.

目錄
Publication List 4
中文摘要 5
1 背景: 5
2 研究目的以及材料方法： 6
3 預期結果： 7
ABSTRACT 8
1 Background: 8
2 Study aims and study design: 9
3 Expected research outcomes are as follows: 10
第一章、 緒論 11
1. 研究背景與動機 11
2. 研究目的 13
第二章、 文獻回顧 14
1. 致病機轉以及名詞縮寫 14
1.1. 睡眠呼吸中止症的致病機轉 14
 心血管方面 14
 內分泌方面 14
 腎臟方面 15
 高血脂 15
1.2. 重要名詞以及縮寫 16
2. 重大心臟不良事件和心血管疾病 17
2.1. OSA病人的心血管風險 17
2.2. CPAP對於MACE的治療成效 18
2.3. UPPP治療對於MACE的治療成效 19
3. 高血壓 20
3.1. OSA病人的高血壓風險 20
3.2. CPAP治療對於高血壓的治療成效 21
3.3. UPPP治療對於高血壓的治療成效 21
4. 糖尿病 23
4.1. OSA病患的糖尿病風險 23
4.2. CPAP對於糖尿病的治療成效 23
4.3. UPPP對於糖尿病的治療成效 24
5. 慢性腎臟病 25
5.1. OSA患者的慢性腎臟病風險 25
5.2. CPAP 治療對於慢性腎臟病的治療成效 25
5.3. UPPP治療對於慢性腎臟病的治療成效 26
6. 高血脂 27
6.1. OSA病人的高血脂風險 27
6.2. CPAP治療對於高血脂的治療成效 27
6.3. UPPP治療對於高血脂的治療成效 28
7. 睡眠呼吸中止症的盛行率 29
8. 陽壓呼吸器的介紹 30
9. OSA的治療方式 34
9.1. 止鼾牙套 34
9.2. 口咽肌肉運動 35
9.3. Maxillomandibular advancement MMA上頜及下顎骨前移整型手術 37
10. 總結 40
第三章、 研究材料與方法 41
1 研究設計 41
2 研究對象 45
3 資料收集 46
4 暴露變項定義以及分組 47
5 追蹤定義以及相關內容 47
6 終點定義及相關內容 48
7 干擾因子以及其他變項說明 49
8 統計分析（包含資料特性以及分析假設） 50
第四章、 預計成果與貢獻 51
1 第一子研究: 重大心血管事件 51
2 第二子研究:高血壓 51
3 第三子研究:糖尿病，心血管疾病，慢性腎臟病，高血脂 52
第五章、 研究結果 53
1 第一子研究: 重大心血管事件 53
2 第二子研究: 高血壓 59
3 第三子研究: 其他心血管共病症 65
第六章、 討論 77
1 本研究主結果 77
2 研究結果之討論 79
3 陽壓呼吸器CPAP的遵從率 85
4 OSA的治療方式優劣討論 86
4.1 止鼾牙套 oral appliance 87
4.2 口咽肌肉運動 orofacial myofunctional therapy, OMT 89
4.3 Maxillomandibular advancement MMA上頜及下顎骨前移整型手術 90
5 研究限制 91
6 結論 92
7 未來研究方向 93
第七章、 參考文獻 94

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