睡眠主要功能為恢復個人白天活動後所損耗之體能，調整和重組人之情緒行為和認知記憶，睡眠同時影響中樞神經、血流、呼吸、新陳代謝等各方面之變化，因此睡眠失調將有害身心健康。失眠為一種常見疾病，可由睡眠障礙與精神疾病、循環系統疾病或胃腸道疾病所引起之合併症狀。失眠為易感染心血管和腦血管等疾病之危險因素。研究顯示超過50％之中風患者擁有睡眠呼吸中止問題，多數睡眠呼吸障礙屬於阻塞性睡眠呼吸暫停，多項研究上顯示睡眠呼吸中止為引起心血管疾病和腦血管疾病之危險因素。以往岡維西等人發現，剝奪健康人們之睡眠會造成急性血壓升高與交感神經系統活動失常。而減少睡眠時間可能會導致罹患高血壓。近來研究也表明失眠將可能導致動脈粥樣硬化。

然而比較失眠種類不同，是否會影響特定疾病患病風險上升之研究較少。本研究將20歲以上失眠病患分為睡眠呼吸中止失眠與非睡眠呼吸中止失眠病患。比較非睡眠呼吸中止失眠病患與睡眠呼吸中止失眠病患，罹患急性心肌梗塞與腦中風疾病之風險比率。
急性心肌梗塞為冠狀動脈血流突然因血栓而完全阻斷，導致臨床出現心肌缺氧同時並有心肌壞死現象。腦中風之類型包括腦梗塞、腦出血、暫時性腦缺血發作，腦中風為患者因腦部血流受阻，導致無法正常供應腦部需求氧氣。急性心肌梗塞與腦中風皆為急症，儘管現代醫學進步，急性心肌梗塞與腦中風死亡率依然居高不下。睡眠呼吸中止失眠患者因不易查覺擁有呼吸中止症狀，往往誤以非睡眠呼吸中止失眠來尋求診療，造成錯誤治療，導致病情加重，提高罹患心血管疾病和腦血管疾病風險。

本文評估非睡眠呼吸中止失眠與睡眠呼吸中止失眠對急性心肌梗塞與腦中風發病風險比上差異。研究樣本為臺灣全國人口為基礎之隊列研究，原始數據來自臺灣之全民健康保險研究資料庫（NHIRD），追查2004-2010年非睡眠呼吸中止失眠與睡眠呼吸中止失眠病患，比較兩群組間年齡、性別、合併病症等相關風險因素，進而探討出非睡眠呼吸中止失眠與睡眠呼吸中止失眠患者罹患急性心肌梗塞與腦中風之危險因子與風險。

於2004-2010年間共尋獲非睡眠呼吸中止失眠病患153929人次。睡眠呼吸中止失眠4671人次。合併病症方面睡眠呼吸中止失眠併發高血壓、糖尿病、高脂血症、肥胖症，所占百分比均比非睡眠呼吸中止失眠病患為高。性別、年齡、合併病症所占兩群族比例，用成卡方檢定檢測出p 值皆<0.0001，証實兩群組合併症狀所占比例明顯差異，適合將年齡、性別、合併病症狀做為引發急性心肌梗塞與腦中風之危險因子。利用Cox’s proportional hazard，計算兩群組罹患急性心肌梗塞與腦中風風險比，發現睡眠呼吸中止失眠病患較易非睡眠呼吸中止失眠容易罹患腦中風(HR = 1.12; 95% CI = 1.03-1.21)。利用Kaplan-Meier curves做出之急性心肌梗塞與腦中風患病趨勢圖，皆顯示初經過年份月久，睡眠呼吸中止失眠病患都有較高機率罹患急性心肌梗塞與腦中風。

Insomnia is a common complaint in general population. The association is clear between sleep disorders (SD) and comorbidities such as prior psychiatric disorders, prior circulatory diseases and prior gastrointestinal diseases. Conversely, insomnia may predispose patients to cardiovascular and cerebrovascular risk. More than 50% of stroke patients have sleep-disordered breathing, mostly in the form of obstructive sleep apnea, which is recognized as an independent risk factor for cardiovascular diseases (CVD) and cerebrovascular diseases (CVA). Gangwisch et al found that depriving healthy people of sleep acutely raises blood pressure and sympathetic nervous system activity. Prolonged short sleep durations could lead to hypertension. Recent studies have also shown insomnia to be associated with atherosclerosis risk. However, studies investigating the possibility that non-apnea SD and sleep apnea insomnia (SA) may increase cerebrovascular diseases (CVA) are scant.

Acute myocardial infarction (AMI) results from the interruption of blood supply to a part of the heart muscle, which causes ischemia ensuing oxygen shortage, and the heart cells to be damaged or die. CVA types, including stroke, transient ischaemic attack, subarachnoid haemorrhage, vascular dementia, is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. AMI and CVA are life-threatening disorders that retain high morbidity and mortality despite advances in treatment. This thesis evaluates the effect of non-apnea SD and SA on the development of AMI and CVA among adults in Taiwan.

The thesis results are from a nationwide population-based cohort study assessing the possibilities of comparison of CVA and AMI risk among patients with SA, non-apnea SD. The original data were derived from Taiwan’s National Health Insurance Research Database (NHIRD). We conducted Cox’s proportional hazard regression analysis to estimate the effects of non-apnea sleep disorders and SA on CVA and AMI risk. Finally, The Kaplan-Meier curves are utilized to plot the freedom from AMI and CVA in both cohorts

By adjusting probable risk factors, the hazard ratio (HR) of AMI and CVA both increased with age and with comorbidity in both cohorts. After adjusting for demographic factors and comorbidities, the incidence of developing CVA increased 12% in SA patients. The Kaplan-Meier curves show that SA patients have higher chance to get AMI and CVA than the non-apnea SD patients with the time increasing.

論文審定書 i
誌謝 ii
中文摘要 iii
英文摘要 v
圖目錄 ix
表目錄 x
第一章 簡介 1
1.1背景與目的 1
1.2全民健康保險研究數據庫 3
1.3國際疾病分類 5
第二章相關研究 7
2.1 失眠盛行率 7
2.1.1 國際上失眠盛行率 7
2.1.2 台灣之失眠盛行率 7
2.2 失眠之定義 8
2.2.1 失眠種類 8
2.2.2 呼吸中止失眠簡介 9
2.3 失眠所引發疾病 11
第三章 研究方法 13
3.1資料來源 13
3.2研究設定 14
3.3研究架構 14
3.4 資料處理及統計方法 16
3.4.1 發生比率Incidence rate 16
3.4.2 Kaplan-Meier curve 17
3.4.3 Log-rank test 18
3.4.4 卡方測定 19
3.4.5 Cox proportional hazard Regression Model 21
3.4.6 95％信賴區間 22
第四章 實驗結果 24
4.1 失眠人口與合併症狀分佈 24
4.2 失眠族群於急性心肌梗塞存活分析 25
4.3 失眠族群於腦中風存活分析 27
第五節 討論 29
參考文獻 32
附錄 36
附錄1-1 門診處方及治療明細檔(適用85~92年) 36
附錄1-2 門診處方及治療明細檔(適用93年以後) 40
附錄1-3 門診處方醫令明細檔(適用86~95年) 44
附錄1-4 門診處方醫令明細檔(適用86~95年) 45
附錄1-5住院醫療費用清單明細檔(適用85~92年) 47
附錄1-6 住院醫療費用清單明細檔(適用83~95年) 52
附錄1-7 住院醫療費用清單明細檔(適用96年以後) 57
附錄1-8 承保資料檔(適用98年前) 62
附錄1-9 承保資料檔(適用99年以後) 63

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