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研究生:葉姿麟
研究生(外文):Tzu-Lin Yeh
論文名稱:代謝健康/不健康之肥胖/過重與心血管疾病風險間的關係:台灣具代表性的世代研究
論文名稱(外文):Association between Metabolically Healthy/Unhealthy Obesity/overweight and the Risk of Cardiovascular Disease: A Representative Cohort Study in Taiwan
指導教授:簡國龍簡國龍引用關係
口試委員:李文宗季瑋珠林宇旋黃麗卿
口試日期:2020-05-20
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:流行病學與預防醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:89
中文關鍵詞:代謝健康肥胖代謝症候群心血管疾病三高主題資料庫社區前瞻性世代研究
外文關鍵詞:Metabolically healthy obesitymetabolic syndromecommunity-based prospective cohort studyy on HypertensionHyperglycemiaand Hyperlipidemia databasescardiovascular disease
DOI:10.6342/NTU202000958
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目的:探討台灣代謝健康肥胖者(Metabolically healthy obesity, MHO)/代謝不健康肥胖者(Metabolically unhealthy obesity, MUO)之和心血管疾病(Cardiovascular disease, CVD)風險間的關係,並探討潛在的修飾因子(effect modifiers)。

方法:三高主題資料庫是台灣具全國代表性的社區前瞻性世代研究。本研究將身體質量指數(body mass index, BMI)區分為:體重過輕( BMI < 18.5 kg/m2)、正常體重(BMI 18.5至23.9 kg/m2)和肥胖/過重(BMI ≥24 kg/m2)。無糖尿病、高血壓、高血脂症且實驗室數據符合以下定義為代謝健康:(1)空腹三酸甘油酯 <150 mg/dL;(2)男性高密度脂蛋白膽固醇 ≥40 mg/dL或女性高密度脂蛋白膽固醇 ≥50 mg/dL;(3)空腹血糖 <100 mg/dL;(4)收縮壓 <130且舒張壓 <85 mmHg;反之則為代謝不健康。研究終點是CVD發生率及死亡率。本研究使用Cox迴歸模型估計風險比(hazard ratio, HRs)和95%信賴區間(confidence interval, CI),並進行分層分析(subgroup analysis)及多種敏感度分析。

結果:5,719名受試者年齡平均值(標準差)為44.0 (15.5)歲,50.2%為女性,其中1,479名為參考組(代謝健康正常體重者),493名為MHO,MHO組之年齡平均為43.3歲,女性比例為47.1%;1,718名為MUO,MUO組之年齡平均為48.8歲,女性比例為39.6%。MHO在台灣20歲以上非懷孕、無已知心血管疾病中的盛行率為8.6%,佔所有肥胖族群之22.2%。在追蹤中位數(四分位差)13.7 (13.6-13.8)年間,共發生了449個CVD事件,其中MHO組發生了25個,MUO組發生了228個CVD事件。MHO組經多變項調整後之HR,相較於參考組顯著增加了75%的CVD風險,95% CI為1.02-2.99;MUO組經多變項調整後之HR(95% CI)為3.10 ( 2.09-4.60)。分層分析顯示女性MHO組CVD HR為4.69,男性為1.14,女性MUO組CVD HR為8.86,男性為2.03;低於65歲MHO組CVD HR為4.28,大於等於65歲MHO組CVD HR為1.87。敏感度分析結果多穩健地顯示出MHO顯著增加CVD風險。

結論:無論目前代謝健康與否,肥胖均顯著增加了CVD風險,MHO者仍顯著增加了CVD風險,我們鼓勵所有肥胖之族群,即使目前代謝狀況健康,都應積極維持體重,以避免將來之CVD風險。
Aims: To investigate the relationship between individuals with metabolically healthy obesity (MHO) /metabolically unhealthy obesity (MUO) and the cardiovascular disease (CVD) risk in Taiwan and to explore potential effect modifiers.

Methods: Participants from the Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia databases, a nationwide representative community-based prospective cohort study in Taiwan were recruited, and classified into three body mass index (BMI) categories: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5 to 23.9 kg/m2), and obesity/overweight (BMI ≥24 kg/m2). Participants without diabetes, hypertension, hyperlipidemia and had healthy metabolic profiles (1) fasting triglyceride <150 mg/dL; (2) high-density lipoprotein cholesterol ≥40 mg/dL in men or ≥50 mg/dL in women; (3) fasting glucose <100 mg/dL; (4) systolic blood pressure <130 and diastolic blood pressure <85 mmHg were defined as metabolically health. Our endpoints were CVD mortality and morbidity. Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CI) by Cox regression analysis were performed. Subgroup analyses and several sensitivity analyses were done.

Results: A total of 5,719 participants with mean (standard deviation) age 44.0 (15.5) years old, 50.2% women was recruited. Among the total participants, 1,479 individuals were metabolically healthy normal weight (the reference group), 493 participants were the MHO group with the mean age 43.3 years old and women percentage 47.1% and 1,718 participants were the MHO group with the mean age 48.8 years old and women percentage 39.6%. The prevalence of MHO was 8.6% among non-pregnancy, CVD-free, aged equal or over 20 years old population, MHO accounts for 22.2% in obese participants. During a median (interquartile range) follow-up time of 13.7 (13.6-13.8) years, 449 ascertained CVD events developed, 25 CVD events developed in the MHO group and 228 CVD events developed in the MUO group. Compared with the reference group, MHO had a significant higher CVD risk, adjusted HR with 95% CI was 1.75 (1.02-2.99), MUO also had a significant higher CVD risk, adjusted HR(95% CI) 3.10 ( 2.09-4.60). Subgroup analysis showed women with MHO had an adjusted CVD HR of 4.69, men with MHO had a HR of 1.14 and women with MUO had an adjusted CVD HR of 8.86, men with MHO had a HR of2.03. MHO participants younger than 65 years old had an adjusted CVD HR of 1.74, elderly with MHO had an adjusted CVD HR of 1.87; MUO participants younger than 65 years old had an adjusted CVD HR of 4.28, elderly with MHO had an adjusted CVD HR of 1.87Sensitivity analyses revealed robust and significant higher CVD risk in different MHO scenarios.

Conclusions: Despite of current metabolic status, obesity had a significantly higher risk for CVD. MHO also increased the risk. Aggressive body weight control, even in current metabolically healthy status, is mandatory for CVD control.
目錄
致謝 ii
中文摘要 iii
英文摘要 v
第一章 研究背景 1
第一節 心血管疾病(Cardiovascular disease, CVD) 1
第二節 代謝健康肥胖 (Metabolically healthy obesity, MHO) 2
第三節 MHO與CVD之文獻回顧 4
1.3.1 過去文獻回顧 4
1.3.2 台灣MHO文獻回顧 5
1.3.3 研究缺口 6
第二章 研究目的與假說 7
第三章 研究方法 8
第一節 研究架構 8
3.1.1 三高主題資料庫 8
3.1.2 受試者之選取 9
第二節 研究設計 9
3.2.1 MHO之操作型定義 9
3.2.2 CVD之操作型定義 10
3.2.3 共變項之操作型定義 11
第三節 統計方法 11
3.3.1 樣本數計算 11
3.3.2 描述性統計 11
3.3.3 分析性統計 12
3.3.4 附加分析 13
3.3.4.1 分層分析 13
3.3.4.2 敏感度分析 13
第四章 結果 16
第一節 描述性分析結果 16
第二節 分析性統計結果 17
第三節 分層分析結果 18
4.3.1 性別分層分析結果 18
4.3.2 年齡分層分析結果 19
4.3.3 吸菸分層分析結果 20
4.3.4 代謝與BMI狀態分互作用分析結果 21
第四節 敏感度分析結果 21
4.4.1 以腰圍重新定義中心型肥胖 21
4.4.2 排除首年事件 21
4.4.3 以校正BMI重新定義肥胖 22
4.4.4 重新定義代謝健康 22
第五章 討論 24
第一節 主要結果概述 24
第二節 比較過去文獻 24
第三節 生物機轉 27
第四節 公共衛生及臨床應用 27
第五節 優勢與限制 28
5.5.1 研究優勢 28
5.5.2 研究限制 28
第六節 結論 29
Tables 30
I. Tables of literature review 30
II. Tables of definitions in the study cohort 42
III. Tables of results 50
Figures 57
參考文獻 62
附錄 77
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