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研究生:賴瑩荷
研究生(外文):Ying-Ho Lai
論文名稱:鉀鎂的營養狀況與死亡率以及神經功能表現之關係
論文名稱(外文):The relationship between potassium and magnesium status and health outcomes: mortality and neurological performance
指導教授:潘文涵潘文涵引用關係
口試委員:白其卉林石化許重義陳俊榮
口試日期:2015-04-25
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生化科技學系
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:中文
論文頁數:147
中文關鍵詞:血鉀心血管死亡率老人中風含鉀含鎂低鈉鹽神經功能表現
外文關鍵詞:Serum potassiumcardiovascular mortalityelderlystrokepotassium and magnesium-enriched saltneurological performance
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腦中風為重大傷病,會導致死亡及神經功能受損,日常活動甚至是生活品質都會因為神經功能缺損而受到影響。礦物質營養素,鉀、鎂在腦中風以及其兩大危險因子,高血壓和糖尿病之致病機轉中均扮演重要角色。飲食當中攝取過多的鈉會使血壓上升及增加中風的風險,鉀的補充具有降低血壓及中風風險的作用,鎂的缺乏和糖尿病發生率成顯著相關,在中風初期投予鎂是否有長期神經保護的作用,也是當前熱門的議題。然而以長期維持營養的概念管理高危險人群,如:老人與中風患者之鉀鎂營養狀況以改善其預後,尚缺乏深入之研究。

研究一、血鉀和老人死亡率的相關性(前瞻性世代研究)

背景/目的:已有研究報告指出血鉀濃度和已存在心血管疾病和腎功能受損 (pre-existing cardiovascular disease and impaired renal function) 的病人的不良事件呈負相關,但在社區老人 (community-based elderly individuals),血鉀正常範圍值是否太寬和其不良事件的關係尚未被詳細研究。目的:本研究針對社區老人來檢驗低和高正常血鉀值 (low- and high-normal serum potassium) 和心血管疾病及全死因死亡率的相關性。方法:使用2個獨立的台灣老人社區世代 (community cohorts) 之前瞻性研究 (perspective study) (n=2065),其血鉀值介於2.8-5.6 mmol/L。本研究將個案分成4組,低血鉀 (low serum potassium, 2.8-3.4 mmol/L)、正常低血鉀 (low-normal serum potassium, 3.4–3.8 mmol/L)、正常血鉀 (normal serum potassium, 3.9–4.4 mmol/L)、及正常高血鉀 (high-normal serum potassium, 4.5–5.6 mmol/L)。我們使用Cox proportional hazards model來比較不同血鉀組和死亡率的相關性。結果:基線血鉀和所有死因及心血管疾病死亡率呈現U型的關係,而血鉀落在3.9到4.4 mmol/L之間病人的死亡率最低。和正常血鉀相比,正常低血鉀組其全死因 (HR, 1.3; 95% CI, 1.0–1.6) 及心血管疾病死亡率 (HR, 1.6; 95% CI, 1.1–2.3) 顯著較高。正常高血鉀組死亡率較正常血鉀組高,但未達統計上的顯著意義。結論:根據本研究結果,我們建議正常低血鉀亦可作為老人存活預後較差的警示指標。



研究二、含鉀含鎂低鈉鹽介入對中風患者癒後的影響 (多中心臨床試驗)

背景/目的:低血鎂是糖尿病風險以及腦中風嚴重度之指標,近年來針對急性梗塞性中風病人靜脈注射硫酸鎂之研究受到相當重視,但結果並不肯定。本研究室先前針對榮民之家的社區老人,長期進行含鉀低鈉鹽取代一般食鹽之介入研究,發現可以降低41%的心血管疾病死亡率。食鹽是一個好的礦物質載體,本研究,擬進一步探討,以食鹽為載體,長期改善鉀和鎂的營養,是否能夠更進一步,改善中風病人之預後。目的:本研究目的為評估含鉀含鎂低鈉鹽對中風病人神經功能表現的影響。方法:本多中心臨床試驗,包括三個組別:一般食鹽組、含鉀低鈉鹽組、和含鉀含鎂低鈉鹽組。我們在個案出院時及回診時提供適量的食鹽,並自收案起持續追蹤個案的NIHSS、Barthel Index (BI) 及mRS至6個月,若個案的mRS≦1會被視為較佳的神經功能指標。我們以Generalized Estimating Equations (GEE) 來檢驗食鹽的使用和神經功能的相關性,並校正年齡、性別和用藥。結果:和基線相比,不論是在第三個月 (3rd month) 或第六個月 (6th month) 回診時,含鉀含鎂低鈉鹽組其個案mRS≦1的比例顯著較一般食鹽組及含鉀低鈉鹽組高 (3rd month: p=0.01, 0.03或6th month: p=0.005, 0.01)。和一般食鹽相比,含鉀含鎂低鈉鹽組可以顯著增加中風病人神經功能表現的勝算比 (odds ratio, 1.8; p=0.035)。結論:本研究建議,長期管理腦中風病人之鎂營養狀況可以改善中風病人的神經功能表現,在病人未能有效提升飲食鎂攝食量時,含鎂含鉀低鈉鹽為一有效礦物質鎂的添加載體。



Stroke is among the leading causes of death, which can cause to permanent neurological deficits and affect quality of life. Potassium and magnesium, two essential minerals, play important roles in the pathogenesis of hypertension, diabetes, and stroke. Dietary sodium excess contributes to the blood pressure elevation with age and increases the risk of stroke. Potassium can counteract the effect of sodium on hypertension and protect against stroke mortality. Magnesium nutriture has been associated with diabetes risk and severity of stroke symptom. Intravenous provision of magnesium to acute phase stroke patients has been vigorously studied but with controversial findings. It is lacking studies to investigate the association between nutritional status of these minerals and the long-term cerebrovascular outcomes of high risk groups such as elderly and stroke patients.

Study 1. Association study between serum potassium and risk of cardiovascular and all-cause death in community-based elderly (Prospective study)

Background/Purpose: Several studies have already reported that serum potassium (SK) correlated inversely with adverse event among patients with pre-existing cardiovascular disease and impaired renal function; less is known about the prognostic value of SK at the normal range in community-based elderly individuals. Objective: This study aimed to examine whether low normal or high normal SK value was associated with cardiovascular and all-cause mortalities in elderly people. Methods: Perspective study using two independent elderly Taiwanese community cohorts which included 2065 subjects with relatively normal SK values (2.8-5.6 mmol/L). Subjects were grouped into: low (2.8-3.4 mmol/L), low-normal SK (3.5–3.8 mmol/L), normal (3.9–4.4 mmol/L), and high-normal SK (4.5–5.6 mmol/L). Proportional hazards model was applied to compare the association between SK concentration groups and mortality. Results: The relationship between baseline SK and all-cause and cardiovascular mortality was U-shaped, with the lowest mortality rates observed in patients with SK levels of 3.9 to 4.4 mmol/L. The low-normal SK group had significantly higher risk of all-cause (HR, 1.3; 95% CI, 1.0–1.6) and cardiovascular mortalities (HR, 1.6; 95% CI, 1.1–2.3) than the normal SK group. The high normal SK group had higher but non-significant risk compared to the normal. Conclusion: Our findings suggest that low-normal SK may be used as a marker of poor survival for elderly outpatient cares.



Study 2. The effect of intervention with potassium and/ or magnesium-enriched salt on neurological performance of stroke patients (Multi-center clinical trial)

Background: Stroke is one of the leading causes of mortality and neurological deficits. Adequate dietary potassium is associated with reduced risk of hypertension and stroke. Our previous 3.5-year intervention trial in the elderly demonstrated a 41%-reduction in cardiovascular mortality from switching to potassium-enriched salt. Since dietary magnesium has been associated with lowered diabetes/stroke risk in human and neuroprotection in animal and salt is a good carrier for mineral; it is justifiable to study whether further enriching salt with magnesium may provide additional benefit for stroke recovery, at the level near but not beyond the daily recommended intake level (DRI). Methods: A multi-centered randomized controlled trial was carried out with three arms: (1) regular salt (Na salt), (2) potassium-enriched salt (K salt), and (3) potassium and magnesium-enriched salt (K/Mg salt). The NIHSS, Barthel Index (BI) and mRS were evaluated at baseline, 3 month, and 6 month. Results: A significantly higher percentage of patients with mRS≦1was observed for both the K/Mg and the K groups at 3rd (p=0.01 and 0.03, respectively) and 6th months (p=0.005 and 0.01) than baseline. This phenomenon is not apparent in the Na group. The K/Mg group had a significantly increased odds ratio of achieving good neurological performance defined by a combination of 3 indices, compared with the Na group (odds ratio, 1.77; p=0.035) and with the K group (odds ratio, 1.70; p-0.057). Conclusion: This study suggests that long-term replenishing magnesium to reach DRI is beneficial for stroke patients to recover from neurological injuries.



目 錄

中文摘要………………………………………………………………………….... 1
英文摘要………………………………………………………………………….... 3
第一章 前言………………………………………………………………….…... 6
第二章 文獻回顧………………………………………………………………… 7
第一節 腦中風的分類及診斷……………………………………………… 7
第二節 中風後功能恢復評估工具………………………………………… 9
第三節 中風的危險因子………………………………………………….. 12
第四節 各類中風最初症狀……………………………………………….. 17
第三章 中風病人相關用藥………………………………………………………. 18
第一節 糖尿病藥物……………………………………………………….. 18
第二節 高血壓藥物……………………………………………………….. 19
第三節 降血脂藥物……………………………………………………….. 21
第四節 cyclooxygenease抑制劑 (Aspirin)………………………………. 22
第四章 鈉、鉀和鎂與心臟血管疾病關係的相關文獻探討………………….. 23
第一節 鈉對血壓的影響的相關機轉…………………………………….. 23
第二節 鉀和鎂對血壓的影響的相關機轉……………………………….. 23
第三節 鉀和中風相關的動物模式研究………………………………….. 24
第四節 血鉀和死亡率的相關性………………………………………….. 25
第五節 飲食鈉、鉀和心血管疾病的相關研究…………………………… 25
第六節 血鎂和代謝症候群及中風的相關研究………………………….. 26
第七節 飲食鎂和代謝症候群的相關研究……………………………….. 26
第八節 飲食鎂和血壓的相關研究……………………………………….. 27
第九節 飲食鎂和中風的相關研究………………………………………… 27
第五章 鎂與腦神經健康關係的文獻探討…………………………………….. 29
第一節 鎂對梗塞性中風的神經保護機轉……………………………….. 29
第二節 鎂對神經表現影響的相關研究………………………………….. 30
第六章 減鹽試驗的相關研究………………………………………………….. 34
第一節 減鹽飲食控制法與血壓………………………………………….. 34
第二節 含鉀低鈉鹽類之介入…………………………………………….. 34
第三節 含鉀含鎂低鈉之鹽類飲食介入………………………………….. 35
第四節 飲食中的鈉、鉀及鎂攝取量與尿液中鈉、鉀及鎂離子的相關性.. 36
第七章 台灣地區民眾的飲食鉀、鈉、鎂的攝取量………………………….. 38
第一節 鉀的攝取量……………………………………………………….. 38
第二節 鈉的攝取量……………………………………………………….. 38
第三節 國內糖尿病盛行率與鎂攝取量的關係………………………….. 39
第四節 本研究訂定低鈉鹽中適量的鉀及鎂含量的參考依據………….. 39
第八章 研究動機與目的……………………………………………………….. 41
第九章 研究方法……………………………………………………………….. 42
第一節 Low-normal serum potassium is associated with increased risk of cardiovascular and all-cause death in community-based elderly…………….. 42
第二節 The effect of intervention with potassium and/ or magnesium-enriched salt on neurological performance of stroke patients………………………… 55
第十章 研究結果……………………………………………………………….. 68
第一節 Low-normal serum potassium is associated with increased risk of cardiovascular and all-cause death in community-based elderly……………. 69
第二節 The effect of intervention with potassium and/ or magnesium-enriched salt on neurological performance of stroke patients………………………… 86
第十一章 總結………………………………………………………………… 103
參考文獻…………………………………………………………….…………... 105
附錄一 National Institutes of Health Stroke Scale……………………………. 120
附錄二 Barthel Index/ Modified Rankin Scale….…………………………….. 121
附錄三 同意書………………………………………………………………… 122
附錄四 (A) 中央研究院醫學研究倫理委員會研究計畫審查同意書……… 129
附錄四 (B) 財團法人彰化基督教醫院同意臨床試驗證明書………………. 130
附錄四 (C) 國立台灣大學醫學院附設醫院臨床試驗許可書………………. 132
附錄四 (D) 中山醫學大學附設醫院臨床試驗計畫許可書………………… 133
附錄四 (E) 財團法人新光吳火獅紀念醫院同意臨床試驗證明書…………. 134
附錄四 (F) 財團法人奇美醫院人體試驗委員會同意臨床試驗證明書……. 135
附錄四 (G) 財團法人私立高雄醫學大學附設醫院同意臨床試驗證明書… 136
附錄四 (H) 長庚醫療財團法人人體試驗委員會同意臨床試驗證明書…… 137
附錄四 (I) 中國醫藥大學附設醫院人體試驗計畫同意書………………….. 138
附錄四 (J) 台北榮民總醫院同意臨床試驗證明書………………………….. 139
附錄五 (A) 問卷-NIHSS / Barthel index and MRS………………………….. 140
附錄五 (B) 問卷-藥物史記錄單……………………………………………... 141
附錄五 (C) 問卷-血液尿液生化檢測值登錄單……………………………... 142
附錄五 (D) 問卷-飲食頻率問卷……………………………………………... 143
附錄五 (E) 問卷-再住院原因………………………………………………... 144
附錄五 (F) 問卷-中風登錄表………………………………………………… 145
附錄五 (G) 問卷-死因報告表………………………………………………... 146
附錄五 (H) 問卷-個案退出計畫通知書……………………………………... 147


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中文參考文獻

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VIII.潘文涵、張雅惠、吳幸娟、張新儀、魏燕蘭、李美璇、高美丁、杭極敏(http://obesity.hpa.gov.tw/TC/researchList.aspx?pn=1&cid=166)台灣地區老人營養健康狀況調查1999-2000:以二十四小時飲食回顧法評估老人膳食營養狀況。P21-34,衛生福利部國民健康署,台北市。
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國民營養健康狀況變遷調查1993-1996:以二十四小時飲食回顧法評估國人膳食營養狀況。P37-52,衛生福利部國民健康署,台北市。
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XIII.翁履珍、鄭裕耀、葉乃華、金惠民、潘文涵 (2006) 使用鉀點數表提高飲食鉀攝取量。臺灣營養學會雜誌31(4):pp. 102-116。



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