臺灣博碩士論文加值系統

背景 WHO/ISH高血壓最新治療指引認為；除某些特定適應症外，六大類降壓藥均可作為高血壓治療第一線用藥。然而，如何根據臨床症狀選擇最有效的降壓藥，目前仍無研究。
目的 我們嘗試利用傳統醫學之辨證分型，對原發性高血壓患者比較其胰島素阻抗、左心室心肌質量、血液動力學和左心室舒張功能之差異，同時觀察其對Angiotension II blocker治療之療效。
方法 2001年12月到2003年1月期間在高雄市健仁醫院心臟科就診之原發性高血壓病患者，年齡30-80歲，從未接受治療，或近三個月未服用過降血壓藥物者，均被納入此一研究。依傳統中醫學證型分為陽亢型與痰濕壅盛型，測定胰島素與C-peptide濃度，所有病人一律接受心臟超音波之檢查。病人每天早晨均給予Valsartan治療，採用居家血壓自我測量的方法，來評估病人對治療之反應。
結果 陽亢型高血壓病人有較低的胰島素值(7.98 ±4.27 vs 11.39 ±9.54, P=0.033)及胰島素阻抗，較小的左心室質量(187.78±56.82 vs 220.59±74.74, P=0.02)、收縮末期容量(91.62±26.42 vs 104.21±31.79, P=0.03)與舒張末期容量(28.99±10.66 vs 35.55±14.35, P=0.01)，較低的收縮期心室壁張力(2839.61±456.27 vs 3123.66±608.09, P=0.01)，較短的E wave deceleration time(0.19±0.04 vs 0.20±0.04, P=0.04)。治療四週後，陽亢型病人與痰濕壅盛型相比，收縮壓(137.02 ± 14.62 mmHg vs 147.43 ± 12.63 mmHg, P=0.001)與舒張壓(137.02 ± 14.62 mmHg vs 147.43 ± 12.63 mmHg, P=0.001)間有顯著差異(P= 0.012)。且隨年齡增加，陽亢型病人出現isolated systolic hypertension的可能性較大。
結論 根據傳統醫學體質分類，原發性高血壓病人至少可被分為陽亢型與痰濕中阻型兩類，他們具有不同之胰島素值、胰島素阻抗、左心室質量、收縮末期容量、舒張末期容量、收縮期心室壁張力和E wave deceleration time。同時對Valsartan治療陽亢型高血壓病人有較好的反應。故陽亢型高血壓病人可以Valsartan作為第一線治療首選藥物；相對的，痰濕中阻型高血壓病人則需另選其他類之降血壓藥。

Background Drugs from all six main classes of anti-hypertensive agents are effective in lowering blood pressure, with no substantive differences between drug classes in effects on blood pressure. However, how to choice the best effective drug for hypertensive patients according clinic symptoms are not available.
Objectives We tried to research the relativity of the different phenotypes and the traditional Chinese medicine constitution classification of essential hypertensive patients from the viewpoint of the insulin resistance、LV hypertrophy、LV diastolic dysfunction and response to treatment.We also tried to find the most effective anti-hypertensive drug for hypertensive patients according to the traditional Chinese medicine constitution classification of essential hypertensive patients.
Subjects and methods A total of 99 never or at least three months un-treatment essential hypertensive patients from Jiannren Hospital were classified into two types, the syndrome of the Yin-Deficiency and Yang-Excess type (type A) and the syndrome of the Phlegm-Dampness abundant type (type B), according traditional Chinese medicine constitution classification and evaluated by recording home blood pressure during the study periods. LV mass and performance were measured by M-mode echocardiography and mitral flow in diastole did by pulsed-wave Doppler. Insulin and C-peptide were assessed for determination of insulin resistance. We also assessed the anti-hypertensive efficacy of valsartan between the two types.
Results Type A patients had lower insulin level (7.98 ±4.27 vs 11.39 ±9.54, P=0.033), less insulin resistance, smaller LV mass (187.78±56.82 vs 220.59±74.74, P=0.02), smaller end diastolic (28.99±10.66 vs 35.55±14.35, P=0.01) and end systolic volume (91.62±26.42 vs 104.21±31.79, P=0.03), lower systolic wall tension (2839.61±456.27 vs 3123.66±608.09, P=0.01), shorter E wave deceleration time (0.19±0.04 vs 0.20±0.04, P=0.04), less percentage of diastolic dysfunction, with good control and response rates to valsartan therapy than type B patients. On the other hand, with aging, the possibility of isolated systolic hypertension in type A group was noted more frequently than in type B group. Valsartan therapy for type A hypertensive patients is associated with profound and significant systolic BP (137.02 ± 14.62 mmHg vs 147.43 ± 12.63 mmHg, P=0.001) and diastolic BP (85.88 ± 8.99 mmHg vs 91.29 ± 10.43 mmHg, P=0.012) reduction at 4 weeks treatment.
Conclusions We concluded that according to the traditional Chinese medicine constitution classification, hypetensive patients can be divided into two groups. They have different insulin level, LV mass, hemodynamic pattens, and even have different control and response rates of valsartan therapy. Valsartan therapy for type A hypertensive patients is associated with significant BP reduction at 4 weeks treatment, with good control and response rates, and should therefore be preferred as first line antihypertensive drug in the groups. In contrast, Valsartan therapy for type B hypertensive patients has poor control and response rates and it will not be suggested.

目 錄
第一章 前　言 1
第二章 文獻探討 4
第一節 西方醫學對原發性高血壓的認識 4
一、西方醫學高血壓病之歷史背景 4
二、西方醫學高血壓病之病名定義 5
三、西方醫學高血壓病之流行病學 7
四、西方醫學高血壓病之臨床症狀 7
五、西方醫學高血壓的病因病機 8
(A)高血壓的病因　 9
(1) 遺傳因素　 9
(2) 体重因素　 9
(3) 營養因素　 10
(4) 吸煙　 11
(5) 精神和心理因素 11
(6) 葯物　 12
(7) 氣候　 12
(8) 年齡　 12
(9) 環境與職業 12
(10)其他 12
(B)高血壓的病機 12
(1) 鈉鹽過度攝取 12
(2) 腎素-血管緊張素-醛固酮系統活化學說 13
(3) 交感腎上腺素能系統功能亢進學說 15
(4) 細胞膜離子通道異常學說 15
(5) 血管的增生肥厚 17
(6) 血管內皮細胞衍生之舒張及收縮因子 18
(7) 胰島素抵抗 23
(8) 排鈉性胜 30
(9) 前列腺素 31
(10) Kinin 系統 31
(11) Vasopressin 31
(12) 免疫 32
六、西方醫學高血壓病診斷分型 32
七、西方醫學高血壓治療 34
第二節 傳統醫學對原發性高血壓的認識 36
一、傳統醫學高血壓病名定義 36
二、傳統醫學高血壓病之歷史背景 37
三、傳統醫學高血壓的病因病機 38
(A) 傳統醫學高血壓的病因 38
(B) 傳統醫學高血壓病機 39
四、傳統醫學高血壓病診斷分型 40
五、傳統醫學高血壓治療 42
第三節 中西結合對原發性高血壓之臨床研究進展 43
一、中西醫病因病機結合 44
二、中西醫診斷分型結合 47
三、中醫病因病機結合西醫診斷分型 48
四、中醫診斷分型結合西醫病因病機 48
(A) 高血壓病辨証分型與体液因素的關係 48
(1) 腎素一血管緊張素一醛固酮系統(RAAS)的關係 48
(2) 前列腺素E1(PGEl)、前列腺素F2α (PGF2α)、cAMP、cGMP、
p物質、血栓素B2 (TXB2)、血漿心鈉素(ANF)的關係49
(3) 性激素的關係 50
(4) 胰島素抵抗的關係 50
(5) endothelin、NO、CGRP的關係 50
(B) 高血壓病中醫辨証分型與血液、循環的關係 51
(1) 血液流變學的關係 51
(2) 血小板聚集功能的關係 51
(3) 紅細胞變形能力的關係 51
(4) 凝血及纖溶系統功能的關係 51
(5) 指甲微循環變化的關係 51
(6) 腦血流改變的關係 52
(7) 血脂水平的關係 52
(C) 高血壓病中醫辨証分型與心臟大血管形態的關係 52
(D) 高血壓病中醫辨証分型與動態血壓的關係 52
(E) 高血壓辨証分型與免疫的關係 53
(F) 高血壓辨証分型與自由基代謝的關係 53
(G) 高血壓病中醫辨証分型與人格特徵的研究 53
五、單味中藥之中西醫結合研究 53
六、西醫診斷分型結合中藥治療 56
七、中醫診斷分型結合西藥治療 56
第三章 材料與方法 57
一、研究設計 57
二、研究對象 57
三、研究方法 57
1.證型診斷之標準 57
2.治療流程 58
3.居家血壓自我監測 60
4.胰島素與C-peptide之測量及胰島素阻抗之計算 61
5.心臟超音波檢查 61
(a).M-mode心臟超音波測量 62
(b).血液動力學之測量 62
(c).左心室功能的評估 64
(d).杜卜勒(Doppler)心臟超音波測量 64
6.療效評估 65
四、統計分析 65
第四章 結果 66
第一節 原發性高血壓患者，中醫證型分類之研究 66
第二節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，前負荷、後負荷、左心室心肌收縮功能及血液動力學差異之研究 67
第三節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，左心室心肌重量及左心室肥厚結構之研究 69
第四節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，胰島素、C-peptide與胰島素阻抗之研究70
第五節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，左心室舒張功能之研究 80
第六節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型，其收縮壓與舒張壓特性之研究 82
第七節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，心電圖差異之研究 86
第八節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型，對Angiotension II blocker治療之療效評估及影響療效的因素之研究 87
第九節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，脈搏壓(pulse pressure)、平均動脈壓(mean artery pressure)、大血管硬化指標(large artery stiffness)、周圍血管阻力(peripheral artery
resistance)與年齡之研究 94
第十節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間， discrimination analysis之研究 97
第五章 討論 101
第一節 原發性高血壓患者，中醫證型分類之研究 101
第二節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，前負荷、後負荷、左心室心肌收縮功能及血液動力學差異之研究 105
第三節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，左心室心肌重量及左心室肥厚結構之研究107
第四節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，胰島素、C-peptide與胰島素阻抗之研究109
第五節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，左心室舒張功能之研究 113
第六節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型，其收縮壓與舒張壓特性之研究 116
第七節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，心電圖差異之研究 118
第八節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型，對Angiotension II blocker治療之療效評估及影響療效的因素之研究 120
第九節 原發性高血壓患者，陽亢型(陰虛陽亢型或肝火上亢型)和痰濕中阻型間，脈搏壓(pulse pressure)、平均動脈壓(mean artery pressure)、大血管硬化指標(large artery stiffness)、周圍血管阻力(peripheral artery
resistance)與年齡之研究 127
第六章 結論 135
參考文獻 136
英文摘要 167

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