臺灣博碩士論文加值系統

在本態性高血壓病程早期，可以觀察到交感神經活性提升的現象，也暗示自律神經失調可能在高血壓的致病機轉及病程進展扮演關鍵角色。過去研究指出，在高血壓患者中，過度興奮的交感神經活性會對器官功能造成負面影響，也與心血管系統併發症的發生有關。然而，目前關於患者用於高血壓控制的藥劑，如：血管收縮素接受器阻斷劑 (angiotensin II receptor antagonist, ARB) 或鈣離子通道阻斷劑 (calcium channel blocker, CCB) 對心血管系統自律神經功能的影響尚未有明確的結論。
在本試驗中，我們假設高血壓患者相較於健康受試者有較高的交感神經活性及較低的副交感神經活性，但使用高血壓藥物，包含ARB或CCB，以達到理想血壓控制的病患，相較於未使用高血壓藥物控制的病患，這種自律神經功能失衡的狀況會有所改善。我們收錄二十二位有原發性高血壓病史但未接受降血壓藥劑治療，十九位及十二位分別接受單獨ARB或CCB類藥物治療至少一年的高血壓病患，及三十九位健康成年人為受試者，以多頻道睡眠記錄儀 (polysomnography) 及連續血壓記錄儀同步收集每位受試者午睡期間的腦波、眼動、肌電、心電及血壓等生理訊號。根據記錄所得生理訊號，分析高血壓未治療，接受治療者，及健康受試者心率變異性及感壓反射的差異。藉由心率變異性的頻譜分析估算得到心臟副交感及交感神經的調控活性，分別表示為高頻功率 (HF) 及低高頻功率的比值 (LF/HF ratio) 或標準化低頻功率 (LF%)。自發性感壓反射以兩種方式評估: 1.動脈壓-心率轉換函數法。依所量取的頻率位置，此數值又分為低頻 (BrrLF) 和高頻 (BrrHF) 兩者。2. 根據自然發生，前後連續三跳以上的動脈壓和心率變化進行線性回歸。即血壓持續上升且心率持續下降，將超過三跳的動脈壓-心率資料組進行線性回歸可得一斜率 (BrrA)；反之，血壓持續下降且心率持續上升，超過三跳的動脈壓-心率資料組進行線性回歸可得一斜率 (BrrD)。以上四個參數(BrrLF, BrrHF, BrrA, BrrD) 均能反應感壓反射靈敏度。
分析結果發現，在午睡清醒期，高血壓未治療患者相較於健康受試者呈現較高的交感神經活性及較低的副交感神經活性。使用ARB治療的高血壓患者相較於健康受試者呈現較低的副交感神經活性，但兩組間的交感神經活性則沒有顯著差別。使用CCB治療的高血壓患者與健康受試者比較，在交感及副交感神經活性，都沒有顯著差異。在感壓反射方面，所有高血壓患者，無論是否接受降血壓藥劑治療，在四個感壓反射參數，包含BrrLF, BrrHF, BrrA及BrrD均較健康受試者低。
根據上述分析結果，我們可以推論，藉由使用ARB或CCB類藥物達到理想的血壓控制，可以同時調節高血壓患者的交感神經活性。然而，高血壓患者感壓反射降低的現象，則無法藉由使用ARB或CCB類藥物或是理想的血壓控制而達到改善。這也暗示了高血壓的病程進展，或是高血壓藥物本身，對心臟或是血管自律神經系統的影響可能是不一致的，兩者功能失調的可逆性亦不盡相同。

Background:
Enhanced sympathetic drive has been established as being associated with the early stage of essential hypertension, suggesting the autonomic dysregulation may be key to the disease's etiology and progression. Sympathetic predominance in hypertension is associated with deleterious effects on target organs and predicts the development of cardiovascular complications. The effects of antihypertensive agents on cardiovascular autonomic function remain controversial.
Methods:
In total, 53 patients with essential hypertension and 39 healthy control subjects were recruited into the present study. Among the patients with hypertension, 22 patients were unmedicated, 19 patients were being treated with an angiotensin II receptor antagonist (ARB), and 12 patients were being treated with a calcium channel blocker (CCB). Participants underwent polysomnography and noninvasive continuous arterial blood pressure recording simultaneously during nap sleep. The ECG and arterial blood pressure signal results were used for heart rate variability (HRV), and spontaneous baroreflex sensitivity (BRS) analysis. Spectral analysis of the HRV was performed in order to assess the cardiac parasympathetic modulation (high-frequency power, HF) and cardiac sympathetic modulation (normalized low-frequency power, LF% and LF/HF ratio) of the study subjects. Spontaneous BRS was estimated from (1) the magnitudes of arterial pressure and R-R interval transfer function across both the high frequency (BrrHF) and low frequency (BrrLF) ranges and (2) the slopes of the linear regression of the mean arterial pressure and R-R intervals pairs that both ascended (BrrA) and descended (BrrD) successively.
Results:
While awake, the unmedicated hypertensive subjects showed lower parasympathetic activity (HF) and higher sympathetic activities (LF/HF and LF%) than the controls. In contrast, the ARB group showed only lower HF power than the controls, but had similar sympathetic (LF/HF or LF%) activities. There was no significant difference in HF, LF/HF or LF% between the CCB and control groups. All hypertensive patients, with or without antihypertensive agents, showed lower BRS indices, BrrLF, BrrHF, BrrA, and BrrD than the controls during waking.
Conclusion:
Among hypertensive patients treated with either ARB or CCB, any increases in cardiac sympathetic activities were normalized; however the reduction in BRS associated with hypertension was not affected.

Table of Contents

Table of Contents i
List of Tables iii
List of Figures iv
中文摘要 v
Abstract vii
Chapter 1 Introduction 1
Chapter 2 Literature Review 3
2.1 Hyperadrenergic state in essential hypertension 3
2.2 Sympathetic activation as determinant of 24-hr blood pressure profile and blood pressure variability 4
2.3 Mechanism responsible for adrenergic overdrive 5
2.4 Chronic baroreceptor resetting with hypertension 6
Chapter 3 Study Purpose 7
Chapter 4 Methods 8
4.1 Participants 8
4.2 Procedure 9
4.3 Measurements 10
4.3.1 Polysomnographic recording 10
4.3.2 Continuous blood pressure recording 10
4.4 Data acquisition 10
4.4.1 Sleep analysis 10
4.4.2 Heart rate variability and arterial pressure variability 11
4.4.3 Baroreflex sensitivity 12
4.5 Statistical analysis 13
Chapter 5 Results 14
5.1 Characteristics of study subjects 14
5.2 Comparison of the heart rate variability indices across the four groups 14
5.3 Comparisons of arterial pressure variability and spontaneous baroreflex sensitivity measures across the four groups 15
5.4 Sensitivity analysis with Losartan treatment group 16
5.4.1 Characteristics of analysis subjects 16
5.4.2 Comparison of the heart rate variability indices across the three groups 17
5.4.3 Comparison of arterial pressure variability and spontaneous baroreflex measures across the three groups 17
Chapter 6 Discussion 19
6.1 Arterial pressure variability in chronic hypertension with or without treatment 19
6.2 Alternation of heart rate variability and baroreflex sensitivity in chronic hypertension with or without treatment: discrepancy in irreversibility 20
6.3 Differential effects of angiotensin II receptor antagonists and calcium channel blockers on autonomic modulation in chronic hypertension 21
6.4 The rationale of nap sleep recordings 23
6.5 Limitations 24
6.6 Conclusions 25
Chapter 7 References 26

List of Tables
Table 1. Baseline characteristics of the healthy control and hypertensive patients 36
Table 2. Comparisons of heart rate variability indices between the healthy control and hypertensive patients 37
Table 3. Comparisons of arterial pressure variability and spontaneous baroreflex sensitivity measures between the healthy control and hypertensive patients 39
Table 4. Baseline characteristics of the healthy control and hypertensive patients (unmedicated and Losartan treated subgroup) 41
Table 5. Comparisons of heart rate variability indices between the healthy control and hypertensive patients (unmedicated and Losartan treated subgroup)42
Table 6. Comparisons of arterial pressure variability and spontaneous baroreflex sensitivity measures between the healthy control and hypertensive patients (unmedicated and Losartan treated subgroup)43

List of Figures
Figure 1. Comparisons of heart rate variability indices between the healthy control and hypertensive patients according to different sleep stages 45
Figure 2. Comparisons of arterial pressure variability and spontaneous baroreflex sensitivity measures between the healthy control and hypertensive patients according to different sleep stages..47

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