心血管危險指標於輕度高血壓患者及 第二型糖尿病患者之系列研究

Serial Studies of Cardiovascular Risk Indicators Among Mild Hypertensives and Type 2 Diabetics

王美業(Mei-Yeh Wang)

指導教授 ： 蔡佩珊

臺北醫學大學/醫學院/醫學科學研究所/博士(2010年)

https://doi.org/10.6831/TMU.2010.00160

摘要

過去研究已提出動脈硬化、清晨血壓竄升值過高以及憂鬱症狀與心血管疾病的發生或是惡化有關。動脈硬化指標中包含動態動脈硬化指標與主動脈硬化指數均有研究顯示可預測心血管疾病以及心血管標的器官損傷。然而動態動脈硬化指標是否真的反應出動脈硬化現象，亦或實際上反應其他操控因子對動脈枝的影響有待研究證實。而在正常血壓之糖尿病患者中，其心血管疾病的風險性是否可藉由主動脈硬化指數的提高而偵測出，其主動脈硬化指數是否已經較輕度高血壓患者高，以及主動脈硬化指數是否與其它心血管疾病風險指標有關未曾被探討。再者，過去研究也指出於高血壓患者中，清晨血壓竄升值過高是腦血管意外事件及心血管標的器官損傷的預測因子。但在未治療之輕度高血壓患者中，清晨血壓竄升這個指標本身的穩定性尚未檢驗。此外，慢性病人所合併之憂鬱症狀本身即可能增加心血管疾病的風險性，而糖尿病患者常見合併有憂鬱症狀，過去研究指出憂鬱症狀不但會影響糖尿病患者的血糖控制，且合併有憂鬱症狀之糖尿病患者其冠狀動脈疾病死亡率比單獨有糖尿病之患者高。然而於第二型糖尿病患者中，非藥物治療措施於降低憂鬱症狀後對增加患者血糖控制之成效，未見有系統性的被檢視。
本論文共包含四個系列研究，探討動態動脈硬化指標、主動脈硬化指數、清晨血壓竄升值、以及憂鬱症狀等心血管危險指標，在輕度高血壓患者及第二型糖尿病患者之病生理機轉、適用性與穩定性等主題；以及針對憂鬱症之非藥物治療對第二型糖尿病患者血糖控制的成效。子研究一主要探討壓力反射器敏感度對動態動脈硬化指標之操控。研究結果發現動態動脈硬化指標與脈波流速無顯著相關，但和靜止時的壓力反射器敏感度及壓力測試過程時的壓力反射器敏感度呈現顯著負相關。在控制干擾變項包含年齡、性別、二十四小時平均血壓及夜間血壓降幅後，靜態壓力反射器敏感度仍與動態動脈硬化指標呈顯著負相關。本研究結果顯示在有心血管疾病危險的個案中，動態動脈硬化指標主要受心血管神經系統的操控，動態動脈硬化指標與心血管疾病的關連可能與壓力反射器敏感度的降低有關。
子研究二主要比較正常血壓之第二型糖尿病患者與輕度高血壓患者間之主動脈硬化指數。在控制年齡及身高等變項後，兩個族群的主動脈硬化指數值無顯著差異，但糖尿病患者比高血壓患者有較少的夜間血壓降幅值。此外在糖尿病患者中，主動脈硬化指數與夜間血壓降幅值及糖化血色素值均無顯著相關。本研究結果顯示於正常血壓之第二型糖尿病患者族群中，以主動脈硬化指數來偵測心血管疾病危險性的臨床應用可能有限。
子研究三主要探討在新近被診斷為輕度高血壓且從未接受治療的患者中，清晨血壓竄升值的穩定性以及與血壓應激反應的關係。本研究總共測得三次的動態血壓測量數值，並利用Bland-Altman分析方式檢驗任兩次測量間的一致性。分析結果顯示，任兩次測量值的一致性區間均超過臨床可接受範圍，且重複測量間的變異係數大。此外，清晨血壓竄升值與血壓應激反應值無顯著相關。清晨血壓竄升值主要由夜間血壓平均值而非清晨血壓平均值決定，夜間血壓有下降者也比夜間血壓無下降者有較高之清晨血壓竄升值。本研究結果顯示，清晨血壓竄升值於輕度高血壓患者中並不是穩定的測量變項，而且推測清晨血壓竄升之病理起源可能與夜間血壓下降有關。
子研究四主要探討於第二型糖尿病患者中，採用非藥物治療措施降低憂鬱症狀與血糖控制的成效。本研究採用系統性文獻回顧的方式進行，並以統計上之效應值評定治療成效，共計有三篇臨床試驗研究被收錄。結果顯示，非藥物治療雖可有效降低憂鬱症狀，但在血糖控制變項上的統計效應值偏低。本研究結果顯示只治療憂鬱症狀之非藥物措施對增加第二型糖尿病患者血糖控制之效果有限。
總結，本系列研究結果有助於瞭解在輕度高血壓患者及第二型糖尿病患者中動態動脈硬化指標之調控機轉，主動脈硬化指數於預測第二型糖尿病患者心血管疾病風險之適用性，以及清晨血壓竄升值在輕度高血壓患者的穩定性。此外，也提出實證證明作為日後於合併憂鬱症之第二型糖尿病患者中，增進其血糖控制的非藥物治療措施參考。

關鍵字

心血管危險指標 ； 高血壓 ； 糖尿病

並列摘要

A growing body of evidence has linked arterial stiffness, exaggerated morning blood pressure surge (MBPS), and comorbid depression to a higher incidence of cardiovascular disease or poor cardiovascular prognosis. The role of indices of arterial stiffness, including the ambulatory arterial stiffness index (AASI) and the aortic augmentation index (AI) in predicting adverse cardiovascular events and target organ damage has been supported in previous studies. However, the question of whether AASI is a measure of arterial stiffness or reflects the influence of other origins on the arterial tree remains to be determined. The question of whether normotensive type 2 diabetic subjects may have a greater cardiovascular risk determined by AI than mildly hypertensive subjects also remains unanswered. The association between AI and other cardiovascular risk indicators in normotensive type 2 diabetic subjects has yet to be determined. Excessive MBPS has been demonstrated to be a predictor of cerebrovascular events and target organ damage in subjects with essential hypertension. However, the reproducibility of MBPS in untreated mildly hypertensive subjects has not been investigated. Furthermore, comorbid depression is associated with poor cardiovascular prognosis. Depression is often seen in diabetic patients and may contribute to poor control of blood sugar in diabetic patients. Individuals with diabetes and depression also have a significantly higher coronary heart disease mortality rate than individuals with diabetes alone. Yet, the efficacy of non-pharmacological treatments of depression in improving glycemic control in type 2 diabetic subjects has not been systematically examined.
This dissertation includes four studies. The first study focused on the influence of baroreflex sensitivity (BRS) on AASI in subjects with cardiovascular risk. The results demonstrated that AASI was not correlated to pulse wave velocity (PWV) but was significantly and inversely correlated to resting BRS. Adjusting for possible confounders including age, gender, 24-hour mean arterial pressure, and nocturnal blood pressure decline, BRS independently predicted AASI. Our finding of the influence of BRS on AASI suggests that AASI may be mainly affected by cardiovascular neural regulation in subjects with cardiovascular risk. Decreased BRS may at least, in part, explain the prognostic role of AASI in predicting cardiovascular risk.
The second study focused on the comparison of AI in type 2 diabetic subjects with normal BP and mildly hypertensive subjects. After adjusting for age and body height, there was no difference in AI between groups. On the other hand, the diabetic group exhibited a significantly blunted nocturnal BP decline compared to the mildly hypertensive group. In the diabetic group, AI was correlated to neither nocturnal BP decline nor HbA1C. Results from our study raise the question that AI may not be a useful maker for CV risk in normotensive type 2 diabetic patients.
The third study focused on the reproducibility of MBPS in subjects who were newly diagnosed with mild hypertension and had never been treated with anti-hypertensive medications. The association between MBPS and BP reactivity to mental stress was also investigated. Ambulatory blood pressure monitoring (ABPM) was carried out three 24-hour periods. The results demonstrated that the limits of agreement between any one pair of measurements determined by the Bland-Altman analysis were large and clinically unacceptable. The within-subjects coefficient of variation (CV) of ABPM measurements was also large. In addition, MBPS was not related to BP reactivity to mental stress. The magnitude of the MBPS was largely determined by the nighttime reduction in BP rather than the morning elevation in BP. Subjects with a nocturnal BP dipping profile also had a greater magnitude of MBPS than subjects without a nocturnal BP dipping profile did. Our results thus suggest that MBPS is not a stable measure over time in untreated mildly hypertensive patients. Moreover, MBPS and nocturnal dipping may be two concepts of the same origin.
The fourth study systemically assessed the efficacy of non-pharmacological treatment of depression on glycemic control in individuals with type 2 diabetes. A total of three randomized controlled clinical trials were included in this systematic review. Findings from this review demonstrated that non-pharmacological treatments of depression reduced depressive symptoms in diabetic patients. However, the treatment effect sizes for glycemic control in the collaborative care programs were small. The available evidence demonstrated that non-pharmacological treatment of depression had limited an effect on glycemic control in individuals with type 2 diabetes.
In conclusion, results from these studies may add knowledge to the possible pathophysiological mechanisms of AASI in individuals with mild hypertension or type 2 diabetes, the validity of AI as a marker of cardiovascular risk in individuals with type 2 diabetes, and the reproducibility of MBPS in individuals with mild hypertension. In type 2 diabetic patients with depression, results from our study also provide evidence-based recommendation for using non-pharmacological treatment in glycemic control in future studies.

並列關鍵字

Cardiovascular risk indicator ； Hypertension ； Type 2 Diabetes

參考文獻

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