動脈壓力波之諧頻分析可靠度驗證與其臨床應用──以茶為例

Abstract

動脈壓力波分析相關研究已經發展了數十年，也為此開發許多動脈壓力波量測儀器。然而，到目前為止缺乏一系列完整評估的系統和標準的流程，對動脈壓力波量測儀器進行諧頻分析之驗證，包括評估儀器本身的可靠度、同一操作者的量測的再現性，不同操作者的一致性等。因此，本論文有三個主要的目標：第一，我們目標建立模擬動脈壓力波的仿體系統，去評估動脈壓力波量測儀本身的可靠度；第二，我們目標在於建立一標準的臨床程序，去評估動脈壓力波量測儀的操作者內、操作間的可靠度。我們用動脈壓力波分析儀TD01C(米安科技，台灣)做為一個範例，來驗證我們前兩個目標的可行性；第三，我們執行一喝茶效應的臨床測試，藉此觀察動脈壓力波量測與諧頻分析，是否能有效的用來監測血循環狀態的變化，並且用來評估功能性食品或保健食品的功效。 在第一階段的研究，我們會建立一模擬動脈壓力波的仿體系統，用來製造週期性的壓力波，並且用DP103壓力感測器(Validyne，加州，美國)去驗證週期性輸出的可靠度。接著，我們會用此模擬動脈壓力波的仿體系統系統，來評估TD01C重複量測的再現性與多台儀器間的一致性。我們會用諧頻分析、變異係數、組內相關係數(ICC)、以及布蘭德-奧特曼圖(Bland-Altman plot)來評定TD01C的可靠程度。實驗的結果證明：1. 模擬動脈壓力波的仿體是一個可靠的評估系統用來驗證動脈壓力波量測儀本身的可靠度(ICC>0.95,p<0.001)。2.證明TD01C本身有可靠的再現性((ICCs of test–re-test reliability>0.95, p<0.001; CVs all<3%).) 3.實驗結果確認了用模擬動脈壓力波的仿體系統評估動脈壓力波量測儀本身的可靠度是一個可執行、可操作的方法。 實驗的第二步，我們使用TD01C對健康的受測者進行臨床測試，評估以TD01C量測橈動脈動脈壓力波時，同一操作者重複量測的再現性或不同操作者間量測的一致性。我們用諧頻分析方法來定量，探索連續量測所得動脈壓力波之諧頻的可靠度。組內相關係數和Bland-Altman圖被用來定量、驗證動脈壓力波量測儀的穩定程度。22個受測者(平均年齡45±14 歲; 14男和8女) 被招募進行可靠度測試──包含操作者內與操作者間量測。實驗的結果顯示：TD01C在同一操作者的重複量測實驗上有很好的再現性(ICCs>0.9, p<0.001)；TD01C在不同操作者的連續量測中很好的一致性(ICCs 介於 0.83-0.96, p<0.001)。在Bland-Altman圖中，超過90% 諧頻，連續兩次量測的差值落在兩倍標準差範圍內。總結的來說，用TD01C來量測動脈壓力波是一可操作且可靠的方法，適合在臨床試驗中用來描繪動脈系統的狀態特徵。 第三步，本研究進行一項臨床測試來觀測飲茶對血循環的影響。我們用TD01C來量測橈動脈的動脈壓力波，並且用血壓計HEM-6051 (Omron, Japan)來量測血壓。我們接著用諧頻分析來評估動脈系統狀態的改變。研究結果顯示：飲用立頓紅茶、三峽蜜香紅茶、三峽碧螺春綠茶，都能增強動脈壓力波中高頻的成分(從第6到第11諧頻) 我們推論茶能夠增進腦部血循環，並因此推論茶葉具有保護神經的效果。 總結來說，TD01C系統經過仿體與臨床驗證其可靠度後，其儀器可靠度達到有臨床詮釋效力的標準。再加上飲茶實驗透過TD01C能夠觀察到動脈系統不同的狀態特徵，這顯示TD01C在心血管系統的臨床研究與應用上有很大的潛力，值得進行更多後續的研究。

Pulse wave analysis (PWM) has been studied for many decades and many pressure measuring instruments were developed for this purpose. However, there was no complete assessment system and standard protocol to quantify the intrinsic reliability, intra-observer repeatability, and inter-observer reproducibility for clinical evaluation of a pressure measuring instrument. Therefore, there are three main purposes of this study. First, we aimed to assess intrinsic reliabilities of devices for pulse wave measurement using artificial pulse generator. Second, this study was aimed to establish a standard protocol for clinical test and to quantitatively assess the reliability of pulse wave analysis system, including intra-observer reliability, and inter-observer reliability. We used Pulse wave analyzer TD01C (MII-ANN Technology, Taiwan) as an example to validate the feasibility of previous two purposes. Third, we performed a clinical test of tea consumption to demonstrate pulse wave analysis could be useful in monitoring the circulation and to evaluate the effect of functional food or health product. In the first step of the study, we build up an artificial pulse generator system to create a periodic pulse wave and DP103pressure transducer (Validyne, CA, USA) was used to test the stability of the periodic output. We then used the pulse generator system for evaluating the test–re-test and inter-device reliability of the TD01C system. We used harmonic analysis (HA), the coefficient of variation (CV), intra-class correlation coefficient (ICC) and Bland-Altman plot to determine the degree of reliability of the TD01C system. The artificial pulse generator system was proved stable to evaluate intrinsic reliabilities of devices for PWM (ICCs>0.95, p<0.001). TD01C was proved reliable for repeated measurements (ICCs of test–re-test reliability>0.95, p<0.001; CVs all<3%). The report confirmed the feasibility of intrinsic reliability assessment of devices for PWM using an artificial pulse generator system. The second step of the study, we used the TD01C system to perform a clinical test on healthy subjects and tested TD01C’s intra-observer and inter-observer reliability in PWM of the radial pulse wave. We conducted assessments using HA and investigated the stabilities of harmonics in successive measurements. ICC and Bland-Altman plot was used to verify the level of the stabilities. Twenty-two subjects (mean age 45±14 years; 14 males and 8 females) were enrolled for both the reliability assessments of intra-observer and of inter-observer. The report presented excellent repeatability (Intraclass correlation coefficients, ICCs>0.9, p<0.001) for intra-observer assessment and high reproducibility (ICCs range from 0.83-0.96, p<0.001) for inter-observer assessment. In the Bland-Altman plots, more than 90% of harmonics fell within two standard deviations of the mean difference. Consequently, PWM using TD01C system is a feasible and reliable method to assess hemodynamic characteristic in a clinical test. Third, the study performed a clinical test to investigate the effect of tea consumption on brain circulation. The radial pulse wave was measured by the TD01C system and blood pressure was measured with blood pressure monitor HEM-6051 (Omron, Japan). We used HA to evaluated circulation change. The report confirmed that consumption of Lipton black tea, Sanxia black tea, and Sanxia green tea all increased higher harmonic components (from sixth to tenth harmonic components of radial blood pulse). We conclude that tea could increase cerebral blood flow and thus the possible mechanism of tea-mediated neuroprotective effect is not only by the neuroprotective compounds of tea but also by increasing the brain perfusion. In summary, the TD01C measuring system, which was validated by the phantom test and clinical test, reached the reliability for clinical interpretation. In addition to its ability to identify the different characteristics for different status of the arterial system, there is great potential to apply the TD01C system on the cardiovascular research and is worthy to carry out more investigation.