慢性腎臟病患心臟超音波及心率變異之研究

Echocardiography and Heart Rate Variability in Patients with Chronic Kidney Disease

陳柏志(Po-Chih Chen)

指導教授 ： 黃友利

高雄醫學大學/健康科學院/醫學檢驗生物技術學系博士班/博士(2018年)

摘要

中文摘要
慢性腎臟疾病(chronic kidney disease, CKD)發病率和死亡率增加是全球公共衛生的重要議題，心血管疾病是慢性腎臟病患者發病和死亡的主要原因。在末期腎病中越來越多的證據顯示心血管疾病死亡與心臟超音波的經二尖瓣E波速度與舒張早期二尖瓣速度的比值 (E/Ea)有相關，但在第二型糖尿病(diabetes mellitus, DM)和E/Ea的組合是否可以預測慢性腎臟病患者的不良心血管疾病預後很少被研究。另外第2型糖尿病是全球慢性腎臟疾病的主要原因之一，目前很少有研究探討慢性腎臟病病人有糖尿病與非糖尿病的心臟超音波比較，並用超音波探討糖尿病及心臟超音波預後。所以我們設計了兩個實驗想了解慢性腎臟病患者與心臟檢查之間的關係。
研究-1包括356例慢性腎臟病 3-5期患者進行心臟超音波檢查。所有患者根據有無糖尿病和E /Ea ≤或>9的存在分為四組。平均觀察期為25個月，有58例心血管事件發生。糖尿病和E / Ea > 9(與非糖尿病和E / Ea ≤ 9的組合比較)的組合與未調整模型中的心血管事件相關(危險比, 6.990; 95％信賴區間, 2.753-17.744; p < 0.001)，多變量調整模型(危險比, 3.037; 95％信賴區間, 2.088-7.177; p = 0.025)。在沒有糖尿病的患者中E / Ea比(p = 0.033)改善了心血管事件的預測( p = 0.001)。而在有糖尿病患者，E / Ea比值(p = 0.018)、左心房直徑(p = 0.016)和左心室質量指數(p = 0.001)改善了心血管事件的預測。合併有糖尿病、左心室舒張功能異常在慢性腎臟病 3-5期患者與心血管事件發生相關。評估有無糖尿病和E/Ea比率有助於識別產生不良心血管事件的高風險患者。
研究-2目的是調查尿酸在非糖尿病患者的血液透析患者在透析前後心率變異性變化(Δheart rate variability, ΔHRV)中的作用。96名非糖尿病且血液透析患者納入本次研究。ΔHRV的計算為血液透析後減去洗腎前心率變異性的變化。血中尿酸> 7 mg/dL的患者與尿酸 ≤ 7 mg/dL的患者相比，△高頻率% (p = 0.027)較低。尿酸與血液透析的非糖尿病患者的△高頻率％(r = -0.247，p = 0.015)和△低頻率/高頻率(r = -0.236，p = 0.021)呈負相關。此外在對人口、臨床、生物化學檢查和藥物調整後的多變量分析中，血中尿酸與△高頻率％(每1 mg/dL, 非標準化係數β= -2.892; 95%信賴區間, -5.066 to -0.717; p = 0.010)及△低頻率/高頻率(每1 mg/dL, 非標準化係數β= -0.165; 95%信賴區間, -0.291 to -0.038; p = 0.011)呈現獨立相關。高尿酸血症在非糖尿病患者的血液透析後導致較低的△高頻率％和低頻率/高頻率增加，反映了高尿酸血症非糖尿病血液透析患者的交感神經-迷走神經平衡受損狀態。
綜合以上研究指出評估腎臟病人有無糖尿病和E / Ea有助於識別產生不良心血管事件的高風險產生，降低腎臟病人血中尿酸可能會改善非糖尿病血液透析患者的心率變異性。

關鍵字

慢性腎臟病 ； 心臟超音波 ； 心率變異 ； 糖尿病 ； 經二尖瓣E波速度 ； 舒張早期二尖瓣速度 ； 心血管疾病 ； 血液透析 ； 尿酸

並列摘要

英文摘要
Increasing incidence and mortality of chronic kidney disease (CKD) is an important issue in global public health. Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD. There is increasing evidence in end-stage renal disease that mortality from cardiovascular disease is related to the E / Ea ratio, There is increasing evidence in end-stage renal disease that mortality from cardiovascular disease is related to the E/Ea ratio (ratio of transmitral E wave velocity to early diastole mitral velocity). In addition, type 2 diabetes is one of the leading causes of CKD in the world. At present, few studies have investigated the comparison of diabetic and non-diabetic echocardiography in patients with CKD, and used ultrasound to investigate the prognosis of diabetes and cardiac ultrasound. We want to know about the relationship between CKD patients with cardiac examination.
We designed two experiments. Study-1 included 356 CKD stage 3–5 patients underwent echocardiography. All patients were classified into four groups based on the presence of diabetes mellitus (DM) and E/Ea ≤ or > 9. There were 58 CV events during the mean observation period of 25.0 months. A combination of the presence of DM and E/Ea > 9 (vs. a combination of non-DM and E/Ea ≤ 9) was associated with CV events in unadjusted model (hazard ratio(HR), 6.990; 95% confidence interval, 2.753–17.744; p < 0.001), and in a multivariate adjusted model (HR, 3.037; 95% CI, 2.088–7.177; p = 0.025). In the patients without DM, the E/Ea ratio (p = 0.033) improved the prediction of CV events, compared to the E/ Ea ratio (p = 0.018), left atrial diameter (p = 0.016) and left ventricular mass index (p = 0.001) in the patients with DM. The combination of DM and left ventricular diastolic dysfunction was associated with CV events in patients with CKD stage 3–5. Assessments of DM status and E/Ea ratio may facilitate identifying high-risk patient population of unfavorable CV outcomes.
Study-2 was to investigate the role of Uric Acid (UA) in HRV changes before and after Hemodialysis (HD) in non-diabetic patients. Ninety-six nondiabetic patients under maintenance HD were enrolled. HRV was examined to assess changes before and after HD. A change in HRV (ΔHRV) was calculated as post-HD HRV minus pre-HD HRV. Compared to the patients with a UA level ≦ 7 mg/dL, those with a UA level > 7 mg/dL had lower Δhigh frequency (HF)% (p = 0.027). UA was negatively associated with ΔHF% (r = -0.247, p = 0.015) and Δlow frequency (LF)/ HF (r = -0.236, p = 0.021) in the non-diabetic patients undergoing HD. Furthermore, in multivariate analysis after adjustments for demographic, clinical, and biochemical characteristics and medications, UA was independently associated with ΔHF% (per 1 mg/dL, unstandardized coefficient β = -2.892; 95% CI, -5.066 to -0.717; p = 0.010) and ΔLF/HF (per 1 mg/dL, unstandardized coefficient β = -0.165; 95% CI, -0.291 to -0.038; p = 0.011). Hyperuricemia contributed to lesser HF% and LF/HF increase after HD in the non-diabetic patients, reflecting a state of impaired sympatho-vagal equilibrium in non-diabetic HD patients with hyperuricemia. In Summary two studies assessments of DM status and E/Ea ratio may facilitate identifying high-risk patient population of unfavorable CV outcomes, and lowering UA levels may have the potential to improve increased HRV in non-diabetic HD patients.

並列關鍵字

chronic kidney disease ； CKD ； echocardiography ； heart rate variability ； diabetes mellitus ； transmitral E wave velocity ； early diastole mitral velocity ； cardiovascular event ； hemodialysis ； uric acid

參考文獻

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