Ondocin Philip T, Narsipur Sriram S
Division of Nephrology, Department of Medicine, State University of New York Upstate Medical University, Syracuse, New York, USA.
Nephrology (Carlton). 2006 Dec;11(6):497-501. doi: 10.1111/j.1440-1797.2006.00680.x.
Cardiovascular disease mortality among patients with end stage renal disease (ESRD) exceeds that which is predicted by traditional risk factors. Sudden death accounts for up to 15-38% of patients with ESRD found dead at home. Heart rate variability (HRV) is a reliable measure of autonomic modulation and has a very strong predictive value for ventricular arrhythmias and sudden death. A lower HRV is associated with increased risk. Modifying autonomic tone pharmacologically reduces death from dysrhythmia in the general population but has not been studied in ESRD.
We examined the effect of ramipril, an angiotensin converting enzyme inhibitor (ACEI) known in the general population to increase HRV, on cardiac function and heart rate variability in patients with renal failure. Eligible subjects on haemodialysis underwent a 2-week washout period free of ACEI or beta blockers, during which time hypertension was treated with amlodipine, which has been shown not to affect HRV. Haemodynamic and HRV measurements were obtained at baseline and after subjects were treated for 4 weeks with an ACEI.
Haemodynamics did not differ at 0 and 4 weeks. Baseline HRV values were markedly below those found in the general population, indicating pronounced predominance of sympathetic tone over vagal tone. Actual worsening of HRV with ACEI treatment was evident in several major time domains. The time domain SDNN (the standard deviation of all normal RR intervals) fell from 42.0 +/- 24.8 ms to 20.1 +/- 16.1 ms (P = 0.004) and the triangulation index fell from 178.0 +/- 94.0 to 115 +/- 59.2 (P = 0.01). A trend toward reduced HRV was seen in several other time domains.
These findings suggest that, unlike the general population, treatment of ESRD patients with an angiotensin converting enzyme inhibitor may cause a deleterious shift toward increased cardiac sympathetic nervous system tone.
终末期肾病（ESRD）患者的心血管疾病死亡率超过了传统危险因素所预测的水平。猝死在高达15% - 38%的在家中死亡的ESRD患者中占比很高。心率变异性（HRV）是自主神经调节的可靠指标，对室性心律失常和猝死具有很强的预测价值。较低的HRV与风险增加相关。在普通人群中，通过药物调节自主神经张力可降低心律失常导致的死亡，但尚未在ESRD患者中进行研究。
我们研究了雷米普利（一种在普通人群中已知可增加HRV的血管紧张素转换酶抑制剂（ACEI））对肾衰竭患者心脏功能和心率变异性的影响。符合条件的接受血液透析的受试者经历了为期2周的洗脱期，在此期间停用ACEI或β受体阻滞剂，在此期间使用氨氯地平治疗高血压，氨氯地平已被证明不影响HRV。在基线时以及受试者接受ACEI治疗4周后进行血流动力学和HRV测量。
0周和4周时血流动力学无差异。基线HRV值明显低于普通人群，表明交感神经张力明显高于迷走神经张力。在几个主要时域中，ACEI治疗后HRV实际恶化明显。时域中的SDNN（所有正常RR间期的标准差）从42.0±24.8毫秒降至20.1±16.1毫秒（P = 0.004），三角指数从178.0±94.0降至115±59.2（P = 0.01）。在其他几个时域中也观察到HRV降低的趋势。
这些发现表明，与普通人群不同，用血管紧张素转换酶抑制剂治疗ESRD患者可能会导致心脏交感神经系统张力增加的有害转变。
