血液透析患者心脏自主神经功能障碍的影响因素分析

Influencing factors of cardiac autonomic dysfunction in hemodialysis patients

目的通过记录含透析过程总时长达48 h的长时程心率变异性(heart rate variability,HRV)并进行相关分析,探讨维持性血液透析(maintenance hemodialysis,MHD)患者心脏自主神经功能障碍的影响因素。方法本研究为单中心横断面研究,入选2021年10月1日至2022年12月31日在北京大学人民医院血液透析中心行MHD的患者,排除快速型心律失常、植入起搏器及动态心电图记录时长不足48 h的患者。动态心电图于平卧位休息5 min后在血液透析开始时记录,48 h后结束。收集患者的人口学资料、并发症、实验室资料、透析相关数据及HRV数据。使用多因素线性回归模型分析HRV的影响因素。结果共110例患者纳入分析,女性37例(33.6%),年龄(57.8±14.8)岁,36例(32.7%)患有糖尿病,中位透析龄73.00(27.75,130.25)个月,血磷(1.6±0.4)mmol/L,ln[N端B型钠尿肽前体(N⁃terminal pro B⁃type natriuretic peptide,NT⁃proBNP,ng/L)]8.4±1.2。全部正常窦性R⁃R间期的标准差(standard deviation of all normal R⁃R interval,SDNN)为(90.6±27.9)ms,相邻的R⁃R间期差值的均方根(root mean square of successive differences in R⁃R interval,RMSSD)对数(ln[RMSSD(ms)])为3.2±0.8,低频对数(ln[低频(ms^(2))])为3.4±1.3,高频对数(ln[高频(ms^(2))])为3.1±1.4,ln[低频/高频比]为0.28±0.64。校正年龄、冠心病、糖尿病、血红蛋白、血磷、25⁃羟基维生素D(25⁃OH⁃D)后,血钠(β=2.042,95%CI 0.021~4.064,P=0.048)和ln[NT⁃proBNP(ng/L)](β=-7.027,95%CI-12.247~-1.808,P=0.009)是SDNN的独立相关因素(调整后R2=0.218)。在以ln[低频(ms^(2))]为因变量的单因素线性回归分析中,糖尿病与MHD患者ln[低频(ms^(2))]具有相关性(β=-0.659,95%CI-1.171~-0.146,P=0.012),但在多因素模型中未观察到糖尿病与ln[低频(ms^(2))]的相关性有统计学意义。校正糖尿病、冠心病、透析龄、血红蛋白、血磷、血清白蛋白、透析前后收缩压、透析前舒张压后,年龄(岁)增长(β=-0.011,95%CI-0.019~-0.003,P=0.007)、ln[NT⁃proBNP(ng/L)]升高(β=-0.151,95%CI-0.253~-0.048,P=0.004)与ln[低频/高频比]下降独立相关。在分别以ln[高频(ms^(2))]和ln[RMSSD(ms)]为因变量的多因素线性回归模型中,校正了相关因素后,血磷(mmol/L)升高是ln[RMSSD(ms)]下降(β=-0.421,95%CI-0.777~-0.065,P=0.021)和ln[高频(ms^(2))]下降(β=-0.752,95%CI-1.325~-0.180,P=0.010)的独立相关因素。结论血磷升高是MHD患者副交感神经功能减退的独立相关因素;NT⁃proBNP升高与SDNN、低频/高频比下降相关,提示在MHD患者中需要重视血磷及容量的管理。高龄MHD患者自主神经功能障碍严重,在长期的血液透析中需要引起关注。

Objective To investigate the influencing factors of cardiac autonomic dysfunction in maintenance hemodialysis(MHD)patients by recording 48 h heart rate variability.Methods It was a single-center cross-sectional study.MHD patients at the Hemodialysis Center of Peking University People's Hospital between October 1,2021 and December 31,2022 were enrolled in the study.These patients initiated hemodialysis for more than three months and were older than 18 years old,and patients with tachyarrhythmia,implanted cardiac pacemaker and the recording time less than 48 h were excluded.Demographic data,comorbidity,laboratory data,hemodialysis session data and heart rate variability were collected.Multivariate linear regression model was used to analyze the influencing factors for cardiac autonomic dysfunction in MHD patients.Results A total of 110 patients were enrolled in the study,including 37 females(33.6%)and 36 diabetic patients(32.7%).The age of the patients was(57.8±14.8)years old,and the median dialysis vintage was 73.00(27.75±130.25)months.At baseline,the serum phosphate level was(1.6±0.4)mmol/L,and the N-terminal pro B-type natriuretic peptide(NT-proBNP)after ln transformed{ln[NT⁃proBNP(ng/L)]}was 8.4±1.2.The standard deviation of all normal R-R interval(SDNN)was(90.6±27.9)ms,ln[root mean square of successive differences in R-R interval(RMSSD,ms)]3.2±0.8,ln[low frequency(ms^(2))]3.4±1.3,ln[high frequency(ms^(2))]3.1±1.4,and ln[low frequency/high frequency ratio]0.28±0.64.After adjusting the age,coronary heart disease,diabetes,hemoglobin,serum phosphate and 25-hydroxy-vitamin D,serum natrium(β=2.042,95%CI 0.021–4.064,P=0.048)and ln[NT-proBNP(ng/L)](β=-7.027,95%CI-12.247–-1.808,P=0.009)were independently correlated with SDNN(adjusted R2=0.218).Univariate linear regression model showed that diabetes was correlated with ln[low frequency(ms^(2))]of MHD patients(β=-0.659,95%CI-1.171–-0.146,P=0.012),but in the multivariate linear regression model,significant correlation between diabetes and low frequency was not found.After adjusting the diabetes,coronary heart disease,dialysis vintage,hemoglobin,serum phosphate,serum albumin,pre-dialysis systolic blood pressure,post-dialysis systolic blood pressure,pre-dialysis diastolic blood pressure,increasing age(β=-0.011,95%CI-0.019–-0.003,P=0.007)and ln[NT-proBNP(ng/L)](β=-0.151,95%CI-0.253–-0.048,P=0.004)were independently correlated with a decrease in the ln[low frequency/high frequency ratio].In the multivariate linear regression model with ln[high frequency(ms^(2))]or ln[RMSSD(ms)]as dependent variable,after adjusting the relevant factors,serum phosphate level was independently correlated with ln[RMSSD(ms)](β=-0.421,95%CI-0.777–-0.065,P=0.021)or ln[high frequency(ms^(2))](β=-0.752,95%CI-1.325–-0.180,P=0.010).Conclusions Hyperphosphatemia is an independent influencing factor of parasympathetic nervous system in MHD patients.Higher NT-proBNP is associated with lower SDNN and lower ratio of low frequency/high frequency,so serum phosphate control and volume control should be highlighted.Age is associated with autonomic dysfunction in MHD patients,so more attention should be paid to elder patients.