合并肾损害高血压患者早期风险评估和降压疗效差异评价

发布时间：2018-04-17 23:37

本文选题：高血压 + 肾损害　；参考：《中南大学》2014年博士论文

【摘要】：目的： 1.筛选并探讨高血压患者早期肾损害的的相关危险因素,建立基于数据挖掘方法的早期肾损害预警模型； 2.调查合并重度肾损害高血压患者用药及降压达标情况,建立基于定量药理学方法评价氨氯地平的降压疗效差异模型。方法： 1.早期肾损害高血压患者风险评估的研究：借助“高血压专科门诊电子信息管理系统”,前瞻性地收集未治疗高血压患者的人口学资料、动态血压参数、血生化和血常规指标建立临床数据库,单因素和多因素Logistic回归方法筛选出早期肾损害的的危险因素,再运用人工神经网络和随机森林算法构建预警评估系统,采用交叉验证方法评价模型的稳定性和可靠性,并进行Wilcox检验以确定高血压患者早期肾损害的最佳风险评估模型。 2.合并重度肾损害高血压患者降压疗效差异研究：借助已建立的“中华肾实质性高血压数据库”,通过体格检查、实验室检验,动态血压监测等手段收集重度肾损害高血压患者225例,分析该人群临床用药以及不同血压监测手段的降压达标情况。采取整群抽样法选择68例患者,以氨氯地平为模型药物干预治疗8周,进行药动学和药效学指标检测,使用NONMEM7.2软件并基于FOCEI的方法,建立氨氯地平治疗的群体药动学/群体药效学模型并进行验证。结果： 1.动态血压参数中夜间血压水平、血压昼夜节律及血压变异性与ACR密切相关(P0.05)；夜间血压下降率是早期肾损害发生的独立危险因素(β值-0.252,P0.05)。 2.ACR与代谢综合征组分之间有显著相关性(P0.05),ACR阳性患者随着代谢组分个数的增多而增加(P0.05)；FBG受损、HDL降低和MS均可增加早期肾损害的风险(P0.05)。 3.ACR与RDW水平密切相关(P0.05),ACR阳性患者随着RDW水平增高而增多(P0.05)。 4.早期肾损害预警模型因变量(Y):mAlb_yn,经过筛选后的自变量集合：'dipping_4','SBP_night_down','MS count','RDW';即血压昼夜节律、夜间收缩压下降率、代谢组分个数以及红细胞分布宽度是重要的预警因子(P0.05)。 5.合并重度肾损害高血压患者异常血压节律比率大96.89%(P0.05)；钙拮抗剂使用率高达92.71%(P0.05)。 6.重度肾损害患者诊室血压SBP、DBP达标率分别为29.30%、20.82%,24h平均血压达标率分别为16.52%、16.96%,白昼平均血压达标率分别为25.00%、26.79%,夜间血压率达标分别为10.27%、8.48%(P0.05)。联合用药达标率高于单一用药(P0.05)。 7.氨氯地平降压疗效差异的后天性原因包括年龄、体重、吸烟、饮食、合并用药和肾功能损害的程度,后两者是重要的影响因素(P0.05)。 8.重度肾损害高血压患者氨氯地平治疗ESBP拟合结果：患者治疗2周时SBP降低值为25.9mmHg,8周时达最大效应为32.6mmHg,获得最大降低SBP效应50%的氨氯地平血药浓度为7.71ng/mL; EDBP拟合结果：治疗2周时DBP降低值为3.4mmHg,8周达最大效应为13.6mmHg,得到最大降低DBP效应50%的氨氯地平血药浓度为13.4ng/mL。结论： 1.血压昼夜节律异常、代谢组分个数和红细胞分布宽度是高血压患者早期肾损害的预警指标,基于新型数据挖掘的风险评估模型稳定可靠。 2.重度肾损害高血压患者不同血压指标达标率低(以夜间为甚),氨氯地平是该人群最常见的降压药物,基于定量药理学氨氯地平治疗8周时的药物浓度-效应模型稳定可靠。
[Abstract]:Purpose :

1 . screening and exploring relevant risk factors of early renal impairment in patients with hypertension , and establishing early warning model of early renal impairment based on data mining method ;

2 . To investigate the antihypertensive effect of amlodipine in patients with severe renal impairment and hypertension , and to establish a quantitative pharmacology method to evaluate the effect of amlodipine on hypertension .

Method :

1 . The risk assessment of early renal impairment was studied : Using the Electronic Information Management System of Hypertension Specialty Clinic , the risk factors of early renal impairment were selected prospectively by establishing clinical database , dynamic blood pressure parameter , blood biochemistry and blood routine index . Using artificial neural network and stochastic forest algorithm to construct early warning evaluation system , the stability and reliability of the model were evaluated by cross validation method , and Wilcox test was conducted to determine the best risk assessment model for early renal impairment in patients with hypertension .

2 . The effect of hypertension in patients with severe renal impairment was studied by means of physical examination , laboratory test , dynamic blood pressure monitoring and so on .

Results :

1 . The nocturnal blood pressure level , the circadian rhythm of blood pressure and the variability of blood pressure were closely related to ACR ( P0.05 ) .
The rate of nocturnal blood pressure decline was an independent risk factor for early renal impairment ( 尾 = 0.252 , P0.05 ) .

2 . There was a significant correlation between ACR and metabolic syndrome ( P0.05 ) , and ACR - positive patients increased with the increase of the number of metabolic components ( P0.05 ) .
FBG was damaged , HDL decreased and MS increased the risk of early renal impairment ( P0.05 ) .

3 . ACR was closely related to RDW ( P0.05 ) , and ACR - positive patients increased with the increase of RDW ( P0.05 ) .

4 . The early - warning model of early renal impairment ( Y ) : mALB _ yn , the self - variable set after screening : ' nocturnal _ 4 ' , ' SBP _ night _ down ' , ' MS count ' , ' RDW ' ; that is , the circadian rhythm of blood pressure , the rate of nocturnal systolic blood pressure , the number of metabolic components and the width of red blood cell were important early - warning factors ( P0.05 ) .

5 . The rate of abnormal blood pressure in patients with severe renal impairment was 96.89 % ( P0.05 ) .
The utilization rate of calcium antagonists was up to 92.71 % ( P0.05 ) .

6 . SBP and DBP were 29.30 % , 20.82 % , 25.00 % , 26.79 % and 10.27 % and 8.48 % respectively ( P0.05 ) .

7 . The reasons for the difference of the curative effect of amlodipine were the age , weight , smoking , diet , concomitant medication and the degree of renal impairment , both of which were important factors ( P0.05 ) .

8 . Treatment of ESBP with amlodipine in patients with severe renal impairment : SBP decreased to 25.9mmHg at 2 weeks , and the maximal effect was 32.6mmHg at 8 weeks . The results showed that the concentration of amlodipine was 7.71 ng / mL at 8 weeks . The results showed that the maximum DBP was 3.4 mmHg at 2 weeks , and the maximal effect was 13.6mmHg , and the concentration of amlodipine was 13.4 ng / mL . Conclusion :

1 . Abnormal circadian rhythm of blood pressure , the number of metabolic components and the width of red blood cell were the early warning indexes of early renal impairment in patients with hypertension , and the risk assessment model based on the new data mining was stable and reliable .

2 . Different blood pressure indexes of patients with severe renal impairment were low ( at night ) , amlodipine was the most common antihypertensive drug in the population , and the drug concentration - effect model was stable and reliable at 8 weeks based on the quantitative pharmacological amlodipine treatment .

【学位授予单位】：中南大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R692;R544.1

【参考文献】