本文選題：高血壓 + 腎損害��； 參考：《中南大學(xué)》2014年博士論文

【摘要】：目的： 1.篩選并探討高血壓患者早期腎損害的的相關(guān)危險(xiǎn)因素,建立基于數(shù)據(jù)挖掘方法的早期腎損害預(yù)警模型； 2.調(diào)查合并重度腎損害高血壓患者用藥及降壓達(dá)標(biāo)情況,建立基于定量藥理學(xué)方法評價(jià)氨氯地平的降壓療效差異模型。 方法： 1.早期腎損害高血壓患者風(fēng)險(xiǎn)評估的研究：借助“高血壓專科門診電子信息管理系統(tǒng)”,前瞻性地收集未治療高血壓患者的人口學(xué)資料、動態(tài)血壓參數(shù)、血生化和血常規(guī)指標(biāo)建立臨床數(shù)據(jù)庫,單因素和多因素Logistic回歸方法篩選出早期腎損害的的危險(xiǎn)因素,再運(yùn)用人工神經(jīng)網(wǎng)絡(luò)和隨機(jī)森林算法構(gòu)建預(yù)警評估系統(tǒng),采用交叉驗(yàn)證方法評價(jià)模型的穩(wěn)定性和可靠性,并進(jìn)行Wilcox檢驗(yàn)以確定高血壓患者早期腎損害的最佳風(fēng)險(xiǎn)評估模型。 2.合并重度腎損害高血壓患者降壓療效差異研究：借助已建立的“中華腎實(shí)質(zhì)性高血壓數(shù)據(jù)庫”,通過體格檢查、實(shí)驗(yàn)室檢驗(yàn),動態(tài)血壓監(jiān)測等手段收集重度腎損害高血壓患者225例,分析該人群臨床用藥以及不同血壓監(jiān)測手段的降壓達(dá)標(biāo)情況。采取整群抽樣法選擇68例患者,以氨氯地平為模型藥物干預(yù)治療8周,進(jìn)行藥動學(xué)和藥效學(xué)指標(biāo)檢測,使用NONMEM7.2軟件并基于FOCEI的方法,建立氨氯地平治療的群體藥動學(xué)/群體藥效學(xué)模型并進(jìn)行驗(yàn)證。 結(jié)果： 1.動態(tài)血壓參數(shù)中夜間血壓水平、血壓晝夜節(jié)律及血壓變異性與ACR密切相關(guān)(P0.05)；夜間血壓下降率是早期腎損害發(fā)生的獨(dú)立危險(xiǎn)因素(β值-0.252,P0.05)。 2.ACR與代謝綜合征組分之間有顯著相關(guān)性(P0.05),ACR陽性患者隨著代謝組分個(gè)數(shù)的增多而增加(P0.05)；FBG受損、HDL降低和MS均可增加早期腎損害的風(fēng)險(xiǎn)(P0.05)。 3.ACR與RDW水平密切相關(guān)(P0.05),ACR陽性患者隨著RDW水平增高而增多(P0.05)。 4.早期腎損害預(yù)警模型因變量(Y):mAlb_yn,經(jīng)過篩選后的自變量集合：'dipping_4','SBP_night_down','MS count','RDW';即血壓晝夜節(jié)律、夜間收縮壓下降率、代謝組分個(gè)數(shù)以及紅細(xì)胞分布寬度是重要的預(yù)警因子(P0.05)。 5.合并重度腎損害高血壓患者異常血壓節(jié)律比率大96.89%(P0.05)；鈣拮抗劑使用率高達(dá)92.71%(P0.05)。 6.重度腎損害患者診室血壓SBP、DBP達(dá)標(biāo)率分別為29.30%、20.82%,24h平均血壓達(dá)標(biāo)率分別為16.52%、16.96%,白晝平均血壓達(dá)標(biāo)率分別為25.00%、26.79%,夜間血壓率達(dá)標(biāo)分別為10.27%、8.48%(P0.05)。聯(lián)合用藥達(dá)標(biāo)率高于單一用藥(P0.05)。 7.氨氯地平降壓療效差異的后天性原因包括年齡、體重、吸煙、飲食、合并用藥和腎功能損害的程度,后兩者是重要的影響因素(P0.05)。 8.重度腎損害高血壓患者氨氯地平治療ESBP擬合結(jié)果：患者治療2周時(shí)SBP降低值為25.9mmHg,8周時(shí)達(dá)最大效應(yīng)為32.6mmHg,獲得最大降低SBP效應(yīng)50%的氨氯地平血藥濃度為7.71ng/mL; EDBP擬合結(jié)果：治療2周時(shí)DBP降低值為3.4mmHg,8周達(dá)最大效應(yīng)為13.6mmHg,得到最大降低DBP效應(yīng)50%的氨氯地平血藥濃度為13.4ng/mL。結(jié)論： 1.血壓晝夜節(jié)律異常、代謝組分個(gè)數(shù)和紅細(xì)胞分布寬度是高血壓患者早期腎損害的預(yù)警指標(biāo),基于新型數(shù)據(jù)挖掘的風(fēng)險(xiǎn)評估模型穩(wěn)定可靠。 2.重度腎損害高血壓患者不同血壓指標(biāo)達(dá)標(biāo)率低(以夜間為甚),氨氯地平是該人群最常見的降壓藥物,基于定量藥理學(xué)氨氯地平治療8周時(shí)的藥物濃度-效應(yīng)模型穩(wěn)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 .

【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R692;R544.1

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