發(fā)布時間：2019-06-28 18:18

【摘要】：背景：血漿氮末端腦利鈉肽前體(NT-proBNP)是一種主要來源于心臟的肽類激素,當(dāng)心臟負(fù)荷加重或室壁張力增加時釋放入血,在心衰的診斷和鑒別診斷、預(yù)后評估、指導(dǎo)治療等方面具有重要價值。目前血漿NT-proBNP的預(yù)后價值研究主要是在心功能不全患者中完成,而在心血管事件風(fēng)險相對較低的普通人群中,雖然也有一些研究認(rèn)為NT-proBNP是死亡和心血管事件風(fēng)險的獨立預(yù)測因素,但證據(jù)還并不充分。另外在高齡老年人(≥80歲)中NT-proBNP的預(yù)后價值還不明確。本研究擬探討血漿NT-proBNP在死亡和心血管事件風(fēng)險較低的普通人群和風(fēng)險較高的高齡老年人(≥80歲)群中的預(yù)后價值。方法：本研究為前瞻、隊列研究,研究人群分別為北京市石景山區(qū)蘋果園社區(qū)1859名45歲以上表觀健康的當(dāng)?shù)爻Ｗ【用窈驮诮夥跑娍傖t(yī)院老年病房住院或查體的861例內(nèi)科情況穩(wěn)定的高齡老年人。第一組人群2007年9月至2009年1月完成基線數(shù)據(jù)采集,2013年4月至9月完成隨訪；第二組人群2007年11月至2010年10月完成基線數(shù)據(jù)采集,2015年12月至2016年1月完成隨訪。基線時記錄所有研究對象的年齡、性別,疾病史和用藥情況,測量身高、體重,抽血查SCr、血脂、血糖和血漿NT-proBNP等,高齡老年人均完成心臟超聲檢查.記錄隨訪結(jié)束時死亡和主要心血管事件,用Cox比例風(fēng)險回歸模型分析NT-proBNP對這兩組人群的死亡和心血管事件風(fēng)險的預(yù)測價值。結(jié)果：在普通人群中,基線平均年齡61.4±11.4歲(范圍：45-98歲),平均NT-proBNP濃度41.6pg/mL(IQR,19.8-81.9pg/mL),多元線性回歸分析顯示女性、老年和收縮壓與NT-proBNP正相關(guān),eGFR和舒張壓與NT-proBNP負(fù)相關(guān).平均隨訪4.8年后,死亡52例(3.6%),發(fā)生心血管事件154例(10.3%),調(diào)整年齡、性別、腎功能、Hs-CRP及其他傳統(tǒng)心血管危險因素后,Cox比例風(fēng)險回歸模型分析顯示NT-proBNP水平升高與全因死亡(HR=3.59,95% CI,1.22-8.81; p＜0.001)和心血管事件的風(fēng)險(HR=3.16,95% CI,1.64-6.09;p＜0.001)顯著相關(guān)。ROC曲線分析發(fā)現(xiàn)NT-proBNP預(yù)測死亡和心血管事件的最佳界值是81.7pg/mL.亞組分析發(fā)現(xiàn)NT-proBNP是65歲以上老年人全因死亡[HR=1.68,95%CI, 1.22-2.31; p=0.001]和心血管事件風(fēng)險(HR=1.4,95%CI,1.17-1.68; p0.001)的獨立預(yù)測因素。在高齡老年人群中,基線平均年齡86.6±3.0歲(范圍：80-100歲),平均NT-proBNP濃度770.26±817.72pg/mL,多元線性回歸分析顯示NT-proBNP與年齡、AF、SCr、尿素氮、LAD和應(yīng)用p受體阻滯劑正相關(guān),與eGFR、TG、血色素、血漿白蛋白、LVEF和BMI負(fù)相關(guān)。中位隨訪5.3年(IQR2.7-6.6年)后,死亡353例(48.8%),發(fā)生心血管事件202例(27.9%),調(diào)整年齡、性別、血色素、血漿白蛋白及其他傳統(tǒng)心血管危險因素后,Cox比例風(fēng)險回歸模型分析顯示血漿NT-proBNP是全因死亡和心血管事件風(fēng)險獨立預(yù)測因素,但是增加調(diào)整心臟超聲相關(guān)參數(shù)后,獨立預(yù)測作用消失。ROC曲線分析發(fā)現(xiàn)預(yù)測全因死亡和心血管事件風(fēng)險的最佳界值為405.8pg/mL.亞組分析發(fā)現(xiàn),NT-proBNP是CKD患者全因死亡的獨立預(yù)測因素(HR=1.85,95%CI 1.090-3.141; p=0.023),在調(diào)整心血管系統(tǒng)藥物和心臟超聲相關(guān)參數(shù)后,獨立預(yù)測心血管事件的作用消失；是高齡老年左室肥厚患者死亡的獨立預(yù)測因素(HR=1.585,95%CI 0.962-2.612; p=0.041),但不是該亞組患者主要心血管事件的獨立預(yù)測因素(HR=1.165,95%CI 0.558-2.432; p=0.684).結(jié)論：多種因素影響血漿NT-proBNP濃度,應(yīng)用NT-proBNP作為診斷、預(yù)后評估或指導(dǎo)治療的指標(biāo)時均應(yīng)考慮這些因素。不論是死亡或心血管事件風(fēng)險較低的普通人群還是風(fēng)險較高的高齡老年人群, NT-proBNP都有獨立預(yù)測死亡和心血管事件風(fēng)險的作用,但有心臟超聲結(jié)果時,NT-proBNP的預(yù)測能力減弱。本研究中,普通人或高齡老年人中NT-proBNP的最佳預(yù)后界值分別為81.7pg/mL和405.8pg/mL,還有待更多研究證實。NT-proBNP是高齡CKD或左室肥厚患者全因死亡的獨立預(yù)測因子。
[Abstract]:BACKGROUND: The plasma N-terminal brain natriuretic peptide (NT-proBNP) is a kind of peptide hormone which is mainly derived from the heart. It is of great value in the diagnosis and differential diagnosis of heart failure, the evaluation of the prognosis and the guiding treatment when the load of the heart is increased or the tension of the chamber wall is increased. The current study on the prognostic value of plasma NT-proBNP is mainly done in the patients with cardiac insufficiency, while in the general population with relatively low risk of cardiovascular events, although there are some studies that NT-proBNP is an independent predictor of the risk of death and cardiovascular events, the evidence is not sufficient. In addition, the prognostic value of NT-proBNP in the elderly (80-year-old) is not clear. The purpose of this study is to explore the prognostic value of plasma NT-proBNP in the elderly (80-year-old) with lower risk of death and cardiovascular events and higher risk. Methods: This study is a prospective and cohort study. The study population is an elderly resident of 1859 local residents in Shijingshan District, Beijing, with apparent health and 861 cases of internal medicine, which are hospitalized or examined in the old ward of the General Hospital of the PLA. The first group completed the baseline data collection from September 2007 to January 2009 and completed the follow-up from April to September 2013; the second group completed the baseline data collection from November 2007 to October 2010, and the follow-up was completed from December 2015 to January 2016. The age, sex, disease history and medication of all study subjects were recorded at baseline, and height, body weight, blood draw, SCr, blood lipid, blood sugar and plasma NT-proBNP were measured. The death and major cardiovascular events were recorded at the end of the follow-up, and the predictive value of NT-proBNP for the risk of death and cardiovascular events in both groups was analyzed by a Cox proportional hazard regression model. Results: In the general population, the mean age of the baseline was 61.4 to 11.4 years (range:45 to 98 years), the average NT-proBNP concentration was 41.6 pg/ mL (IQR, 19.8-81.9 pg/ mL), and the multivariate linear regression analysis showed that the elderly and the systolic blood pressure were positively correlated with NT-proBNP, and the eGFR and the diastolic blood pressure were negatively correlated with NT-proBNP. After an average follow-up of 4.8 years,52 patients (3.6%) died,154 (10.3%) of the cardiovascular events, age, sex, renal function, Hs-CRP and other traditional cardiovascular risk factors, the Cox proportional risk regression model analysis showed that the level of NT-proBNP and all-cause death (HR = 3.59,95% CI, 1.22-8.81; The risk of cardiovascular events (HR = 3.16,95% CI, 1.64-6.09; p <0.001) was significantly related. The ROC curve analysis found that the optimal margin for NT-proBNP to predict death and cardiovascular events was 81.7 pg/ mL. The subgroup analysis found that NT-proBNP was an independent predictor of all-cause death[HR = 1.68,95% CI, 1.22-2.31; p = 0.001] and cardiovascular event risk (HR = 1.4,95% CI, 1.17-1.68; p0.001) for older persons over 65 years of age. In the elderly population, the mean age of the baseline was 86.6 to 3.0 years (range:80 to 100 years), the average NT-proBNP concentration was 770.26 to 817.72 pg/ mL, and the multivariate linear regression analysis showed that NT-proBNP was positively correlated with age, AF, SCr, urea nitrogen, LAD, and p-receptor blockers, with eGFR, TG, hemoglobin, plasma albumin, There was a negative correlation between LVEF and BMI. After a median follow-up of 5.3 years (IQR2.7-6.6 years),353 cases (48.8%) died,202 (27.9%) of the cardiovascular events occurred, and after the age, sex, hemoglobin, plasma albumin and other traditional cardiovascular risk factors were adjusted, Cox proportional risk regression model analysis showed that plasma NT-proBNP was an independent predictor of all-cause mortality and cardiovascular events, but the independent predictor disappeared after adjusting the cardiac ultrasound-related parameters. The ROC curve analysis found that the best margin for predicting all-cause death and cardiovascular events was 405.8 pg/ mL. The subgroup analysis found that NT-proBNP was an independent predictor of all-cause mortality in patients with CKD (HR = 1.85,95% CI 1.090-3.141; p = 0.023); after the cardiovascular system drug and the cardiac ultrasound-related parameters were adjusted, the effect of independent prediction of cardiovascular events was disappeared; an independent predictor of death in the elderly with left ventricular hypertrophy (HR = 1.585,95% CI 0.962-2.612; P = 0.041), but not independent predictors of major cardiovascular events in the subgroup (HR = 1.165,95% CI 0.558-2.432; p = 0.684). Conclusion: The factors that influence the concentration of NT-proBNP in plasma and the application of NT-proBNP as the index of diagnosis, prognosis and treatment should be taken into account. NT-proBNP is an independent predictor of the risk of death and cardiovascular events, both in the general population with a lower risk of death or cardiovascular events, but with a reduced prediction of NT-proBNP when there is a cardiac ultrasound. In this study, the best prognostic value for NT-proBNP in the elderly or the elderly was 81.7 pg/ mL and 405.8 pg/ mL, respectively, and more studies to be confirmed. NT-proBNP is an independent predictor of all-cause mortality in elderly patients with CKD or left ventricular hypertrophy.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R54

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