血浆NT-proBNP对死亡和心血管事件预后价值的研究

发布时间：2019-06-28 18:18

【摘要】：背景：血浆氮末端脑利钠肽前体(NT-proBNP)是一种主要来源于心脏的肽类激素,当心脏负荷加重或室壁张力增加时释放入血,在心衰的诊断和鉴别诊断、预后评估、指导治疗等方面具有重要价值。目前血浆NT-proBNP的预后价值研究主要是在心功能不全患者中完成,而在心血管事件风险相对较低的普通人群中,虽然也有一些研究认为NT-proBNP是死亡和心血管事件风险的独立预测因素,但证据还并不充分。另外在高龄老年人(≥80岁)中NT-proBNP的预后价值还不明确。本研究拟探讨血浆NT-proBNP在死亡和心血管事件风险较低的普通人群和风险较高的高龄老年人(≥80岁)群中的预后价值。方法：本研究为前瞻、队列研究,研究人群分别为北京市石景山区苹果园社区1859名45岁以上表观健康的当地常住居民和在解放军总医院老年病房住院或查体的861例内科情况稳定的高龄老年人。第一组人群2007年9月至2009年1月完成基线数据采集,2013年4月至9月完成随访；第二组人群2007年11月至2010年10月完成基线数据采集,2015年12月至2016年1月完成随访。基线时记录所有研究对象的年龄、性别,疾病史和用药情况,测量身高、体重,抽血查SCr、血脂、血糖和血浆NT-proBNP等,高龄老年人均完成心脏超声检查.记录随访结束时死亡和主要心血管事件,用Cox比例风险回归模型分析NT-proBNP对这两组人群的死亡和心血管事件风险的预测价值。结果：在普通人群中,基线平均年龄61.4±11.4岁(范围：45-98岁),平均NT-proBNP浓度41.6pg/mL(IQR,19.8-81.9pg/mL),多元线性回归分析显示女性、老年和收缩压与NT-proBNP正相关,eGFR和舒张压与NT-proBNP负相关.平均随访4.8年后,死亡52例(3.6%),发生心血管事件154例(10.3%),调整年龄、性别、肾功能、Hs-CRP及其他传统心血管危险因素后,Cox比例风险回归模型分析显示NT-proBNP水平升高与全因死亡(HR=3.59,95% CI,1.22-8.81; p＜0.001)和心血管事件的风险(HR=3.16,95% CI,1.64-6.09;p＜0.001)显著相关。ROC曲线分析发现NT-proBNP预测死亡和心血管事件的最佳界值是81.7pg/mL.亚组分析发现NT-proBNP是65岁以上老年人全因死亡[HR=1.68,95%CI, 1.22-2.31; p=0.001]和心血管事件风险(HR=1.4,95%CI,1.17-1.68; p0.001)的独立预测因素。在高龄老年人群中,基线平均年龄86.6±3.0岁(范围：80-100岁),平均NT-proBNP浓度770.26±817.72pg/mL,多元线性回归分析显示NT-proBNP与年龄、AF、SCr、尿素氮、LAD和应用p受体阻滞剂正相关,与eGFR、TG、血色素、血浆白蛋白、LVEF和BMI负相关。中位随访5.3年(IQR2.7-6.6年)后,死亡353例(48.8%),发生心血管事件202例(27.9%),调整年龄、性别、血色素、血浆白蛋白及其他传统心血管危险因素后,Cox比例风险回归模型分析显示血浆NT-proBNP是全因死亡和心血管事件风险独立预测因素,但是增加调整心脏超声相关参数后,独立预测作用消失。ROC曲线分析发现预测全因死亡和心血管事件风险的最佳界值为405.8pg/mL.亚组分析发现,NT-proBNP是CKD患者全因死亡的独立预测因素(HR=1.85,95%CI 1.090-3.141; p=0.023),在调整心血管系统药物和心脏超声相关参数后,独立预测心血管事件的作用消失；是高龄老年左室肥厚患者死亡的独立预测因素(HR=1.585,95%CI 0.962-2.612; p=0.041),但不是该亚组患者主要心血管事件的独立预测因素(HR=1.165,95%CI 0.558-2.432; p=0.684).结论：多种因素影响血浆NT-proBNP浓度,应用NT-proBNP作为诊断、预后评估或指导治疗的指标时均应考虑这些因素。不论是死亡或心血管事件风险较低的普通人群还是风险较高的高龄老年人群, NT-proBNP都有独立预测死亡和心血管事件风险的作用,但有心脏超声结果时,NT-proBNP的预测能力减弱。本研究中,普通人或高龄老年人中NT-proBNP的最佳预后界值分别为81.7pg/mL和405.8pg/mL,还有待更多研究证实。NT-proBNP是高龄CKD或左室肥厚患者全因死亡的独立预测因子。
[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.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R54

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