基于传统危险因素联合多种标记物预测冠心病患者风险的临床研究

发布时间：2018-08-08 15:11

【摘要】：背景:心血管疾病是世界上主要的发病和死亡原因,尤以冠心病为主,发病率逐年上升。近年来研究发现新型标记物可提高心血管事件风险预测能力,目前对联合应用多种标记物的研究较少。研究目的:本研究旨在探讨联合应用新型标记物是否比传统危险因素提供更有价值的预测信息;联合多种病理生理通路的标记物对心血管事件风险预测是否比单个标记物更有优势。研究方法:我们研究了 8种标记物:生长分化因子-15 (GDF-15)和纤维蛋白原(Fibrinogen)评估动脉粥样硬化过程中的炎症反应,N末端B型钠尿肽前体(NT-proBNP)和可溶性ST2(sST2)评估心肌张力及心脏功能,尿酸(UA)评估血管内皮功能,D--二聚体(D-dimer)评估机体凝血功能,妊娠相关蛋白A (PAPP-A)评估动脉粥样硬化斑块稳定性及破裂倾向,肌酐(creatinine)评估肾脏功能。通过炎症、内皮功能状态、心肌张力、凝血功能、斑块稳定和易损性等多种病理生理通路标记物对冠心病患者进行风险评估预测。研究纳入3440名冠心病患者,研究终点包括:心血管死亡、全因死亡、心肌梗死、心力衰竭、脑卒中。对3440名冠心病患者进行中位时间为2.9年的随访,共有419名患者发生临床终点事件。研究结果:通过COX风险比例模型,C指数(C-index )、净重新再分类改善(NRI)及综合区分度改善(IDI)分析,发现各标记物与心血管事件呈显著相关:NT-proBNP为最强的预测因子(NT-proBNP每增加一个标准差[SD]风险比[HR]增加1.67, 95%置信区间[CI] 1.55-1.8, C-index 0.824),GDF-15 (HR 1.74, 95% CI 1.52-2, C-index 0.806), fibrinogen (HR 3.83, 95% CI 2.66-5.52, C-index 0.798), UA (HR 2.7, 95% CI 1.92-3.8, C-index 0.792), D-dimer (HR 1.51, 95% CI 1.37-1.67, C-index 0.8)和creatinine(HR 2.51, 95% CI 2.1-3.01, C-index 0.8)。联合IDI最高的6种血浆标记物(NT-proBNP、GDF-15、 UA、fibrinogen、D-dimer和creatinine)计算一个联合评分。联合多标记物评分与单独应用NT-proBNP相比,NRI和IDI无显著差异,即重新再分类精确性并未显著提高。单个标记物及其联合评分(C-index 0.835)与传统危险因素(C-index 0.768)相比,C-index显著增加(p0.001);联合标记物评分较NT-proBNP,显著提高C-index(p=0.0045 )。研究结论:1. GDF-15、fibrinogen、D-dimer、UA、NT-proBNP 及 creatinine,分别在传统危险因素基础上,显著增加心血管事件及全因死亡的风险预测能力并提高了对冠心病患者危险再分类预测价值。2. NT-proBNP为风险预测能力最强的独立危险因子。联合这6种不同病理生理通路的标记物与单独应用NT-proBNP相比,虽然未显著增加危险再分类信息,但显著提高了临床再发不良心血管事件的风险预测能力。3.对于冠心病患者再发临床缺血事件的风险预测,同时应用多种病理生理通路标记物建立多标记物评分模型较单一病理通路标记物更有优势,可以作为临床上冠心病患者危险分层较为适用的风险预测工具,然而这一多标记物评分模型是否可以应用于临床,尚需另外大样本人群进一步评估验证。
[Abstract]:Background: cardiovascular disease is the main cause of disease and death in the world, especially coronary heart disease. The incidence of cardiovascular disease is increasing year by year. In recent years, research has found that new markers can improve the risk prediction ability of cardiovascular events. At present, there are few studies on the combined application of multiple markers. Is there more valuable prediction information than traditional risk factors; whether markers for multiple pathophysiological pathways are more advantageous than single markers to predict risk of cardiovascular events. Research methods: We studied 8 markers: growth differentiation factor -15 (GDF-15) and fibrinogen (Fibrinogen) for assessing atherosclerosis Inflammation, N terminal B natriuretic peptide precursor (NT-proBNP) and soluble ST2 (sST2) assessment of cardiac muscle tension and cardiac function, uric acid (UA) evaluation of vascular endothelial function, D-- two polymer (D-dimer) assessment of the body's coagulation function, pregnancy related protein A (PAPP-A) assessment of atherosclerotic plaque stability and rupture tendency, creatinine (creatini) NE) assessment of renal function. Multiple pathophysiological markers, such as inflammation, endothelial function, myocardial tension, coagulation function, plaque stability and vulnerability, were used to predict the risk of coronary heart disease. The study was included in 3440 patients with coronary heart disease, including cardiovascular death, whole cause death, myocardial infarction, heart failure, and stroke. A total of 3440 patients with coronary heart disease were followed up for a median time of 2.9 years. A total of 419 patients had clinical endpoint events. The results were: the COX risk ratio model, the C index (C-index), the net reclassification improvement (NRI) and the comprehensive regional diversity improvement (IDI) analysis found that the markers were significantly related to the cardiovascular events: NT-proBNP The strongest predictor (NT-proBNP increases the risk of a standard deviation of [SD] by 1.67, 95% confidence interval [CI] 1.55-1.8, C-index 0.824), GDF-15 (HR 1.74, 95% CI 1.52-2, C-index 0.806), fibrinogen (2.7, 95%, 0.798), 1.51, 95% CI 1.37-1.67, C-index 0.8) and creatinine (HR 2.51, 95% CI 2.1-3.01, C-index 0.8). Combine the highest 6 plasma markers of the United IDI (NT-proBNP, GDF-15, UA, etc.) to calculate a joint score. The single marker and its combined score (C-index 0.835) were significantly increased (p0.001) compared with the traditional risk factors (C-index 0.768); the score of the joint markers was significantly higher than NT-proBNP (p=0.0045). The conclusion was that 1. GDF-15, fibrinogen, D-dimer, UA, NT-proBNP, and p0.001 were in the traditional danger, respectively. On the basis of the factors, the risk prediction ability of cardiovascular events and all causes was significantly increased and the value of the risk reclassification of patients with coronary heart disease was increased by.2. NT-proBNP as the most independent risk factor. The combination of these 6 different pathophysiological pathways was not significantly increased in comparison with the single single application of NT-proBNP. Dangerous reclassification information, but significantly improves the risk prediction ability of clinical recurrent adverse cardiovascular events.3. for the risk prediction of recurrent ischemic events in patients with coronary heart disease, and the use of multiple pathophysiological markers to establish a multi marker score model is more advantageous than a single pathophysiological marker, which can be used as a clinical case. Risk stratification is a more suitable risk prediction tool for patients with coronary heart disease. However, whether the multiple marker score model can be applied to the clinic is still needed for further assessment.
【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】：2017
【分类号】：R541.4

【相似文献】