老年人群血管内皮功能的研究及其对心血管事件的影响

发布时间：2018-06-25 05:59

本文选题：高龄 + 反应性充血指数(RHI)　；参考：《中国人民解放军医学院》2017年博士论文

【摘要】：背景:血管内皮是人体内最大的内分泌器官,具有重要的生理及病理生理功能。内皮功能的损伤,在心血管疾病的进程及最终转归中起到了重要的作用。此前多项研究已经证实血管内皮功能的影响因素与心血管危险该因素相关,主要包括年龄、体重指数、性别、血脂、糖尿病、冠心病、高血压等。并明确了血管内皮功能障碍可能导致远期心血管事件增加。但对于老年群体,是否还有其他可能影响血管内皮功能的因素。以及血管内皮功能对老年人群的心血管事件预测价值,特别是对相对近期的心血管事件预测价值,并不十分清楚。本研究拟探讨血管内皮功能的重要指标-血管反应性充血指数(RHI)在老年人群中的影响因素,以及其对近期(≤2年)心血管事件的单独预测价值以及复合心肾功能指标后的预测价值。方法:本研究为前瞻、队列研究。研究对象为解放军总医院1686名常规查体及住院老年患者。除外研究对象患肿瘤、感染、长期卧床、机械通气、双上臂血压不一致等情况。在2015年2月至7月间完成血管内皮功能的检查及其他包括年龄、疾病史、身高、体重、血压、心率、血液化验指标等结果的收集。将观察对象根据RHI四分位及是否合并冠心病及糖尿病分组,明确影响血管内功能的可能因素。研究对象随访至2017年2月,根据RHI、NT-proBNP、eGFR指标的中位数分为高、低两组,明确各组研究对象在随访期间心血管事件的发生情况。应用Cox比例风险模型评估RHI对近期心血管时间的预测价值。并在RHI的基础上,加入NT-proBNP及eGFR,共同评估此复合指标对近期心血管事件发生的预测价值。结果:在1686例研究对象(平均年龄75.3 ± 10岁)中,诊断血脂紊乱1309人,高血压776人,糖尿病592人,冠心病542人,慢性肾功能不全69人。将研究对象分按照RHI四分位分为四组,结果发现随RHI高的组与低的组相比,年龄更小、吸烟比率更少、患高血压比例更低、患糖尿病比例更低、BMI更低、收缩压更低、空腹血糖更低、糖化血红蛋白更低、总胆固醇更低、高密度脂蛋白胆固醇更高、肌酐更低、NT-proBNP更低、eGFR更高(P for all 0.01)。经单因素分析显示In-RHI (自然对数转换后RHI)与年龄、吸烟、高血压、BMI、舒张压、空腹血糖、全血糖化血红蛋白、胆固醇、低密度脂蛋白胆固醇、肌酐、NT-proBNP呈负相关(P for all 0.05 );与eGFR呈正相关(P0.001 )。多因素线性回归分析显示In-RHI与年龄、吸烟、BMI、糖化血红蛋白、低密度脂蛋白胆固醇、NT-proBNP呈负相关(P for all 0.05 );与eGFR呈正相关(P=0.017 )。将研究对象按照有无冠心病及糖尿病分组,RHI在无冠心病及糖尿病组中,中位数为2.05 (IQR 1.82-2.28 );在单冠心病组中,中位数为1.91 (IQR 1.76-1.96);在单糖尿病组中,中位数为1.56 (IQR 1.52-1.61);在冠心病+糖尿病组中,中位数为1.38 (IQR 1.31-1.42)。无冠心病及糖尿病组与单冠心病组相比,无明显统计学差异(P0.05);而明显高于糖尿病及糖尿病+冠心病组(P0.01)。糖尿病组亦高于糖尿病+冠心病组(P0.01)。ROC曲线提示RHI对冠心病诊断价值不大。经过中位时间为21.6个月的随访,发现发生心血管事件人群中,年龄、糖尿病、冠心病患病率、BMI、糖化血红蛋白、甘油三酯、高密度脂蛋白胆固醇、尿酸、NT-proBNP、eGFR、β受体阻滞剂、ACEI或ARB应用率与未发生心血管事件人群显著不同(P0.05)。发生心血管事件的人群RHI较未发生心血管事件人群更低(P0.001)。采用Cox 比例风险模型分析,校正年龄、BMI、糖尿病、冠心病等因素后,心血管事件发生仅与年龄、RHI、NT-proBNP、eGFR相关(年龄:HR 1.021 95%CI 1.075-1.154, NT-proBNP: HR 1.089 95%CI 1.034-1.161,RHI: HR 0.722 95%CI 0.691-0.844,eGFR: HR 0.958 95%CI 0.858-0.984)。将RHI联合NT-proBNP和(或eGFR)后,对心血管事件的预测价值进一步增加(单独 NT-proBNP C-Statistics=0.592 ( 95%CI 0.524-0.662 ),联合 RHI 后C-Statistics=0.714 ( 95%CI 0.657-0.765 ) , NT-proBNP+eGFR+RHI 后C-Statistics=0.737 (95%CI0.678-0.791 。且对糖尿病和(或)冠心病人群的预测价值更大。结论:在老年人群中,多种因素可影响血管内皮功能。且血管内皮功能对近期心血管事件具有预测价值,联合NT-proBNP和(或eGFR)后,这种预测价值进一步提高。
[Abstract]:Background: vascular endothelium is the largest endocrine organ in the human body and has important physiological and pathophysiological functions. The damage of endothelial function plays an important role in the process and final outcome of cardiovascular disease. Several previous studies have confirmed that the factors affecting vascular endothelial function are related to the risk factors of cardiovascular disease, the main package Including age, body mass index, sex, blood lipid, diabetes, coronary heart disease, hypertension, and so on. It is clear that vascular endothelial dysfunction may lead to an increase in long-term cardiovascular events. But for older groups, there are other factors that may affect vascular endothelial function and the predictive value of intravascular skin function on cardiovascular events in elderly people. This study is not very clear about the predictive value of relative recent cardiovascular events. This study intends to explore the influential factors of vascular endothelial function - the vascular reactive hyperemia index (RHI) in the elderly population, as well as its single pretest value for the recent (less than 2 years) cardiovascular events and the predictive value of the composite heart and kidney function index. Value. Methods: This study was prospective, cohort study. The subjects were 1686 general and hospitalized elderly patients in the General Hospital of the PLA. Except for the cases of cancer, infection, long stay in bed, mechanical ventilation, and the inconsistency of blood pressure in the double upper arm. Between February 2015 and July, the examination of vascular endothelial function and other diseases including age and disease were completed. History, height, weight, blood pressure, heart rate, blood test index and other results. The subjects were determined to affect the intravascular function according to the RHI four subdivision and the grouping of coronary heart disease and diabetes. The subjects were followed up to February 2017, according to the median of the RHI, NT-proBNP, and eGFR indexes. A Cox proportional hazard model was used to evaluate the predictive value of RHI to the recent cardiovascular events. On the basis of RHI, NT-proBNP and eGFR were added to evaluate the predictive value of this composite index on the occurrence of recent cardiovascular events. Results: 1686 subjects (average age 75.3 +. At the age of 10, 1309 people were diagnosed with dyslipidemia, 776 people with hypertension, 592 diabetes, 542 patients with coronary heart disease and 69 chronic renal insufficiency. The subjects were divided into four groups according to RHI four. The results showed that the group with high RHI was younger, less smoking ratio, lower proportion of hypertension, lower proportion of hypertension, lower diabetes ratio, and lower BMI, Lower systolic blood pressure, lower fasting blood sugar, lower glycated hemoglobin, lower total cholesterol, higher density lipoprotein cholesterol, lower creatinine, lower NT-proBNP, and higher eGFR (P for all 0.01). By single factor analysis, In-RHI (natural logarithmic conversion RHI) and age, smoking, hypertension, BMI, diastolic blood pressure, fasting blood glucose, and full blood glucose blood red Protein, cholesterol, low density lipoprotein cholesterol, creatinine, NT-proBNP were negatively correlated (P for all 0.05); positive correlation with eGFR (P0.001). Multivariate linear regression analysis showed that In-RHI was negatively correlated with age, smoking, BMI, glycosylated hemoglobin, low density lipoprotein cholesterol, and NT-proBNP (P for all 0.05); positive correlation with In-RHI. The median of RHI in the group without coronary heart disease and diabetes was 2.05 (IQR 1.82-2.28), and the median was 1.91 (IQR 1.76-1.96) in the mono coronary heart disease group, and the median was 1.56 (IQR 1.52-1.61) in the single diabetic group, and the median of 1.38 (IQR 1.31-1.42) in the group of coronary heart disease and diabetes was 1.38 (IQR 1.31-1.42). There was no significant difference in coronary heart disease and diabetes group compared with single coronary heart disease group (P0.05), but significantly higher than diabetes and diabetes + coronary heart disease group (P0.01). The diabetes group was also higher than the diabetes + coronary heart disease group (P0.01).ROC curve suggesting that RHI was of little value in the diagnosis of coronary heart disease. After a median time of 21.6 months, the heart blood was found. Age, diabetes, coronary heart disease, BMI, glycated hemoglobin, triglycerides, high density lipoprotein cholesterol, uric acid, NT-proBNP, eGFR, beta blockers, ACEI, or ARB were significantly different from those without cardiovascular events (P0.05). The population of cardiovascular events was more RHI than no cardiovascular event population. Lower (P0.001). Using the Cox proportional hazard model analysis, correction of age, BMI, diabetes, coronary heart disease and other factors, cardiovascular events were associated with age, RHI, NT-proBNP, eGFR (age: HR 1.021 95%CI 1.075-1.154, NT-proBNP: HR 1.089 95%CI). The predictive value of RHI combined with NT-proBNP and (or eGFR) for cardiovascular events was further increased (separate NT-proBNP C-Statistics=0.592 (95%CI 0.524-0.662), C-Statistics=0.714 (95%CI 0.657-0.765) after combined RHI, and 0.737 (and for diabetes and / or coronary heart disease) after NT-proBNP+eGFR+RHI. The predictive value is greater. Conclusion: in the elderly, a variety of factors can affect vascular endothelial function. And vascular endothelial function is of predictive value for recent cardiovascular events. This predictive value is further improved after combined with NT-proBNP and (or eGFR).
【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】：R54

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