【作者】 李晨；

【导师】 童嘉毅；

【作者基本信息】 东南大学 ， 临床医学（专业学位）， 2019， 硕士

【摘要】 背景:冠状动脉粥样硬化是一种复杂的炎症性疾病,是大多数心血管疾病的病理基础,冠状动脉粥样硬化可进一步使冠状动脉狭窄以及完全阻塞,或(和)因冠状动脉功能性改变导致心肌缺血缺氧或坏死从而导致冠心病(Coronary artery disease,CAD)等一系列心血管事件的发生,严重危害人类健康,给社会造成巨大的经济负担。目前针对冠心病的确诊手段是通过冠状动脉造影,但针对冠状动脉粥样硬化严重程度没有一个较为可靠的生化学方面的检测指标。成纤维细胞生长因子23(Fibroblast growth factor 23,FGF23)是磷酸盐和维生素D代谢的循环调节剂,与冠状动脉钙化有关,在心血管疾病的发病机制中起着重要作用。本研究通过测定循环中FGF23浓度分析其在评价冠状动脉粥样硬化严重程度的临床价值。目的:本研究的目的是FGF23在评价冠状动脉粥样硬化严重程度的临床价值分析。方法:本研究以东南大学附属中大医院心血管内科2018年3月至2018年10月住院期间通过冠状动脉造影检查明确有冠状动脉粥样硬化患者为研究对象,采集研究对象的一般资料、实验室检查指标、既往史、入院前用药情况等信息,结合冠状动脉造影(Coronary angiography,CAG)结果,将冠心病定义为冠状动脉主要分支中至少有一支及以上狭窄直径≥50%,并分为CAD组和非CAD组。参考Gensini评分评价冠脉病变程度:将病变血管分为左主干、左前降支、左回旋支和右冠状动脉;对每支血管病变程度进行定量评定,最终积分为各分支积分之和。再根据三分位法将Gensini评分分为低分组、中分组和高分组。采用酶联免疫吸附试验(Enzyme Linked Immunoorbent Assay,ELISA)法测定血FGF23水平。比较冠心病组与非冠心病组的一般资料和临床信息,偏态分布资料用中位数(四分位间距),即Md(IQR)表示,采用秩和检验比较两组之间FGF23浓度的差异性,应用多因素Logistic回归分别比较FGF23与冠心病和Gensini评分各组间的相关性。结果:(1)FGF23在冠心病组和非冠心病组中浓度分别为35.66(28.75,61.08)pg/ml,34.44(24.39,47.46)pg/ml,具有统计学差异(P<0.05),(2)FGF23在Gensini评分低分组、中分组和高分组中的浓度分别为33.66(24.07,45.28)pg/ml,32.63(28.80,58.22)pg/ml,36.96(30.33,62.52)pg/ml,其中低分组与中分组相比,差异无统计学意义(P>0.05),低分组与高分组相比,高分组FGF23浓度比低分组高,具有统计学差异(P<0.01),高分组与中分组相比,差异没有统计学意义(P>0.05)。(3)经多因素二分类Logistic回归分析发现FGF23水平的升高与冠心病的发生存在相关性,是冠心病的独立相关因素,在调整年龄、性别、吸烟史、高血压病史、总胆固醇(Total cholesterol,TC)、低密度脂蛋白(Low density lipoprotein,LDL)、高密度脂蛋白(High density lipoprotein,LDL)、血糖、降糖药物服用史、降压药物服用史、降脂药物服用史因素后,FGF23与冠心病仍有正相关性(OR=1.020,95%CI:1.006-1.035,P=0.006)。Gensini评分低分组、中分组和高分组经无序多分类Logistic回归分析发现,中分组与低分组比较,在调整年龄、性别、吸烟史、高血压病史、糖尿病病史、高脂血症病史、降糖药物服用史、降压药物服用史、降脂药物服用史因素后,FGF23仍与Gensini评分呈正相关(OR=1.027,95%CI:1.010-1.044,P=0.002),高分组与低分组比较,在调整上述因素后,FGF23仍与Gensini评分呈正相关(OR=1.030,95%CI:1.012-1.048,P=0.001),是Gensini评分的独立正相关因子。结论:FGF23与冠状动脉粥样硬化病变严重程度密切相关,并且是冠心病的重要相关因素。临床上通过测定FGF23浓度在冠状动脉粥样硬化严重程度的病情评估有一定价值。更多还原

【Abstract】 Background:Coronary atherosclerosis,a complex inflammatory disease,which is the pathological basis of most cardiovascular diseases.Coronary atherosclerosis can further narrow and completely occlude coronary arteries.Myocardial ischemia,hypoxia or necrosis leads to a series of cardiovascular events such as coronary artery disease(CAD),due to functional changes in the coronary arteries,which seriously endangers human health and imposes a huge economic burden on society.At present,the diagnosis of coronary heart disease is through coronary angiography,but there is no reliable biochemical test for the severity of coronary atherosclerosis.Fibroblast growth factor 23(FGF23)is a circulating regulator of phosphate and vitamin D metabolism,which is involved in coronary artery calcification and plays an important role in the pathogenesis of cardiovascular disease.This study analyzed the clinical value of the severity of coronary atherosclerosis by measuring the concentration of FGF23 in the circulation.Objective:The purpose of this study was to analyze the clinical value of FGF23 in assessing the severity of coronary atherosclerosis.Methods:In this study,patients with coronary atherosclerosis were enrolled in the Department of Cardiology,Zhongda Hospital,Southeast University,from March 20 to October 2018.The general information of past history,pre-hospital medication,general data and laboratory examinations of the subjects were collected.Coronary heart disease is defined as at least one or more of the main branches of the coronary artery ≥50% according to coronary angiography(CAG)results,and further divided the result into CAD group and non-CAD groups.The Gensini score was used to evaluate the degree of coronary lesions: the lesions were divided into left main artery,left anterior descending artery,left circumflex artery and right coronary artery.The degree of lesions in each vessel was quantitatively assessed,and the final score was the sum of the scores of each branch.The Gensini score is further divided into low,medium,and high groups according to the tertile method.Blood FGF23 levels were determined by Enzyme Linked Immunosorbent Assay(ELISA).The general data and clinical information between the coronary heart disease group and the non-coronary heart disease group were compared.The skewed distribution data were expressed by the median(interquartile range),ie,Md(IQR).The rank sum test was used to compare the concentration of FGF23 between the two groups.Differences were compared between FGF23 and coronary heart disease or FGF23 and Gensini scores by multivariate logistic regression respectively.Results:(1)The concentrations of FGF23 in the coronary heart disease group and the non-coronary heart disease group were 35.66(28.75,61.08)pg/ml and 34.44(24.39,47.46)pg/ml,respectively,with statistical difference(P<0.05).(2)The concentrations of FGF23 in the low,medium and high groups of the Gensini score were 33.66(24.07,45.28)pg/ml,32.63(28.80,58.22)pg/ml,36.96(30.33,62.52)pg/ml,respectively.There was no significant difference between the low group and the medium group(P>0.05).Compared with the low group,the high group FGF23 concentration was higher than the low group,which was statistically different(P<0.01).There was also no statistically significant difference between the high group and the medium group(P>0.05).(3)Multivariate logistic regression analysis showed that there was a correlation between the increase of FGF23 level and the occurrence of coronary heart disease,which was an independent related factor of coronary heart disease.It was adjusted in age,gender,smoking history,history of hypertension,total Total cholesterol(TC),low density lipoprotein(LDL),high density lipoprotein(LDL),blood glucose,hypoglycemic medication history,antihypertensive medication history,lipid-lowering drugs history,there was still a positive correlation between FGF23 and coronary heart disease(OR=1.020,95% CI: 1.006-1.035,P=0.006).The low-group,medium-group and high-group of Gensini scores were analyzed by disordered multi-class logistic regression analysis found that comparison between medium-group and low-group,after the adjustment for age,gender,smoking history,history of hypertension,diabetes,hyperlipidemia,history of hypoglycemic agents,antihypertensive medication,lipid-lowering medication history,FGF23 was still positively correlated with Gensini score(OR=1.027,95% CI: 1.010-1.044,P=0.002).Comparison between high-group and low-group after adjusting for the above factors,FGF23 was still positively correlated with Gensini score(OR=1.030,95% CI: 1.012-1.048,P=0.001),which is an independent positive correlation factor of Gensini score.Conclusions:FGF23 is closely related to the severity of coronary atherosclerotic lesions and is an important factor in coronary heart disease.It is clinically valuable to determine the severity of coronary atherosclerosis by measuring the concentration of FGF23.更多还原