【作者】 张皓；

【导师】 郑杨；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2025， 硕士

【摘要】 目的:本研究结合双样本孟德尔随机化(MR)和现况调查方法,探讨增殖性糖尿病视网膜病变(PDR)与多种心血管疾病(包括冠心病)之间的因果关联。方法:本研究采用双样本孟德尔随机化方法,分析增殖性糖尿病视网膜病变(PDR)与多种心血管疾病(包括冠心病总事件、心绞痛、心肌梗死、慢性心力衰竭、心律失常、缺血性卒中和二尖瓣功能不全)的潜在因果联系。同时,纳入2014年9月至2024年9月于吉林大学第一医院接受眼底检查和冠状动脉造影的患者进行现况调查,以验证孟德尔随机化分析结果的可靠性。研究对象根据视网膜病变程度分为无糖尿病视网膜病变(NDR)、非增殖性糖尿病视网膜病变(NPDR)和PDR三组。收集患者的基线信息、实验室检测数据、眼底照片和冠状动脉造影结果,并计算Gensini评分。通过差异性分析和相关性分析,探讨不同糖尿病视网膜病变(DR)分期与冠状动脉病变程度(以Gensini评分和冠状动脉病变支数为指标)及心脏功能相关指标(如肌钙蛋白和利钠肽)之间的相关性,以评估糖尿病视网膜病变对冠状动脉病变严重程度的影响。结果:1、孟德尔随机化分析显示,PDR与心绞痛和心肌梗死的发生有潜在关联(心绞痛:OR=1.029,95%CI=1.007–1.052,P=0.011;心肌梗死:OR=1.036,95%CI=1.005–1.069,P=0.024),但与其他心血管疾病无显著关联。MR-Egger回归、WM法、MR-RAPS法均得出了一致的结论,且敏感性分析未发现异质性与多效性。2、现况调查发现,与NDR组相比,NPDR组和PDR组患者的年龄更大,糖尿病病程更长,白细胞计数(WBC)、肌酐(Cr)、尿素氮(BUN)、肌钙蛋白(Tn)、氨基末端B型利钠肽前体(NT-pro BNP)、D-二聚体(D-D)、纤维蛋白原(FIB)水平更高,而胆红素(包括TBIL、IBIL、DBIL)、转氨酶(包括AST、ALT)、总蛋白(TP)、白蛋白(ALB)、红细胞计数(RBC)、血红蛋白(Hb)水平更低(P<0.05)。3、冠状动脉病变的血管数量随糖尿病视网膜病变严重程度增加而增加,PDR组最多,NDR组最少(P<0.001)。4、糖尿病视网膜病变分期与冠状动脉Gensini评分、病变支数及心脏损伤标志物(如Tn、NT-pro BNP)呈正相关。结论:1、孟德尔随机化分析支持PDR与心绞痛和心肌梗死之间存在因果关系。2、与NDR组相比,PDR和NPDR组患者的年龄更大,糖尿病病程更长,且心脏损伤标志物水平更高。3、冠状动脉病变的血管数量和严重程度随着糖尿病视网膜病变的加重而增加。更多还原

【Abstract】 Objective:This study integrates two-sample Mendelian randomization and cross-sectional survey methods to investigate the causal associations between proliferative diabetic retinopathy(PDR)and various cardiovascular diseases,including coronary heart disease.Methods:This study employed a two-sample Mendelian randomization(MR)approach to investigate the potential causal relationships between proliferative diabetic retinopathy(PDR)and various cardiovascular diseases,including coronary heart disease(total events),angina pectoris,myocardial infarction,chronic heart failure,arrhythmia,ischemic stroke,and mitral valve insufficiency.Additionally,a cross-sectional survey was conducted among patients who underwent fundus examination and coronary angiography at the First Hospital of Jilin University between September 2014 and September 2024 to verify the reliability of the findings from the Mendelian randomization analysis.The study population was stratified into three groups based on the severity of diabetic retinopathy:no diabetic retinopathy(NDR),non-proliferative diabetic retinopathy(NPDR),and PDR.Baseline information,laboratory test results,fundus photographs,and coronary angiography outcomes were collected from the participants,and the Gensini score was calculated.Differential and correlation analyses were performed to explore the associations between different stages of diabetic retinopathy(DR)and the severity of coronary artery disease(assessed by Gensini score and the number of coronary artery lesions)as well as cardiac function-related indicators(such as troponin T and NT-pro BNP),thereby evaluating the impact of diabetic retinopathy on the severity of coronary artery disease.Results:1.Mendelian randomization analysis indicated that PDR may have potential associations with the occurrence of angina pectoris(OR=1.029,95%CI=1.007–1.052,P=0.011)and myocardial infarction(OR=1.036,95%CI=1.005–1.069,P=0.024),but not with other cardiovascular diseases.Consistent conclusions were drawn using MR-Egger regression,WM method,and MR-RAPS method,and no heterogeneity or pleiotropy was detected in the sensitivity analyses.2.The current survey has found that compared with the NDR group,patients in the NPDR and PDR groups are older and have a longer duration of diabetes,higher levels of white blood cell count(WBC),creatinine(Cr),blood urea nitrogen(BUN),troponin(Tn),N-terminal pro-Brain natriuretic peptide(NT-pro BNP),D-dimer(D-D),and fibrinogen(FIB),and lower levels of bilirubin(including TBIL,IBIL,and DBIL),transaminases(including AST and ALT),total protein(TP),albumin(ALB),red blood cell count(RBC),and hemoglobin(Hb)(P<0.05).3.The number of coronary artery lesions increased with the severity of diabetic retinopathy,with the highest number in the PDR group and the lowest in the NDR group(P<0.001).4.The severity of diabetic retinopathy was positively correlated with coronary artery Gensini score,number of affected vessels,and cardiac injury biomarkers(e.g.,Tn,NT-pro BNP).Conclusions:1.Mendelian randomization analysis supports a causal relationship between PDR and the occurrence of angina pectoris and myocardial infarction.2.Compared with the NDR group,patients in the PDR and NPDR groups were older,had a longer duration of diabetes,and exhibited higher levels of cardiac injury markers.3.The number and severity of coronary artery lesions increased with the worsening of diabetic retinopathy.更多还原