BACKGROUND Cardiac dysfunction and cardiovascular events are prevalent among patients with chronic kidney disease without overt obstructive coronary artery disease, but the mechanisms remain poorly understood. Coronary microvascular dysfunction has been proposed as a link between abnormal renal function and impairment of cardiac function and cardiovascular events. We aimed to investigate the relations between chronic kidney disease, coronary microvascular dysfunction, cardiac dysfunction, and adverse cardiovascular outcomes. METHODS Patients undergoing cardiac stress positron emission tomography, echocardiogram, and renal function ascertainment at Brigham and Women's Hospital were studied longitudinally. Patients free of overt coronary (summed stress score <3 and without a history of ischemic heart disease), valvular, and end-organ disease were followed up for the adverse composite outcome of death or hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was determined from positron emission tomography. Echocardiograms were used to measure cardiac mechanics: diastolic (lateral and septal E/e') and systolic (global longitudinal, radial, and circumferential strain). Image analyses and event adjudication were blinded. The associations between estimated glomerular filtration rate (eGFR), CFR, diastolic and systolic indices, and adverse cardiovascular outcomes were assessed in adjusted models and mediation analyses. RESULTS Of the 352 patients (median age, 65 years; 63% female; 22% black) studied, 35% had an eGFR <60 mL·min-1·1.73 m-2, a median left ventricular ejection fraction of 62%, and a median CFR of 1.8. eGFR and CFR were associated with diastolic and systolic indices, as well as future cardiovascular events (all P<0.05). In multivariable models, CFR, but not eGFR, was independently associated with cardiac mechanics and cardiovascular events. The associations between eGFR, cardiac mechanics, and cardiovascular events were partly mediated via CFR. CONCLUSIONS Coronary microvascular dysfunction, but not eGFR, was independently associated with abnormal cardiac mechanics and an increased risk of cardiovascular events. Coronary microvascular dysfunction may mediate the effect of chronic kidney disease on abnormal cardiac function and cardiovascular events in those without overt coronary artery disease.

中文翻译：

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慢性肾功能不全患者的冠状动脉微血管功能障碍，左心室重塑和临床结果。

背景技术在没有明显阻塞性冠状动脉疾病的慢性肾脏疾病患者中，心脏功能障碍和心血管事件普遍存在，但其机制仍知之甚少。冠状动脉微血管功能障碍已被提出为肾功能异常与心脏功能损害和心血管事件之间的联系。我们旨在研究慢性肾脏疾病，冠状动脉微血管功能障碍，心脏功能障碍和不良心血管结果之间的关系。方法纵向对在百翰姆妇女医院接受心脏正电子发射断层扫描，超声心动图和确定肾功能的患者进行研究。患者无明显的冠状动脉（总压力得分<3，无缺血性心脏病的病史），瓣膜，对因器官衰竭和心肌梗死或心力衰竭而死亡或住院的不良综合后果进行随访，并对最终器官疾病进行随访。冠状动脉血流储备（CFR）由正电子发射断层扫描确定。超声心动图用于测量心脏力学：舒张压（外侧和中隔E / e'）和收缩压（整体纵向，径向和周向应变）。图像分析和事件裁决不知情。在调整后的模型和中介分析中评估了估计的肾小球滤过率（eGFR），CFR，舒张和收缩指数与不良心血管结局之间的关联。结果研究的352例患者（中位年龄为65岁；女性为63％；黑人为22％）中，有35％的eGFR <60 mL·min-1·1.73 m-2，左室射血分数中位数为62％， CFR中位数为1.8。eGFR和CFR与舒张和收缩指数以及未来的心血管事件相关（所有P <0.05）。在多变量模型中，CFR（而非eGFR）与心脏力学和心血管事件独立相关。eGFR，心脏力学和心血管事件之间的关联部分通过CFR介导。结论冠状动脉微血管功能障碍（而非eGFR）与心脏力学异常和心血管事件风险增加独立相关。在没有明显冠心病的患者中，冠状动脉微血管功能障碍可能会介导慢性肾脏疾病对心脏功能异常和心血管事件的影响。但eGFR并非独立于心脏力学和心血管事件。eGFR，心脏力学和心血管事件之间的关联部分通过CFR介导。结论冠状动脉微血管功能障碍（而非eGFR）与心脏力学异常和心血管事件风险增加独立相关。在没有明显冠心病的患者中，冠状动脉微血管功能障碍可能会介导慢性肾脏疾病对心脏功能异常和心血管事件的影响。但eGFR并非独立于心脏力学和心血管事件。eGFR，心脏力学和心血管事件之间的关联部分通过CFR介导。结论冠状动脉微血管功能障碍（而非eGFR）与心脏力学异常和心血管事件风险增加独立相关。在没有明显冠心病的患者中，冠状动脉微血管功能障碍可能会介导慢性肾脏疾病对心脏功能异常和心血管事件的影响。与心脏力学异常和心血管事件风险增加独立相关。在没有明显冠心病的患者中，冠状动脉微血管功能障碍可能会介导慢性肾脏疾病对心脏功能异常和心血管事件的影响。与心脏力学异常和心血管事件风险增加独立相关。在没有明显冠心病的患者中，冠状动脉微血管功能障碍可能会介导慢性肾脏疾病对心脏功能异常和心血管事件的影响。