Cardiovascular Risk, Vascular and Kidney Damage in COVID-19 Survivors

COVID-19 幸存者的心血管风险、血管和肾脏损伤

• 批准号: 10553207
• 负责人: JULIO ALONSO CHIRINOS MEDINA
• 金额: $ 79.23万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-20 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10553207
• 关键词: Acceleration; Acute; Admission activity; Albuminuria; Arrhythmia; Arteries; Biological Markers; Blood Vessels; COVID-19; COVID-19 impact; COVID-19 pandemic; COVID-19 survivors; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Characteristics; Chronic; Chronic Kidney Failure; Clinical; Clinical Data; Creatinine; Electronic Health Record; Endothelium; Epidemiology; Event; Exhibits; Femur; Fibrosis; Frequencies; Functional disorder; Future; Glomerular Filtration Rate; Goals; Health; Health system; Heart; Heart Diseases; Heart failure; Hospitalization; Image; Incidence; Infection; Inflammatory; Injury; Intervention; Investigation; Kidney; Kidney Diseases; LCN2 gene; Longitudinal cohort study; Measurement; Measures; Mechanical ventilation; Mediating; Microscopy; Natural History; Organ; Outcome; Outcomes Research; Patients; Peripheral arterial disease; Phenotype; Physicians; Physiologic pulse; Pneumonia; Process; Prospective, cohort study; Public Health; Records; Recovery; Reference Standards; Renal Replacement Therapy; Renal function; Risk; Risk Factors; Risk Reduction; Stress; Stroke; Structure; Survivors; Techniques; Time; Tissues; Tubular formation; Ultrasonography; Update; Vascular Diseases; Vascular Endothelium; Vasoconstrictor Agents; acute coronary syndrome; adjudication; adverse outcome; arterial stiffness; brachial artery; cardiovascular disorder risk; cardiovascular risk factor; cerebrovascular; cohort; community acquired pneumonia; comorbidity; density; elastography; experience; high risk; in vivo; long term consequences of COVID-19; novel; post SARS-CoV-2 infection; post gamma-globulins; post-COVID-19; preventive intervention; prospective; rat KIM-1 protein; renal damage; severe COVID-19; sociodemographics; standard measure; symptomatic COVID-19; thrombotic; urinary

PROJECT SUMMARY The coronavirus disease 2019 (COVID-19) pandemic is a public health crisis, characterized by pneumonia and multiorgan dysfunction. We previously demonstrated that community-acquired pneumonia increases the long- term risk of cardiovascular disease. There is an urgent need to investigate the incidence and mechanisms of cardiovascular disease in COVID-19 survivors. Thus, we propose a novel investigation of the intermediate and long-term cardiac, vascular, and renal consequences of COVID-19. Acutely, COVID-19 is associated with microvascular and macrovascular thrombotic events and inflammatory- and stress-related injury in the heart, kidneys, and vasculature that may put COVID-19 survivors at particularly elevated risk of chronic complications. Our study team has combined expertise in the study of post-pneumonia cardiovascular risk, vascular and kidney pathophysiology, epidemiologic outcomes research, and implementation of longitudinal prospective cohort studies. Our goal is to examine the natural history of cardiac, vascular, and kidney disease in COVID-19 survivors, and to identify risk factors for adverse longitudinal outcomes in these patients. We propose a prospective cohort study evaluating 1) cardiovascular events in a large, electronic health record-based cohort of survivors of COVID-19 in our health system compared with matched controls (“MACE cohort”) and 2) detailed vascular and renal phenotyping in a smaller cohort of COVID- 19 survivors compared with matched controls (“deep phenotyping cohort”). In the MACE cohort, we will collect detailed hospitalization, demographic, and clinical data as well as records for post-COVID-19 hospitalizations. An expert physician panel will prospectively adjudicate hospitalization records to evaluate for post-COVID-19 MACE (heart failure hospitalization, acute coronary syndrome, serious arrhythmia, stroke, peripheral artery disease, and death). In the deep phenotyping cohort, we will perform serial quantitative measurements of vascular health in large, medium-sized, and small arteries, specifically: (1) pulse wave velocity (the reference standard measure of large artery stiffness), (2) flow-mediated dilation (a measure of endothelial function), and (3) microvascular structure assessed by sublingual imaging. We will also perform serial measurements of kidney function (estimated glomerular filtration rate, albuminuria, markers of tubular injury, and exploratory ultrasound images to estimate fibrosis). We aim to assess the long-term incidence of and risk factors for MACE in COVID- 19 survivors, and to evaluate the trajectory of microvascular and macrovascular health and kidney function over time in these patients. Our mechanism-driven approach will provide critical guidance on longitudinal cardiovascular risk and vascular and kidney damage following COVID-19 infection. The results of this study will enhance our understanding of the long-term target organ effects of COVID-19 and identify risk factors that can be targeted by future interventions to ultimately reduce the risk of adverse outcomes in COVID-19 survivors.

项目摘要 2019年冠状病毒病（COVID-19）大流行是一场公共卫生危机，其特征是肺炎， 多器官功能障碍我们以前证明了社区获得性肺炎增加了长- 长期心血管疾病风险。目前迫切需要调查的发病率和机制 新冠肺炎幸存者的心血管疾病。因此，我们提出了一个新的调查的中间体和 COVID-19的长期心脏、血管和肾脏后果。 急性期，COVID-19与微血管和大血管血栓形成事件以及炎症相关- 以及心脏、肾脏和血管系统中与压力相关的损伤，这可能会使COVID-19幸存者特别 慢性并发症的风险增加。我们的研究团队结合了肺炎后研究的专业知识， 心血管风险、血管和肾脏病理生理学、流行病学结局研究，以及 实施纵向前瞻性队列研究。我们的目标是研究心脏病的自然史， 血管和肾脏疾病，并确定不利的纵向风险因素， 这些患者的结果。我们提出了一项前瞻性队列研究，评估1）在一个 我们的卫生系统中基于电子健康记录的COVID-19幸存者队列， 匹配的对照组（“MACE队列”）和2）在较小的COVID-19队列中详细的血管和肾脏表型。 19名幸存者与匹配对照组（“深度表型队列”）进行比较。在MACE队列中，我们将收集 详细的住院、人口统计和临床数据以及COVID-19后住院记录。 一个专家医生小组将前瞻性地裁定住院记录，以评估COVID-19后 MACE（心力衰竭住院、急性冠脉综合征、严重心律失常、卒中、外周动脉 疾病和死亡）。在深度表型队列中，我们将对以下指标进行系列定量测量： 大、中、小动脉的血管健康，具体而言：（1）脉搏波速度（参考 大动脉硬度的标准测量），（2）血流介导的扩张（内皮功能的测量），和 (3)微血管结构通过舌下成像评估。我们还将对肾脏进行系列测量， 功能（估计肾小球滤过率、蛋白尿、肾小管损伤标志物和探查性超声） 估计纤维化的图像）。我们的目标是评估COVID-19中MACE的长期发生率和风险因素， 19名幸存者，并评估微血管和大血管健康和肾功能的轨迹， 这些病人的时间。我们的机制驱动的方法将提供关键的指导，纵向 COVID-19感染后的心血管风险以及血管和肾脏损伤。这项研究的结果将 加强我们对COVID-19的长期靶器官影响的理解，并确定可能 成为未来干预措施的目标，以最终降低COVID-19幸存者的不良后果风险。