Cardiovascular health assessment & outcomes of systemic lupus erythematosus: bridging pediatric and adult- onset disease

心血管健康评估

• 批准号: 10236519
• 负责人: Joyce Chun-Ling Chang
• 金额: $ 18.43万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10236519
• 关键词: Accounting; Adolescent; Adolescent and Young Adult; Adult; Ambulatory Blood Pressure Monitoring; Antihypertensive Agents; Atherosclerosis; Attenuated; Blood Pressure; Blood Vessels; Cardiac; Cardiology; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Child; Childhood; Chronic; Cox Models; Data; Databases; Development; Disease; Early identification; Electronic Health Record; Endothelium; Etiology; Event; Female Adolescents; Fostering; Future; Glucocorticoids; Goals; Grant; Health; Heart Diseases; Hypertension; Immunosuppression; Infection; Inflammation; Injury; Intervention; Intervention Studies; Knowledge; Longitudinal prospective study; Lupus; Master of Science; Measures; Mediating; Mentors; Methods; Modeling; Monitor; Morbidity - disease rate; Myocardial Infarction; Non-accidental; Obesity; Onset of illness; Outcome Assessment; Outcome Measure; Outcomes Research; Patients; Pattern; Pediatric Hospitals; Pennsylvania; Peripheral; Pharmaceutical Preparations; Pharmacoepidemiology; Pharmacology; Philadelphia; Physiological; Prevention; Recommendation; Renin-Angiotensin System; Reproducibility; Research Personnel; Research Training; Resources; Rheumatism; Rheumatology; Risk; Risk Factors; Risk Marker; Role; Stroke; Systemic Lupus Erythematosus; Testing; Time; Tissues; Training; Universities; Work; arterial tonometry; atheroprotective; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; carotid intima-media thickness; cerebrovascular; clinical epidemiology; cohort; comorbidity; disorder control; endothelial dysfunction; experience; high risk; improved; interdisciplinary collaboration; mortality; multidisciplinary; patient oriented research; premature; premature atherosclerosis; prevent; professor; prospective; recruit; risk stratification; screening; secondary outcome; sex; treatment response; young adult

PROJECT SUMMARY/ABSTRACT Pediatric-onset systemic lupus erythematosus (pSLE) carries a high risk of cardiovascular disease mediated by chronic inflammation and premature atherosclerosis, but responsive surrogate outcome measures of cardiovascular (CV) risk are currently lacking. Loss of nocturnal blood pressure (NBP) decline by ambulatory blood pressure monitoring (ABPM) is common in children with pSLE, and has potential as an early, modifiable, non-invasive measure of vascular health. Loss of NBP decline predicts CV events in adults and may be a marker of endothelial dysfunction, which precedes structural changes in atherosclerosis. More importantly, cardiovascular risk associated with NBP decline is potentially reversible with renin-angiotensin-system (RAS) blockade. In order to determine the role of NBP decline as an outcome measure in pSLE, this proposal seeks to first understand which mechanisms of increased cardiovascular risk contribute to loss of NBP decline, and how NBP decline relates to endothelial function or other measures of subclinical atherosclerosis. Responsive outcome measures would enable studies of interventions to improve vascular health. Potential pharmacologic interventions include RAS blockade, which targets endothelial function without increasing infections from immune suppression. There is, however, a paucity of data to guide the use of RAS blockade in pSLE. The objectives of this proposal are to: 1) identify the major factors that contribute to loss of NBP decline in pSLE; 2) determine whether loss of NBP decline is associated with endothelial dysfunction and could serve as a CV risk marker or potential treatment target; and 3) determine whether RAS blockade is associated with a decreased risk of CV events in adolescents or young adults with SLE. We will perform a prospective longitudinal study of children with SLE recruited to undergo serial ABPM, peripheral endothelial function testing and comprehensive vascular profiles. We will also perform a retrospective analysis using advanced pharmacoepidemiologic methods to estimate the effect of RAS blockade on the risk of cardiovascular events among adolescents and adults in a large electronic health record database. K23 Candidate Dr. Chang completed a Master of Science in Clinical Epidemiology at the University of Pennsylvania (UPenn) and has been appointed as an Assistant Professor at the Children’s Hospital of Philadelphia (CHOP). The proposed research and training plan will provide her with the necessary experience conducting prospective patient-oriented research, expand her expertise in non-invasive vascular assessment and cardiovascular outcomes research, and provide advanced training in pharmacoepidemiologic methods, to become an expert in early identification and prevention of cardiovascular complications of child-onset rheumatic disease. She has established a strong multidisciplinary mentoring team that, together with the vast resources at CHOP and UPenn, will facilitate the proposed work and foster her development as an independent investigator and leader at the cross-section of cardiology and pediatric rheumatology.

项目概要/摘要 儿童发病的系统性红斑狼疮 (pSLE) 具有罹患心血管疾病的高风险 慢性炎症和过早动脉粥样硬化，但反应性替代结果指标 目前缺乏夜间血压（NBP）下降的心血管（CV）风险。 血压监测 (ABPM) 在 pSLE 儿童中很常见，并且有潜力作为早期、可修改的、 血管健康的非侵入性测量 NBP 下降可以预测成人的心血管事件，并且可能是一个 内皮功能障碍的标志，先于动脉粥样硬化的结构变化。 与 NBP 下降相关的心血管风险可能可以通过肾素血管紧张素系统 (RAS) 逆转 为了确定 NBP 下降作为 pSLE 结果测量的作用，该提案寻求 首先了解心血管风险增加的哪些机制导致 NBP 下降的消失，以及 NBP 下降与内皮功能或亚临床动脉粥样硬化反应的其他指标有何关系。 结果测量将使研究能够改善血管健康的潜在药理学。 干预措施包括 RAS 阻断，其目标是内皮功能而不增加感染 然而，缺乏指导 RAS 阻断在 pSLE 中使用的数据。 该提案的目标是：1）确定导致 NBP 下降损失的主要因素 在 pSLE 中；2) 确定 NBP 下降的消失是否与内皮功能障碍相关并且可以发挥作用 作为 CV 风险标记或潜在治疗目标；3) 确定 RAS 阻断是否与 患有系统性红斑狼疮的青少年或年轻人的心血管事件风险降低 我们将进行前瞻性研究。 招募 SLE 儿童进行连续 ABPM、外周内皮功能测试的研究 我们还将使用先进的技术进行回顾性分析。 评估 RAS 阻断对心血管事件风险影响的药物流行病学方法 大型电子健康记录数据库中的青少年和成人。 K23 候选人张博士在英国大学完成了临床流行病学理学硕士学位 宾夕法尼亚大学（宾夕法尼亚大学）并被任命为宾夕法尼亚州儿童医院的助理教授 费城（CHOP）。拟议的研究和培训计划将为她提供必要的经验。 进行前瞻性的以患者为导向的研究，扩大她在无创血管评估方面的专业知识 和心血管结果研究，并提供药物流行病学方法的高级培训，以 成为儿童发病心血管并发症早期识别和预防专家 她建立了一支强大的多学科指导团队，与广大的风湿病患者一起。 CHOP 和 UPenn 的资源将促进拟议的工作并促进她作为一名 心脏病学和儿科风湿病学交叉领域的独立研究者和领导者。