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

心血管健康评估

• 批准号: 10670747
• 负责人: Joyce Chun-Ling Chang
• 金额: $ 17.59万
• 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/10670747
• 关键词: Acceleration; Accounting; Adolescent; Adolescent and Young Adult; Adult; Age; 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; Lupus; Master of Science; Measures; Mediating; Mentors; Methods; Modeling; Monitor; Morbidity - disease rate; Myocardial Infarction; Non-accidental; Obesity; Onset of illness; Outcome; Outcome Measure; Outcomes Research; Patients; Pattern; Pediatric Hospitals; Pennsylvania; Peripheral; Pharmaceutical Preparations; Pharmacoepidemiology; Philadelphia; Physiological; Prevention; Recommendation; Renin-Angiotensin System; Reproducibility; Research; Research Personnel; 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; health assessment; high risk; improved; interdisciplinary collaboration; longitudinal, prospective study; mortality; multidisciplinary; patient oriented research; pharmacologic; 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.

项目摘要/摘要 小儿发作的全身性红斑狼疮（PSLE）具有心血管疾病介导的高风险 通过慢性炎症和早产动脉粥样硬化，但反应迅速的替代结果指标 目前缺乏心血管（简历）风险。夜间血压丧失（NBP）因卧床的下降而下降 血压监测（ABPM）在患有PSLE的儿童中很常见，并且具有早期，可修改的潜力 无创测量血管健康。 NBP下降预测的丧失成人的CV事件，可能是一个 内皮功能障碍的标记，该标志在动脉粥样硬化的结构变化之前。更重要的是， 与NBP下降相关的心血管风险可能与肾素 - 血管紧张素系统（RAS）具有可逆 glocade。为了确定NBP下降作为PSLE中结果度量的作用，该提议寻求 首先了解升高心血管风险的哪些机制导致NBP下降的损失和 NBP如何与内皮功能或亚临床动脉粥样硬化的其他度量有关。响应迅速 结果措施将使干预措施能够改善血管健康。潜在药理 干预措施包括RAS盖胶片，该盖块针对内皮功能而不增加感染 免疫抑制。但是，存在很少的数据来指导在PSLE中使用RAS封锁。 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下降的损失是否与内皮功能障碍有关，并且可以服务 作为简历风险标记或潜在的治疗目标； 3）确定RAS封锁是否与 在青少年或SLE的年轻人中，CV事件的风险降低。我们将执行前瞻性 招募SLE儿童的纵向研究，以经历串行ABPM，周围内皮功能测试 和全面的血管剖面。我们还将使用高级进行回顾性分析 估计RAS封锁对心血管事件风险的影响的药物ePidemiologic方法 在大型电子健康记录数据库中的青少年和成年人中。 K23候选人Chand博士在大学完成了临床流行病学科学硕士学位 宾夕法尼亚州（Upenn），已被任命为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 进行预期的以患者为导向的研究，扩大她在非侵入性血管评估方面的专业知识 和心血管结局研究，并提供药物ePidemiologic方法的高级培训 成为早期识别和预防儿童心血管并发症的专家 风湿病。她已经建立了一个强大的多学科指导团队，该团队与疫苗一起 Chop and Upenn的资源将促进拟议的工作，并促进她的发展 心脏病学和小儿风湿病学横截面的独立研究者和领导者。

项目成果

Racial Disparities in Renal Outcomes Over Time Among Hospitalized Children With Systemic Lupus Erythematosus.

• DOI: 10.1002/art.42127
• 发表时间: 2022-08
• 期刊: ARTHRITIS & RHEUMATOLOGY
• 影响因子: 13.3
• 作者: Chang, Joyce C.;Sears, Cora;Torres, Veronica;Son, Mary Beth F.
• 通讯作者: Son, Mary Beth F.

Opioid use in children with inflammatory bowel disease-related arthritis.

阿片类药物在患有炎症性肠病相关关节炎的儿童中的使用。

• DOI: 10.55563/clinexprheumatol/3bu1sf
• 发表时间: 2023
• 期刊: Clinical and experimental rheumatology
• 影响因子: 3.7
• 作者: BilgicDagci,AtiyeO;Chang,JoyceC;Xiao,Rui;Grossman,AndrewB;Weiss,PamelaF
• 通讯作者: Weiss,PamelaF

Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation.

• DOI: 10.1016/j.kint.2022.04.023
• 发表时间: 2022-08
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Chang, Joyce C.;Weiss, Pamela F.;Xiao, Rui;Atkinson, Meredith A.;Wenderfer, Scott E.
• 通讯作者: Wenderfer, Scott E.

Skewed Cytokine Responses Rather Than the Magnitude of the Cytokine Storm May Drive Cardiac Dysfunction in Multisystem Inflammatory Syndrome in Children.

• DOI: 10.1161/jaha.121.021428
• 发表时间: 2021-08-17
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: Chang JC;Matsubara D;Morgan RW;Diorio C;Nadaraj S;Teachey DT;Bassiri H;Behrens EM;Banerjee A
• 通讯作者: Banerjee A

Longitudinal Assessment of Cardiac Outcomes of Multisystem Inflammatory Syndrome in Children Associated With COVID-19 Infections.

• DOI: 10.1161/jaha.121.023251
• 发表时间: 2022-03
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: Matsubara, Daisuke;Chang, Joyce;Kauffman, Hunter L.;Wang, Yan;Nadaraj, Sumekala;Patel, Chandni;Paridon, Stephen M.;Fogel, Mark A.;Quartermain, Michael D.;Banerjee, Anirban
• 通讯作者: Banerjee, Anirban