Aortic Dilatation in Endurance Athletes: A Physiologic and Mechanistic Study

耐力运动员的主动脉扩张：生理学和机制研究

• 批准号: 10681473
• 负责人: Timothy CHURCHILL
• 金额: $ 19.66万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10681473
• 关键词: Acute; Age; Aorta; Aortic Diseases; Area; Arteries; Biochemical; Biological Markers; Biology; Blood Pressure; Blood Vessels; Blood flow; Body Size; Caliber; Cardiac; Cardiopulmonary; Cardiovascular system; Chronic; Clinical Investigator; Complement; Dangerousness; Data; Development Plans; Dilatation - action; Dose; Echocardiography; Enrollment; Environment; Equilibrium; Evaluation; Exercise; Exercise Physiology; Exercise Test; Exertion; Functional disorder; Future; General Hospitals; General Population; Genetic; Goals; Grant; Growth; Health; Human; Hypertension; Image; Individual; Isometric Exercise; Isotonic Exercise; Maps; Massachusetts; Mediator; Mentored Patient-Oriented Research Career Development Award; Mentorship; MicroRNAs; Mission; Modeling; Molecular; Myocardial; Natural History; Organ; Pathologic; Pathology; Patients; Pattern; Performance; Persons; Phenotype; Physical activity; Physiological; Physiology; Plasma; Play; Population; Positioning Attribute; Prevalence; Process; Publications; Regulation; Research; Research Methodology; Research Proposals; Rest; Risk; Risk Factors; Role; Sampling; Science; Scientist; Sports; Strenuous Exercise; Structure; Surveys; Syndrome; Techniques; Testing; Time; Tissues; Training; Translating; Translational Research; Uncertainty; Validation; Veterans; Work; X-Ray Computed Tomography; aged; anatomic imaging; ascending aorta; career; career development; circulating microRNA; clinical outcome assessment; clinical practice; cohort; comparative; comparison group; endurance exercise; exercise training; experience; follow-up; heart imaging; high risk population; indexing; insight; male; multidisciplinary; next generation sequencing; novel; primary outcome; programs; prospective; response; sedentary; sex; transcriptome sequencing; translational scientist; translational study

PROJECT SUMMARY / ABSTRACT The candidate recently joined the staff at Massachusetts General Hospital (MGH) in the Cardiovascular Performance Program (CPP), a unique group whose goals include conducting top-caliber human health and performance research. A core mission of the CPP is to use endurance athletes as a model through which to study the impacts of exercise on the cardiovascular system. This proposal applies this framework to evaluate in detail on the impact of exercise on the aorta. This proposal emerged from the dual observations that a) myocardial adaptation to exercise training is a well-established process that is felt to be adaptive rather than pathologic, while plasticity of the aorta has not been documented, and b) endurance athletes with aortic enlargement are commonly encountered in clinical practice. The candidate accordingly performed an initial study enrolling ~450 athletes and documenting an elevated prevalence of aortic dilatation in this population as compared to established population norms. This research proposal aims to define natural history, underlying physiology, and potential mechanisms underlying this phenotype of aortic dilation in endurance athletes, with the overarching goal of helping to establish whether this may represent an exercise-associated adaptation vs a novel form of overuse pathology. To achieve these goals, the applicant proposes to build off his prior work, leveraging the large cohort of athletes whom he enrolled into the initial study. Longitudinal follow-up will be performed on athlete subjects using echocardiography to mirror the index assessment. A subset will undergo detailed comparative physiologic phenotyping with cardiopulmonary exercise testing, advanced echocardiographic techniques including non-invasive evaluation of intracardiac and aortic blood flow patterns, vascular function profiling, and detailed anatomic imaging with computed tomography. Where possible, testing will be performed at rest and in response to physiologic provocation. Phenotypic profiles will be compared across athletes with and without aortic dilatation and control subjects with aortic dilatation to assess physiologic differences and potential mechanisms. Molecular evaluation will focus on plasma microRNA (miRNA), a class of molecules with well- established exercise responsiveness and known mechanistic associations with aortic disease, and circulating miRNA profiles will be assessed across these groups before and after exercise. The candidate’s career development plan includes advanced training in exercise physiology, cardiac imaging and physiologic phenotyping, translational science, and research methodology, all under the mentorship of a unique multidisciplinary team. The proposed science science will set the stage for future studies to assess clinical outcomes in this population and integrate additional translational study of exercise- associated aortic disease, which will form the basis of the candidate’s future R01 proposals. Over the course of the K23 award, the candidate’s goal is to develop into an independent clinical and translational investigator.

项目摘要/摘要

项目成果

Rationale and Design of the ORCCA (Outcomes Registry for Cardiac Conditions in Athletes) Study.

• DOI: 10.1161/jaha.122.029052
• 发表时间: 2023-06-06
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4

Risk tolerance and eligibility decision-making strategies among young competitive athletes: novel insights into the emerging practice of shared decision making.

年轻竞技运动员的风险承受能力和资格决策策略：对共同决策新兴实践的新见解。

• DOI: 10.1093/eurjpc/zwad250
• 发表时间: 2024
• 期刊: European journal of preventive cardiology
• 影响因子: 8.3
• 作者: Churchill,TimothyW;O'Kelly,AnnaC;Montembeau,SarahC;Kim,JonathanH;Guseh,JamesS;Wasfy,MeaganM;Dickert,NealW;Baggish,AaronL
• 通讯作者: Baggish,AaronL

Echocardiographic Reporting of the Aorta in Young Competitive Athletes.

年轻竞技运动员主动脉的超声心动图报告。

• DOI: 10.1016/j.echo.2022.11.004
• 发表时间: 2023
• 期刊: Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography
• 作者: Petek,BradleyJ;Moulson,Nathaniel;Klein,ChristianF;Drezner,JonathanA;Harmon,KimberlyG;Kliethermes,StephanieA;Patel,ManeshR;Isselbacher,EricM;Baggish,AaronL;Churchill,TimothyW
• 通讯作者: Churchill,TimothyW

Consumer Wearable Health and Fitness Technology in Cardiovascular Medicine: JACC State-of-the-Art Review.

心血管医学中的消费者可穿戴健康和健身技术：JACC 最先进的评论。

• DOI: 10.1016/j.jacc.2023.04.054
• 发表时间: 2023
• 期刊: Journal of the American College of Cardiology
• 影响因子: 24
• 作者: Petek,BradleyJ;Al-Alusi,MostafaA;Moulson,Nathaniel;Grant,AubreyJ;Besson,Cyril;Guseh,JSawalla;Wasfy,MeaganM;Gremeaux,Vincent;Churchill,TimothyW;Baggish,AaronL
• 通讯作者: Baggish,AaronL