Metabolic Signatures of Impaired Cardiorespiratory Fitness: Correlates, Prognostic Significance and Modulation with Exercise Training
心肺健康受损的代谢特征:相关性、预后意义以及运动训练的调节
基本信息
- 批准号:10459683
- 负责人:
- 金额:$ 19.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-07-01 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccelerometerAdvisory CommitteesAerobicAerobic ExerciseAffectAgeAwardBiological MarkersBiostatistical MethodsBloodBlood CirculationBody CompositionCardiac Surgery proceduresCardiac rehabilitationCardiometabolic DiseaseCardiopulmonaryCardiovascular DiseasesCardiovascular systemCessation of lifeClinicalCommunitiesDataDevelopmentDiseaseDisease OutcomeDual-Energy X-Ray AbsorptiometryEchocardiographyEmployeeEnrollmentEpidemiologic MethodsExerciseExercise PhysiologyExercise TestFoundationsFramingham Heart StudyFutureGasesGoalsHand StrengthHeartHeart failureHospitalizationHospitalsHumanImpairmentIncidenceIndividualLungMeasuresMedicineMentorsMetabolicMetabolic PathwayMetabolic syndromeMetabolismMethodsOxygenParticipantPathogenesisPathway interactionsPatientsPhenotypePhysical ExercisePhysical activityPhysiciansPhysiologicalPopulationPreventionProgram DevelopmentResearchResearch PersonnelResourcesRestRiskRisk FactorsRisk MarkerSamplingSampling StudiesScientistStandardizationStressStrokeSupervisionTechniquesTestingTimeTrainingbasecardiometabolic riskcardiometabolismcardiorespiratory fitnesscardiovascular disorder riskcardiovascular healthcareercareer developmentclinical riskclinically relevantcohortdesigndisease phenotypeexercise programexercise trainingfitnessheart disease riskimprovedinsightmetabolic phenotypemortalitynovelprognosticprognostic significanceresponserisk predictionsedentarysexskillssmall moleculetonometrytraittranslational physiciantranslational scientistuptake
项目摘要
Current methods to evaluate cardiovascular disease (CVD) risk are primarily based on assessments made in
the resting state, but human circulation and metabolism evolved to respond to physiologic stress. The systemic
response to exercise-induced perturbations may carry key prognostic information regarding cardiovascular
health and reserve capacity. In particular, impaired cardiorespiratory fitness, representing low peak oxygen
uptake, is a potent predictor of CVD outcomes across strata of risk. However, the extent to which impaired
cardiorespiratory fitness reciprocally influences derangements in distinct metabolic pathways remains unclear.
This application will combine two state-of-the-art techniques – advanced cardiopulmonary exercise testing
(CPET) with comprehensive gas exchange measures and high-throughput profiling of ~290 circulating
metabolites (measured at rest and peak exercise) – to deeply phenotype the metabolic responses to
incremental exercise. We postulate that impaired cardiorespiratory fitness associates with discrete metabolite
signatures, that these metabolite signatures relate to prevalent subclinical CVD traits and incident CVD
outcomes, and that these signatures are modified by aerobic exercise training. In Aim 1, we will evaluate the
metabolite signatures of impaired cardiorespiratory fitness in 3040 participants enrolled in the community-
based Framingham Heart Study. We will also analyze the relations of these metabolite signatures to clinical
risk factors, novel risk markers, subclinical disease measures, and exercise-related excursions in select
pathway biomarkers. In Aim 2, we will examine the relations of these metabolite signatures to incident CVD
and metabolic syndrome in the Framingham Heart Study, and to CVD hospitalization and death in 1040
patients in a hospital-based referral cohort. In Aim 3, we will investigate the effect of aerobic exercise training
on longitudinal changes in metabolite signatures of impaired cardiorespiratory fitness and CPET gas exchange
variables in three distinct and clinically relevant hospital-based samples (total N=60). The overarching goal of
this proposal is to evaluate the premise that the metabolic responses to exercise provide incremental
information regarding the transition from cardiometabolic risk factors to overt CVD. This research will be
accomplished in the setting of a comprehensive career development program designed to provide Dr. Nayor,
an early career investigator and cardiologist, with the skills needed to become an independent physician-
scientist in cardiovascular medicine. His long-term career goal is to use in-depth characterization of physiologic
exercise responses to identify early CVD phenotypes that will further our understanding of disease
pathogenesis and enable discovery of novel targets for prevention. An outstanding mentoring team and an
advisory committee of established scientists in the fields of exercise physiology, metabolite profiling, and
advanced epidemiological and biostatistical methods will guide the candidate in his transition to scientific
independence over the course of the award period.
目前评估心血管疾病(CVD)风险的方法主要基于
静息状态,但人类的循环和新陈代谢是为了对生理应激做出反应而进化的。系统性的
对运动诱导的干扰的反应可能携带有关心血管疾病的关键预后信息
健康和储备能力。尤其是心肺功能受损,表现为低峰氧量
摄取率,是不同风险层次心血管疾病结局的有力预测指标。然而,损害的程度
心肺健康对不同代谢途径的紊乱有相互影响的作用尚不清楚。
这项应用将结合两项最先进的技术-先进的心肺运动测试
(CPET)具有全面的气体交换措施和高通量~290循环剖面图
代谢物(在休息和高峰运动时测量)--对代谢反应的深入表型
渐进式运动。我们推测心肺功能受损与离散代谢物有关。
这些代谢物特征与流行的亚临床心血管疾病特征和事件心血管疾病有关
结果,这些特征可以通过有氧运动训练来改变。在目标1中,我们将评估
社区登记的3040名参与者心肺功能受损的代谢物特征
以弗雷明翰心脏研究为基础。我们还将分析这些代谢物特征与临床的关系。
选择的风险因素、新的风险标记物、亚临床疾病测量和运动相关的短途旅行
途径生物标记物。在目标2中,我们将检查这些代谢物特征与心血管事件的关系
弗雷明翰心脏研究中的代谢综合征,以及1040年心血管疾病住院和死亡
以医院为基础的转诊队列中的患者。在目标3中,我们将调查有氧运动训练的效果
心肺功能和CPET气体交换受损代谢物特征的纵向变化
在三个不同的和临床相关的医院样本中的变量(总计N=60)。的首要目标是
这项建议是为了评估这样一个前提,即运动的代谢反应提供了增量
关于心脏代谢危险因素向显性心血管疾病转变的信息。这项研究将是
在一个全面的职业发展计划的背景下完成,旨在为Nayor博士提供
职业生涯早期的调查员和心脏病专家,具备成为一名独立医生所需的技能-
心血管内科科学家。他的长期职业目标是利用生理学的深入刻画
识别早期心血管疾病表型的运动反应将加深我们对疾病的理解
并能够发现新的预防靶点。一支优秀的指导团队和
运动生理学、代谢物分析和研究领域的知名科学家顾问委员会
先进的流行病学和生物统计学方法将指导候选人过渡到科学
在获奖期内保持独立性。
项目成果
期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Molecular Aspects of Lifestyle and Environmental Effects in Patients With Diabetes: JACC Focus Seminar.
糖尿病患者生活方式和环境影响的分子方面:JACC 焦点研讨会。
- DOI:10.1016/j.jacc.2021.02.070
- 发表时间:2021
- 期刊:
- 影响因子:24
- 作者:Nayor,Matthew;Shah,SvatiH;Murthy,Venkatesh;Shah,RaviV
- 通讯作者:Shah,RaviV
Feasibility, Methodology, and Interpretation of Broad-Scale Assessment of Cardiorespiratory Fitness in a Large Community-Based Sample.
- DOI:10.1016/j.amjcard.2021.07.020
- 发表时间:2021-10-15
- 期刊:
- 影响因子:2.8
- 作者:Nayor, Matthew;Shah, Ravi, V;Tanguay, Melissa;Blodgett, Jasmine B.;Chernofsky, Ariel;Miller, Patricia E.;Xanthakis, Vanessa;Malhotra, Rajeev;Houstis, Nicholas E.;Velagaleti, Raghava S.;Larson, Martin G.;Vasan, Ramachandran S.;Lewis, Gregory D.
- 通讯作者:Lewis, Gregory D.
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Matthew G. Nayor其他文献
Association of Systemic Thromboxane Generation With Risk of Developing Heart Failure
全身性血栓烷生成与心力衰竭发生风险的关联
- DOI:
10.1016/j.jacc.2024.09.010 - 发表时间:
2025-01-07 - 期刊:
- 影响因子:22.300
- 作者:
Jeffrey J. Rade;Shari S. Kronsberg;Thomas S. Kickler;Ramachandran S. Vasan;Vanessa Xanthakis;Matthew G. Nayor;Bruce A. Barton - 通讯作者:
Bruce A. Barton
DIAGNOSING HFPEF: VALIDATION OF A NONINVASIVE DIAGNOSTIC APPROACH AGAINST INVASIVE HEMODYNAMICS
- DOI:
10.1016/s0735-1097(20)31538-2 - 发表时间:
2020-03-24 - 期刊:
- 影响因子:
- 作者:
Shawn X. Li;Timothy W. Churchill;Lisa A. Curreri;Elizabeth Liu;Robyn Farrell;Mark W. Schoenike;John Sbarbaro;Jennifer N. Rouvina;Casey G. White;Alyssa Kowal;Rajeev Malhotra;Matthew G. Nayor;Gregory D. Lewis;Jennifer E. Ho - 通讯作者:
Jennifer E. Ho
Matthew G. Nayor的其他文献
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{{ truncateString('Matthew G. Nayor', 18)}}的其他基金
Metabolic Responses to an Oral Mixed Meal Tolerance Test: Intra-individual changes, correlates, and prognostic significance
口服混合膳食耐受性测试的代谢反应:个体内变化、相关性和预后意义
- 批准号:
10178458 - 财政年份:2021
- 资助金额:
$ 19.98万 - 项目类别:
Metabolic Responses to an Oral Mixed Meal Tolerance Test: Intra-individual changes, correlates, and prognostic significance
口服混合膳食耐受性测试的代谢反应:个体内变化、相关性和预后意义
- 批准号:
10665035 - 财政年份:2021
- 资助金额:
$ 19.98万 - 项目类别:
Metabolic Responses to an Oral Mixed Meal Tolerance Test: Intra-individual changes, correlates, and prognostic significance
口服混合膳食耐受性测试的代谢反应:个体内变化、相关性和预后意义
- 批准号:
10471798 - 财政年份:2021
- 资助金额:
$ 19.98万 - 项目类别:
Metabolic Signatures of Impaired Cardiorespiratory Fitness: Correlates, Prognostic Significance and Modulation with Exercise Training
心肺健康受损的代谢特征:相关性、预后意义以及运动训练的调节
- 批准号:
9513611 - 财政年份:2017
- 资助金额:
$ 19.98万 - 项目类别:
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