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:
    9513611
  • 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:
    2017-09-01 至 2022-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT___________________________________________________________ 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.
项目总结/摘要_ 目前评估心血管疾病(CVD)风险的方法主要基于以下评估: 静息状态下,但人体循环和代谢进化到对生理应激作出反应。全身 对运动引起的扰动的反应可能携带关于心血管疾病的关键预后信息。 健康和储备能力。特别是心肺功能受损,代表低峰值氧 摄取是跨风险分层的CVD结果的有效预测因子。然而,在多大程度上受损 心肺适能对不同代谢途径紊乱的影响尚不清楚。 此应用程序将结合联合收割机两个国家的最先进的技术-先进的心肺运动测试 采用综合气体交换措施和~290循环高通量剖面的CPET 代谢物(在休息和高峰运动时测量)-深入表型代谢反应, 增量练习。我们推测,受损的心肺功能与离散的代谢产物 特征,这些代谢物特征与普遍的亚临床CVD特征和偶发CVD有关 结果,并且这些签名通过有氧运动训练进行修改。在目标1中,我们将评估 在社区招募的3040名参与者中, 心脏病研究中心。我们还将分析这些代谢物特征与临床的关系。 风险因素,新的风险标志物,亚临床疾病的措施,和运动相关的偏移,在选择 途径生物标志物。在目标2中,我们将研究这些代谢物特征与CVD事件的关系 和代谢综合征,以及1040例CVD住院和死亡 患者在医院转诊队列中。在目标3中,我们将研究有氧运动训练的效果 心肺适能受损和CPET气体交换代谢物特征的纵向变化 变量在三个不同的和临床相关的医院为基础的样本(总N=60)。的首要目标 这项建议是为了评估运动的代谢反应提供增量的前提, 关于从心脏代谢风险因素转变为明显CVD的信息。这项研究将是 完成了一个全面的职业发展计划,旨在提供博士设置。 一个早期的职业调查员和心脏病专家,拥有成为一名独立医生所需的技能, 心血管医学的科学家他的长期职业目标是利用生理学的深入表征 运动反应,以确定早期CVD表型,这将进一步了解疾病 发病机制,并能够发现新的预防目标。一个优秀的指导团队和一个 运动生理学、代谢物分析和 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 在授标期间保持独立性。

项目成果

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科研奖励数量(0)
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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:
    10459683
  • 财政年份:
    2017
  • 资助金额:
    $ 19.98万
  • 项目类别:

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