Comprehensive Metabolic Profiling of Exercise to Predict Cardiometabolic Risk

运动的综合代谢分析可预测心脏代谢风险

基本信息

批准号：
9038045
负责人：
Gregory Dyer Lewis
金额：
$ 49.08万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2019-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9038045
关键词：
Accelerometer Adult Age Attention Blood Blood Pressure Blood Vessels Calcium Cardiopulmonary Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Case-Control Studies Cessation of life Chronic Disease Citric Acid Cycle Clinical Communities Complex Coronary artery Diabetes Mellitus Disease Disease Outcome Environmental air flow Exercise Exercise stress test Exposure to Framingham Heart Study Functional disorder Future Gases General Population Generations Genetic Variation Glycolysis Health Heart Heart Rate Human Individual Intervention Kinetics Left Ventricular Hypertrophy Life Style Lipolysis Measurement Measures Medical Genetics Metabolic Metabolic Diseases Minority Myocardial Infarction Niacinamide Obesity Organ Outcome Oxygen Pantothenic Acid Patients Pattern Performance Persons Phenotype Physical activity Physiological Population Quality of life Recording of previous events Reporting Rest Risk Factors Sampling Speed Staging Technology Testing United States Whole Organism arterial stiffness base cardiometabolic risk cardiorespiratory fitness cardiovascular disorder risk cardiovascular health cardiovascular risk factor clinical practice cohort cost exercise capacity fatty acid oxidation fitness glycogenolysis high risk improved insulin sensitivity metabolic phenotype metabolic profile metabolomics middle age minimally invasive mortality outcome forecast population based prevent prognostic prognostic significance prognostic value public health relevance response trait uptake ventricular hypertrophy

项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is responsible for one third of all deaths in the United States, with the estimated costs anticipated to increase from $500 billion to $1,200 billion between 2015 and 2030. Given the societal burden of CVD, considerable attention has been directed at major risk factors for CVD. Recognition, understanding and widespread ascertainment of additional actionable CVD risk factors is necessary. Greater exercise capacity (e.g. cardiorespiratory fitness) is increasingly recognized to decrease the burden of chronic diseases, promote cardiovascular health, improve quality of life, and delay CVD and mortality. Although fitness has been shown to be among the most potent predictors of future CVD and overall health outcomes, it is currently one of the only major risk factors that is not routinely and regularly assessed in either general or specialized clinical settings. Beyond permitting quantification of fitness, brief (~10min) exposure to exercise can also unmask early forms of CVD. We and others have shown that simple measurements of heart rate and blood pressure during exercise in population studies are of incremental prognostic value over the same measurements made at rest. Recent technological advances now permit measurement of a broad array of circulating metabolites and gas exchange patterns that reflect the complex metabolic responses to exercise. The central hypothesis of this proposal is that precise measurements of metabolic responses to exercise through cardiopulmonary exercise testing (CPET) combined with metabolite profiling during exercise will relate to clinical and genetic traits as well as subclinical CVD, and will be of incremental value beyond standard CV risk factor assessment (in the resting state) for predicting future CVD and cardiometabolic disease. Aim 1 will comprehensively determine how standard risk factors, life-style measures (including precise accelerometry-based physical activity measures), genetic variation and familial traits relate to metabolic responses to exercise, as measured by changes in gas exchange variables and metabolite levels in response to incremental exercise. Aim 2 will determine how previously ascertained subclinical disease measures (conduit artery stiffness, coronary artery calcium, ventricular hypertrophy) relate to metabolic responses to exercise. Aim 3 will determine whether easily acquired CPET gas exchange variables and changes in circulating metabolites in response to exercise will incrementally predict future cardiometabolic and CVD outcomes in the Framingham Heart Study and in a separate referral cohort. Overall, our proposal will help identify and characterize the spectrum of metabolic changes during exercise in the community, and assess their cross-sectional correlates and long-term prognostic significance. We hope to identify a minimally invasive means to test CV and metabolic reserve capacity that will identify and refine risk factors that can be targeted for interventions to prevet CVD.

描述（由适用提供）：心血管疾病（CVD）负责美国所有死亡人数的三分之一，预计预计将从2015年至2030年间增加到2015年至2030年之间的12000亿美元。鉴于CVD的社交伯恩（CVD）的社交伯恩（CVD）已引起了CVD的主要风险因素。识别，理解和广泛确定额外可行的CVD风险因素的确定性是，尽管已证明健身是未来CVD和整体健康状况的最潜在预测指标之一，但目前，它是唯一不常规且不定期评估的主要危险因素之一设置。除了允许量化健身之外，短暂的（〜10分钟）接触运动也可以揭示CVD的早期形式。我们和其他人表明，在静止时进行的相同测量值中，在人群研究中，在运动过程中对心率和血压的简单测量具有渐进性的预后价值。现在的技术进步现在允许测量各种循环代谢物和气体交换模式，这些代谢方式反映了复杂的代谢反应。该提案的中心假设是，通过心肺运动测试（CPET）与锻炼过程中的代谢物分析相结合的代谢反应的精确测量将与临床和遗传性状以及亚临床CVD有关，以及亚临床CVD以及超出标准的CV风险因素评估和预测未来CV的标准危险因素超出标准的CV风险因素。 AIM 1 AIM 2将决定标准风险因素，生命式测量值（包括基于加速度计的体育活动测量值），遗传变异和家庭特征与对运动的代谢反应有关，这是通过气体交换变量的变化以及对渐进运动的响应中的代谢水平来衡量的。 AIM 2将确定先前确定的亚临床疾病措施（导管动脉刚度，冠状动脉钙，心室肥大）与运动的代谢反应有关。 AIM 3将确定在Framingham Heart研究中以及在单独的推荐人群中，是否可以轻松获得的CPET气体交换变量和循环代谢物的变化是否会逐步预测未来的心脏代谢和CVD结果。总体而言，我们的建议将有助于确定和表征社区运动过程中代谢变化的范围，并评估其横断面相关性和长期预后意义。我们希望确定测试简历和代谢储备能力的最低侵入性手段，该手段将识别并完善可以针对干预措施的危险因素进行预先prevet CVD。