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

• 批准号: 9197327
• 负责人: Gregory Dyer Lewis
• 金额: $ 55.76万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 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/9197327
• 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; Population Study; Quality of life; Recording of previous events; Reporting; Rest; Risk Factors; Sampling; Speed; 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; prospective; public health relevance; response; trait; uptake; ventricular hypertrophy

 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（由申请人提供）：心血管疾病（CVD）占美国所有死亡人数的三分之一，预计在2015年至2030年期间，估计费用将从5000亿美元增加到12000亿美元。鉴于CVD的社会负担，相当多的注意力已经指向CVD的主要风险因素。识别、理解和广泛查明其他可采取行动的CVD风险因素是必要的。越来越多的人认识到，更大的运动能力（例如心肺健康）可以减轻慢性疾病的负担，促进心血管健康，改善生活质量，并延迟CVD和死亡率。虽然健身已被证明是未来心血管疾病和整体健康结果的最有力的预测因素之一，但它是目前唯一的主要风险因素之一，在一般或专业临床研究中没有常规和定期评估。 设置. 除了允许量化健身之外，短暂（约10分钟）的运动也可以揭示CVD的早期形式。我们和其他人已经表明，在人群研究中，运动时简单测量心率和血压比在休息时进行的相同测量具有更高的预后价值。最近的技术进步现在允许测量广泛的循环代谢物和气体交换模式，反映了运动的复杂代谢反应。该提案的中心假设是，通过心肺运动试验（CPET）结合运动期间代谢产物分析对运动代谢反应的精确测量将与临床和遗传特征以及亚临床CVD相关，并且将具有超出标准CV风险因素评估（静息状态）的增量价值，用于预测未来的CVD和心脏代谢疾病。目标1将全面确定标准风险因素，生活方式措施（包括精确的基于加速度计的体力活动措施），遗传变异和家族特征与运动代谢反应的关系，通过气体交换变量和代谢物水平的变化来测量。目标2将确定以前确定的亚临床疾病指标（导管动脉僵硬度，冠状动脉钙，心室肥大）与运动代谢反应的关系。目标3将确定是否容易获得的CPET气体交换变量和循环代谢物的变化，以响应运动将增量预测未来的心脏代谢和心血管疾病的结果在心脏研究和一个单独的转诊队列。总的来说，我们的建议将有助于确定和表征社区运动期间代谢变化的谱，并评估其横截面相关性和长期预后意义。我们希望确定一种微创方法来测试CV和代谢储备能力，以确定和改进可用于干预CVD的风险因素。