Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, Atlanta, GA.
Cardiovascular Performance Program, Massachusetts General Hospital, Boston MA.
Med Sci Sports Exerc. 2022 Oct 1;54(10):1617-1624. doi: 10.1249/MSS.0000000000002960. Epub 2022 May 26.
Metabolomics identifies molecular products produced in response to numerous stimuli, including both adaptive (includes exercise training) and disease processes. We analyzed a longitudinal cohort of American-style football (ASF) athletes, who reliably acquire maladaptive cardiovascular (CV) phenotypes during competitive training, with high-resolution metabolomics to determine whether metabolomics can discriminate exercise-induced CV adaptations from early CV pathology.
Matched discovery ( n = 42) and validation ( n = 40) multicenter cohorts of collegiate freshman ASF athletes were studied with longitudinal echocardiography, applanation tonometry, and high-resolution metabolomics. Liquid chromatography-mass spectrometry identified metabolites that changed ( P < 0.05, false discovery rate <0.2) over the season. Metabolites demonstrating similar changes in both cohorts were further analyzed in linear and mixed-effects models to identify those associated with left ventricular mass, tissue-Doppler myocardial E ' velocity (diastolic function), and arterial function (pulse wave velocity).
In both cohorts, 20 common metabolites changed similarly across the season. Metabolites reflective of favorable CV health included an increase in arginine and decreases in hypoxanthine and saturated fatty acids (heptadecanoate, arachidic acid, stearate, and hydroxydecanoate). In contrast, metabolic perturbations of increased lysine and pipecolate, reflective of adverse CV health, were also observed. Adjusting for player position, race, height, and changes in systolic blood pressure, weight, and pulse wave velocity, increased lysine ( β = 0.018, P = 0.02) and pipecolate ( β = 0.018, P = 0.02) were associated with increased left ventricular mass index. In addition, increased lysine ( β = -0.049, P = 0.01) and pipecolate ( β = -0.052, P = 0.008) were also associated with lower E ' (reduced diastolic function).
ASF athletes seem to develop metabolomic changes reflective of both favorable CV health and early CV maladaptive phenotypes. Whether metabolomics can discriminate early pathologic CV transformations among athletes is a warranted future research direction.
代谢组学可识别出对多种刺激（包括适应性（包括运动训练）和疾病过程）产生的分子产物。我们分析了一个美式足球（ASF）运动员的纵向队列，这些运动员在竞技训练中可靠地获得了适应性不良的心血管（CV）表型，采用高分辨率代谢组学来确定代谢组学是否可以区分运动引起的 CV 适应性与早期 CV 病理学。
对大学新生 ASF 运动员的匹配发现（n = 42）和验证（n = 40）多中心队列进行了研究，包括纵向超声心动图、平板张力测量和高分辨率代谢组学。液相色谱-质谱鉴定出季节性变化（P < 0.05，错误发现率<0.2）的代谢物。在两个队列中表现出相似变化的代谢物进一步通过线性和混合效应模型进行分析，以确定与左心室质量、组织多普勒心肌 E '速度（舒张功能）和动脉功能（脉搏波速度）相关的代谢物。
在两个队列中，有 20 种常见代谢物在整个季节表现出相似的变化。反映 CV 健康状况良好的代谢物包括精氨酸增加和次黄嘌呤以及饱和脂肪酸（十七烷酸、花生酸、硬脂酸和羟基癸酸）减少。相反，还观察到代谢物中赖氨酸和哌可酸盐的增加，这反映了 CV 健康状况不佳。在调整运动员位置、种族、身高以及收缩压、体重和脉搏波速度变化后，赖氨酸（β=0.018，P=0.02）和哌可酸盐（β=0.018，P=0.02）与左心室质量指数增加相关。此外，赖氨酸（β=-0.049，P=0.01）和哌可酸盐（β=-0.052，P=0.008）的增加也与 E '降低（舒张功能降低）相关。
ASF 运动员似乎会产生反映 CV 健康状况良好和早期 CV 适应性不良表型的代谢组学变化。代谢组学是否可以区分运动员的早期病理 CV 转化是一个值得未来研究的方向。
