Genetics, Fitness, and Left Ventricular Remodelling: The Current State of Play

Cardiorespiratory fitness (CRF) exists on a spectrum and is driven by a constellation of factors, including genetic and environmental differences. This results in wide interindividual variation in baseline CRF and the ability to improve CRF with regular endurance exercise training. As opposed to monogenic conditions, CRF is described as a complex genetic trait as it is believed to be influenced by multiple common genetic variants in addition to exogenous factors. Importantly, CRF is an independent predictor of morbidity and mortality, and so understanding the impact of genetic variation on CRF may provide insights into both human athletic performance and personalized risk assessment and prevention. Despite rapidly advancing technology, progress in this field has been restricted by small sample sizes and the limited number of genetic studies using the "gold standard" objective measure of peak oxygen consumption (VO₂peak) for CRF assessment. In recent years, there has been increasing interest in the heritability of numerous parameters of cardiac structure and function and how this may relate to both normal cardiac physiology and disease pathology. Regular endurance training can result in exercise-induced cardiac remodelling, which manifests as balanced dilation of cardiac chambers and is associated with superior CRF. This results in a complex relationship between CRF, cardiac size, and exercise, and whether shared genetic pathways may influence this remains unknown. In this review we highlight recent and relevant studies into the genomic predictors of CRF with a unique emphasis on how this may relate to cardiac remodelling and human adaptation to endurance exercise.