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

Abstract

Cardiorespiratory fitness (CRF) exists on a spectrum and is driven by a constellation of factors including genetic and environmental differences. This results in wide inter-individual 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 therefore understanding the impact of genetic variation on CRF may provide insights into both human athletic performance and also personalised 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 utilizing 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 might relate to both normal cardiac physiology and disease pathology. Regular endurance training can result in exercise-induced cardiac remodeling 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. This review will highlight recent and relevant studies in to the genomic predictors of CRF with a unique emphasis on how this may relate to cardiac remodeling and human adaption to endurance exercise.