Genetic components of exercise tolerance, endothelial and autonomic function and their changes by exercise training in patients with coronary artery disease

Objective: In patients with Coronary Artery Disease (CAD), there is considerable intra-individual variation in peak oxygen uptake (peakVO2), Heart Rate Variability (HRV) and Flow-Mediated Dilatation (FMD), as well as in the response of these phenotypes to physical training. The aim of this study was to identify genetic variants that are associated with these phenotypes and/or with their change after a rehabilitation program, and to determine how much can be explained by these genetic variants. Methodology: We recruited CAD patients who underwent a cardiac rehabilitation program. Exercise testing and the evaluation of endothelial function (assessment of FMD) and of autonomic function (assessment of HRV parameters) were performed prior to and after the rehabilitation program. Genetic Predisposition Scores (GPSs) were generated for each phenotype based on 75 selected Single Nucleotide Polymorphisms (SNPs). Results: At baseline, 260 CAD patients were included in the study. Baseline and follow-up data of peakVO2, HRV and FMD were available for 204 patients. Cardiac rehabilitation increased peakVO2 by 21.7±15.8% (p<0.001), FMD by 36.9±32.6% (p< 0.001) and Total Power (TP) of HRV by 4.7±13.1% (p<0.001). The GPS was an independent predictive variable for all phenotypes at baseline, explaining 9.6% to 11% of the observed variation and 17.6% for the response in peakVO2 after training. Figure 1. GPS for 10 polymorphisms Conclusion: In CAD patients, GPS based on multiple SNPs were strongly associated with peakVO2, FMD, TP of HRV and the response of peakVO2 to training. GPSs explained up to 17.6% of the variance in these phenotypes.