Clinical Determinants of VO\u3csub\u3e2\u3c/sub\u3e max Response to Endurance Training: HERITAGE Family Study

Background: Maximal oxygen uptake trainability (U+0394VO2max) is largely determined by non-modifiable traits. However, less is known of the contribution of modifiable phenotypes to VO2max response to endurance training. The purpose of this study was to examine the relationship between baseline cardiopulmonary, metabolic, and body composition traits and U+0394VO2max. Methods: Subjects were 717 healthy, physically inactive adults (44% female, 34% Black) who completed a 20-week, highly standardized, endurance training program as part of the HERITAGE Family Study. Resting and exercise phenotypes were collected at baseline and post-training. A total of 33 variables related to cardiopulmonary, metabolic, and body composition phenotypes were entered into a forward selection model with U+0394VO2maxabs (mL/min) as the dependent variable. Alternative U+0394VO2max outcome regression models were performed across the study sample, including models with change in relative (mL/kg/min) and percent change in absolute and relative VO2max. Models were then stratified by race and sex. The frequency of significant phenotypes was summed across all models. A baseline signature of U+0394VO2maxabs was explored using a LASSO penalized regression model with a total of 102 variables. Results: The final model revealed 10 baseline traits significantly (p2maxabs. Submaximal cardiopulmonary phenotypes showed positive (e.g., cardiac output at 50 W) and negative (e.g., stroke volume index, arteriovenous oxygen difference at 50 W) associations with U+0394VO2maxabs. Body composition traits were also positively (e.g., fat free mass) and negatively (e.g., abdominal visceral fat) associated with U+0394VO2maxabs. Resting lactate concentration was negatively associated with U+0394VO2maxabs. Body composition and metabolic phenotypes were consistently significant in Black and male subjects. Submaximal cardiopulmonary phenotypes were mostly significant in White and female subjects. The baseline signature of U+0394VO2maxabs was comprised of submaximal cardiac output and fat free mass. Conclusion: Intrinsic values of body composition, resting lactate, and submaximal cardiopulmonary phenotypes may represent targets to maximize the cardiorespiratory fitness benefits of regular endurance exercise. Further research is needed to examine the influence of these traits on U+0394VO2max across varying exercise types and doses