Sex-specific improvement in cardiac phenotype in older females combining blood withdrawal and exercise training.

This study determined whether an intervention combining hematological and exercise stimuli may overcome the prevailing limitations to improve the cardiac phenotype and orthostatic tolerance (OT) of females with advanced age. Healthy females ( = 15) and males ( = 14) matched by age (63.7 ± 7.0 vs. 63.6 ± 8.7 yr) and moderate physical activity were recruited. OT, transthoracic echocardiography, and central hemodynamics were assessed during incremental lower body negative pressure (LBNP) levels (up to -50 mmHg) for 1 h or until presyncope, prior to and after an intervention comprising standard (10%) blood withdrawal and an 8-wk exercise training program designed to maximize central hemodynamic adaptations. OT time was lower in females compared with males (48.1 ± 10.6 vs. 57.0 ± 4.8 min, = 0.008) before the intervention. Improved OT time (+11%) in females (48.1 ± 10.6 vs. 53.5 ± 6.1 min, = 0.021) but not in males (57.0 ± 4.8 vs. 56.7 ± 5.6 min, = 0.868) was found following the intervention, resulting in similar OT time between females and males ( = 0.156). The intervention induced improvements in left ventricular (LV) diastolic function (+13% for myocardial ') along with increased LV mass (+13%) in females ( ≤ 0.039) but not in males ( ≥ 0.257). During the initial LBNP stages (0 to -20 mmHg), LV stroke volume and cardiac output were exclusively increased in females after the intervention ( ≤ 0.034). In conclusion, the cardiac phenotype of females with advanced age can be structurally and functionally modified in parallel to improved OT via short-term hematological and central hemodynamic stimuli. Based on previous studies, main features of the cardiac phenotype in females with advanced age are generally unresponsive to lifestyle interventions. The present findings reveals that the cardiac phenotype of middle-age and older females is amenable to large modification in a short-term period when hematological stimuli are combined with those induced by exercise training. The same intervention only induced minor adaptations in males matched by age and potential confounding factors.