Beyond sex differences: equivalent adaptations across the O2 transport chain after exercise-based cardiac rehabilitation in women and men with coronary heart disease

Background: Exercise-based cardiac rehabilitation (CR) improves peak oxygen uptake ([V]O2peak) in patients with coronary heart disease (CHD); however, whether women and men exhibit similar adaptations across the steps of O2 transport remains unknown. We aimed to compare the ventilatory and circulatory determinants of [V]O2peak changes between women and men with CHD following a structured exercise training program. Methods: A total of 28 women (27%) and 75 men (73%) with CHD, matched for age, body mass index, and [V]O2peak (% predicted), underwent maximal cardiopulmonary exercise testing (CPET) before and after 12 weeks of CR. [V]O2peak and minute ventilation ([V]E) were measured breath by breath. Heart rate and cardiac output ([Q]c)were assessed non-invasively using impedance cardiography. Exercise efficiency ({Delta}[V]O2/{Delta}W), alveolar ventilation ([V]A), ventilatory efficiency (OUES), O2 pulse, arteriovenous oxygen content difference (C(a-[v])O2) and gross muscular efficiency (W) were calculated using standard equations. Mixed model analyses (sex x time) were used to compare training-induced changes between sexes. Results: At baseline, values of [V]O2peak (absolute and normalized by fat free mass), [V]E, [V]A, O2 pulse, C(a-[v])O2, {Delta}[V]O2/{Delta}W, W were significantly lower in women than in men with CHD (group effect, p<0.01). [V]O2peak normalized by fat-free mass improved similarly in both sexes after CR (p<0.0001, no significant sex x time interaction). Pulmonary convection ([V]E, [V]A), ventilatory efficiency (OUES), circulatory convection ([Q]c, cardiac index, O2 pulse), and peripheral gross muscular efficiency (W) all improved similarly after CR in women and men (effect sizeXtime effect, p<0.05, no significant group x time interaction). The prevalence of responder categories did not differ between sexes (p=0.826). Conclusion: Women and men with CHD demonstrated equivalent O2 transport phenotype adaptations after CR, with comparable improvements across the O2 transport chain (pulmonary, circulatory, and peripheral determinants of [V]O2peak).