Abstract Body: Background: Lean body mass (LBM) is strongly associated with the capacity to deliver and consume O2 in women, according to pilot studies in women and men with low LBM. A yet unknown principle of cardiovascular physiology might underlie previous preliminary findings.

Research question: Is LBM a major determinant of the circulatory dimorphism in humans?

Aims: To assess the relationship of LBM with a comprehensive set of hematological, hemodynamic, cardiac and aerobic exercise capacity variables, collectively portraying the structure and function of the circulatory system in women and men.

Methods: Healthy women and men (n=294) matched by age and physical activity throughout the adult lifespan (18-78 yr) were included. Body composition (DXA), hemoglobin mass and intravascular volumes, cardiac structure, function and hemodynamics and aerobic exercise capacity were assessed in standardized conditions. Main variables included LBM, circulating hemoglobin mass, blood volume, arterial blood pressure, systemic vascular resistance, left ventricular (LV) mass/volumes/remodeling/elastance, peak cardiac output/O2 consumption/power output. Linear regression assessed the relationship of LBM with study variables in each sex. Sex comparisons were performed in non-LBM-matched (n=294) and LBM-matched (n=70) cohorts.

Results: LBM linearly associated with the majority of hematological, hemodynamic, cardiac and exercise capacity variables in women (P ≤ 0.018) and men (P ≤ 0.010). The slopes of the regression lines did not differ between sexes (P ≥ 0.082); women falling in the lower and men in the upper range of the overall relationship of LBM with these variables. Accordingly, in non-LBM-matched individuals, marked sex differences were observed in most variables (P < 0.001). In LBM-matched individuals, no cardiac-related variable (structure, function, blood pressure, systemic vascular resistance, aerobic capacity) differed between women and men.

Conclusions: In humans, irrespective of sex, cardiac structure, function, blood pressure, vascular resistance and aerobic exercise capacity are determined by LBM. Therefore, sex dimorphisms in the circulatory system are a function of the metabolically active mass, rather than sex.