Abstract Body: Background: The reason why women present with markedly augmented (up to +50 %) cardiac and large arterial elastances relative to men, remains unknown. Such a sex dimorphism may explain the increased prevalance of left ventricular hypertrophy and heart failure with preserved ejection fraction in women.

Research Question: Does lean body mass (LBM) explain the the sex dimorphism in cardiac and large arterial elastances?

Objectives: To test the hypothesis that LBM and its physiological correlate, systemic vascular resistance (SVR), explain the sex dimorphism in cardiac and large arterial elastances.

Methods: A total of 303 women (n=149) and men (n=154) throughout the adult lifespan (18-78 yr) matched by age and physical activity were included. LBM, fat and bone mass were determined by dual-energy X-ray absorptiometry. Left ventricular mass, structure and hemodynamics were assessed by echocardiography and continuous blood pressure measurements. Body composition variables were included as potential mediators in the association of sex with cardiac (end-systolic (Ees), diastolic (Ed)) and large arterial (Ea) elastances.

Results: Ees, Ed and Ea were augmented (≥24 %) in women relative to men (P<0.001). Sex (men:1, women:2) was positively associated with Ees (β=0.52, P<0.001), Ed (β=0.84, P<0.001) and Ea (β=0.78, P<0.001). Body weight did not substantially mediate the relationship of sex with Ees, Ed and Ea. Body fat only had a very minor partial mediation effect in the relationship of sex with Ees and Ea. LBM partially mediated the relationship of sex with Ees (β=0.29) and Ed (β=0.49) and completely mediated the relationship of sex with Ea (β=0.74). SVR predominantly mediated the mediation effect of total and leg LBM in the relationship of sex with Ea (β≥0.46).

Conclusion: Markedly elevated large arterial elastance in women is fully mediated by reduced LBM and increased SVR relative to men.