An In-Silico Study of Sex Differences in Carotid Hemodynamic Waveforms

Arterial stiffening, a natural process occurring with age, is a recognized risk factor for cardiovascular disease. Sex differences in vascular aging have been observed, with females experiencing increased aortic stiffness after menopause. Carotid hemodynamic waveforms-derived pressure and flow augmentation indices (pAIx and fAIx) are considered a potential tool for the non-invasive assessment of arterial stiffness. These tend to be higher in females, with a larger age-related increase. Alongside differences in arterial stiffness, other factors such as smaller height have been suggested as contributing factors. This in-silico study employs one-dimensional (1D) hemodynamic modeling to explore the determinants of sex-related differences in carotid augmentation indices. Male and female-representative in-silico carotid waveforms at the 3rd and 6th age decades were generated by parametrizing the models based on a literature survey of cardiovascular sex differences. Realistic sex differences in augmentation indices were reproduced by the models. Furthermore, a sensitivity analysis was performed to compare the effect of individual parameters on both pAIx and fAIx. Our findings reveal a variety of factors strongly influencing these indices, with a significant role played by the relative size of second-generation arteries with respect to the aorta.