New insights into arterial stiffening: does sex matter?

Abstract

This review discusses sexual dimorphism in arterial stiffening, disease pathology interactions, and the influence of sex on mechanisms and pathways. Arterial stiffness predicts cardiovascular mortality independent of blood pressure. Patients with increased arterial stiffness have a 48% higher risk for developing cardiovascular disease. Like other cardiovascular pathologies, arterial stiffness is sexually dimorphic. Young women have lower stiffness than aged-matched men, but this sex difference reverses during normal aging. Estrogen therapy does not attenuate progressive stiffening in postmenopausal women, indicating that currently prescribed drugs do not confer protection. Although remodeling of large arteries is a protective adaptation to higher wall stress, arterial stiffening increases afterload to the left ventricle and transmits higher pulsatile pressure to smaller arteries and target organs. Moreover, an increase in aortic stiffness may precede or exacerbate hypertension, particularly during aging. Additional studies are needed to elucidate the mechanisms by which females are protected from arterial stiffness to provide insight into its mechanisms and, ultimately, therapeutic targets for treating this pathology.

Neurovascular and Cognitive Dysfunction in Hypertension

“…Remodeling and stiffening result from interacting mechanical, humoral and cellular factors including hemodynamic stress, endothelial dysfunction, vascular inflammation, immune cell infiltration, and calcium deposition 69,70 . Both processes are driven by overlapping mediators including inflammatory cytokines, sex hormones, angiotensin-II (AngII), endothelin, aldosterone, and oxidative stress 71 . In addition, modifications of the extracellular matrix plays an essential role in stiffening.…”

“…A deficit in endothelial nitric oxide (NO) and free radicals may play an important role in remodeling. 56,71 In the aorta perivascular macrophages (PVM) expressing the lymphatic hyaluronan receptor LYVE1 safeguard the elasticity of the vascular wall by governing collagen content in smooth muscle cells through hyaluronan and pericellular matrix metalloprotease-9. 72 Although LYVE1+ PVM are present also in cerebral arteries, 72,73 it remains unclear if they serve a similar role in the homeostasis of the cerebrovascular wall.…”

The role of the gut microbiome in sex differences in arterial pressure

“…Studies directly linking the impact of the gut microbiome on sex differences in BP and hypertension are scarce. Arterial stiffness is closely related to hypertension; it is an independent predictor of cardiovascular risk and is particularly relevant to women, who see a marked rise in vascular stiffness after menopause, mirroring the rise in hypertension after menopause [66]. The decline in oestrogen clearly plays a central role in this relationship, but factors such as inflammation also contribute [67].…”

Sex moderates the relationship between aortic stiffness, cognition and cerebrovascular reactivity in healthy older adults

“…Overall, there is substantial evidence supporting an effect of sex hormone on vascular stiffness (Ogola et al 2018;DuPont et al 2019) . Over the lifespan, arterial stiffness increases linearly in both males and females however there is a more rapid increase in stiffness in females due to depletions in estrogen levels post menopause (Mitchell 2014;DuPont et al 2019) .…”