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.

Keywords: arterial stiffness; estrogen; hypertension; pulse wave velocity; sex.

Fig. 1.

A: healthy artery. Energy generated by distension of the arterial wall during systole is used during diastole to maintain blood flow and decrease pulse pressure downstream. B: stiffened artery. Poor energy absorption results in higher pulse pressure, reduced flow during diastole, increased cardiac afterload, and end organ damage.

Fig. 2.

Graphical representation of the number of peer-reviewed articles containing the search term “arterial stiffness” alone or with the additional search term “sex” through 2017.

Fig. 3.

Graphical abstract denoting interactions of sex, disease, and mechanisms in arterial stiffness. ER, estrogen receptor; GPER, G protein-coupled ER; AR, androgen receptor.