Sex-Specific Physiology and Cardiovascular Disease

Abstract

Sex differences in cardiovascular diseases can be classified as those which are specific to one sex and those that differ in incidence, prevalence, etiology, symptomatology, response to treatment, morbidity, and mortality in one sex compared to the other. All sex differences in cardiovascular conditions have their basis in the combined expression of genetic and hormonal differences between women and men. This chapter addresses how understanding basic mechanisms of hormone responses, imaging diagnostics, and integration of genomics and proteomics has advanced diagnosis and improved outcomes for cardiovascular conditions, apart from those related to pregnancy that are more prevalent in women. These conditions include obstructive coronary artery disease, coronary microvascular dysfunction, spontaneous coronary artery dissection, diseases of the cardiac muscle including heart failure and takotsubo cardiomyopathy, and conditions related to neurovascular dysregulation including hot flashes and night sweats associated with menopause and effects of exogenous hormones on vascular function. Improvement in technologies allowing for noninvasive assessment of neuronally mediated vascular reactivity will further improve our understanding of the basic etiology of the neurovascular disorders. Consideration of sex, hormonal status, and pregnancy history in diagnosis and treatment protocols will improve prevention and outcomes of cardiovascular disease in women as they age.

Keywords: 17β-Estradiol; Atrial fibrillation; Cardiomyopathy; Coronary microvascular dysfunction; Endothelial dysfunction; Heart failure; Hot flashes; INOCA; Ischemic nonobstructive coronary artery disease; Menopause; Migraine; SCAD; Spontaneous coronary artery dissection; Takotsubo; Vasomotor symptoms.

Figure 27.1.

Composite representation of four patterns of vasomotor instability relative to their onset prior to menopause, the intensity of events and their duration relative to menopause reported in three contemporary studies. [–77]

Figure 27.2.

Impact of hormonal contraception on mechanisms of cardiovascular disease. *Dependent on delivery route of estrogen; **dependent on type of progestin; ***dependent on the dose of estrogen. Cox-2 = cyclooxygenase-2; HDL = high-density lipoprotein; LDL= low density lipoprotein; VSMC = vascular smooth muscle cell. Reproduced with permission from reference [117].

Figure 27.3.

A population study of ccardiovascular mortality in women who underwent bilateral oophorectomy before age 45 years and were or were not treated with estrogen through age 45 years or longer. Reproduced with permission from reference [124].