Abstract
Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality. Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men. The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age. Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely.
Highlights
Sex differences from a medical perspective may include: 1) diseases/conditions specific to one sex, 2) diseases/conditions that disproportionately affect one sex, and 3) diseases/ conditions having distinctly different causes, manifestations, outcomes, or treatments depending on sex
Sex differences in autonomic function related to sympathetic control of the vascular resistance, and to the synthesis, uptake, and disposition of adrenergic neurotransmitters may explain the greater incidence of hypertension in men and the greater incidence of vasospastic diseases, such as migraine, Raynaud’s disease, and postural orthostatic tachycardia syndrome (POTS) in women [7]
Sex differences in the composition of the vascular and cardiac extracellular matrix contribute to the greater incidence of diastolic heart failure and transient apical ballooning syndrome (Takotsubo cardiomyopathy) in women compared to men [8,9,10]
Summary
Sex differences from a medical perspective may include: 1) diseases/conditions specific to one sex, 2) diseases/conditions that disproportionately affect one sex, and 3) diseases/ conditions having distinctly different causes, manifestations, outcomes (morbidity or mortality), or treatments depending on sex. It is possible to evaluate populations of circulating microvesicles, in early as well as late disease processes (e.g., development of white matter hyperintensities, β-amyloid pathology of Alzheimer’s disease, structural MRI changes associated with neuronal degeneration), and to study their associations with the cognitive health of women who have experienced preeclampsia, menopause, or who have used MHT. The effects of MHT on 1) the number and cellular origins of microvesicles, 2) the development of white matter hyperintensities, and 3) on direct measures of cerebral vasodilatory capacity remain to be determined These studies can be extended to men in order to evaluate the association of testosterone deficiency with overall cardiovascular risk and cognitive decline
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