Elucidating the Relationship Between Insomnia, Sex, and Cardiovascular Disease

Sex differences in cardiovascular disease (CVD) mortality have been attributed to differences in pathophysiology between men and women and to disparities in CVD management that disproportionately affect women compared to men. Similarly, there has been investigation of differences in the prevalence and presentation of insomnia attributable to sex. Few studies have examined how sex and insomnia interact to influence CVD outcomes, however. In this review, we summarize the literature on sex-specific differences in the prevalence and presentation of insomnia as well as existing research regarding the relationship between insomnia and CVD outcomes as it pertains to sex. Research to date indicate that women are more likely to have insomnia than men, and there appear to be differential associations in the relation between insomnia and CVD by sex. We posit potential mechanisms of the relationship between sex, insomnia and CVD, discuss gaps in the existing literature, and provide commentary on future research needed in this area. Unraveling the complex relations between sex, insomnia, and CVD may help to explain sex-specific differences in CVD, and identify sex-specific strategies for promotion of cardiovascular health. Throughout this review, terms “men” and “women” are used as they are in the source literature, which does not differentiate between sex and gender. The implications of this are also discussed.

Exploring Fetal Sex as a Risk Factor for Sleep Disordered Breathing and Its Complications in Pregnancy

Sleep disordered breathing (SDB) is a common, yet under-recognized and undertreated condition in pregnancy. Sleep disordered breathing is associated with pregnancy complications including preeclampsia, gestational diabetes, preterm birth, as well as severe maternal morbidity and mortality. The identification of risk factors for SDB in pregnancy may improve screening, diagnosis, and treatment of SDB prior to the onset of pregnancy complications. The goal of this study was to determine whether fetal sex increases risk of SDB in pregnancy. A cohort of singleton (N = 991) pregnant women were recruited within 24 to 48 hours of delivery and answered questions regarding SDB symptoms by questionnaire. Women who reported frequent loud snoring at least 3 times a week were considered to have SDB. Hospital records were reviewed to extract information on fetal sex and pregnancy complications including preeclampsia, pregnancy-induced hypertension, gestational diabetes, preterm delivery, and low birth weight. Women carrying male fetuses were significantly more likely to have SDB (β = .37, P = .01, OR: 1.45 [95% CI: 1.09-1.94]). Fetal sex was associated with increased risk of hypertensive disorders of pregnancy (defined as preeclampsia and/or pregnancy-induced hypertension) among women with SDB in pregnancy (β = .41, P = .02, OR: 1.51 [95% CI: 1.08-2.11]). Fetal sex did not increase risk of preterm birth, low birth weight, or gestational diabetes among women with SDB in pregnancy. Women carrying male fetuses were approximately 1.5 times more likely to report SDB in pregnancy compared to women carrying female fetuses, and women with pregnancy-onset SDB carrying male fetuses were 1.5 times more likely to have hypertensive disorders of pregnancy compared to women with SDB carrying female fetuses. Confirmation of fetal sex as a risk factor may, with other risk factors, play a role in identifying women at highest risk of SDB complications in pregnancy.

Roundtable Discussion III: The Development and Uses of Artificial Intelligence in Medicine: A Work in Progress

Humans have devised machines to replace computation by individuals since ancient times: The abacus predated the written Hindu–Arabic numeral system by centuries. We owe a quantum leap in the development of machines to help problem solve to the British mathematician Charles Babbage who built what he called the Difference Engine in the mid-19th century. But the Turing formula created in 1936 is the foundation for the modern computer; it produced printed symbols on paper tape that listed a series of logical instructions. Three decades later, Olivetti manufactured the first mass-marketed desktop computer (1964), and by 1981, IBM had developed the first personal computer. Computing machines have become more and more powerful, culminating recently in Google’s claim that it had achieved quantum supremacy in developing a system that can complete a task in 200 seconds that it would take the most powerful type of classical computer available 10 000 years to achieve. In short, we are in a period of human history in which we are creating more and more powerful and complex machines potentially capable of duplicating human intelligence and indeed surpassing/expanding its power. We are solidly in the age of artificial intelligence (AI). Increasing interest in the development of AI and its application to human health at all levels makes a roundtable discussion by experts a valuable project for publication in our journal, Gender and the Genome, the official journal of the Foundation for Gender-Specific Medicine and the International Society of Gender Medicine.

Three Decades of Progress in Sleep Disorders and Sleep Health for Women

Over the past 3 decades, significant strides have been made in the field of sleep medicine for women. The impact of sex and gender on sleep health and sleep disorders received little attention in the early 1990s, but driven by policies ensuring inclusion of women in medical research, more recent studies have identified sex differences in sleep and investigated gender differences in sleep disorders. Nevertheless, disparities remain: diagnosis of sleep disorders, such as obstructive sleep apnea, narcolepsy, and rapid eye movement (REM) sleep behavior disorder are often delayed and underdiagnosed in women. Future research should continue to examine how biological sex and identity across the gender spectrum influence sleep health and sleep disorders, allowing for more personalized health care for all patients.

Sex- and Gender-Related Factors in Blood Product Transfusions

Blood products are indicated for a plethora of conditions in several settings, with a variety of products available for transfusion, from highly processed specific components to whole blood. Matching the donor product to the recipient is crucial in avoiding serious transfusion reactions, with the extent of matching depending on the physiological need, setting, and product. There are important factors related to sex and gender differences in donated blood products, adverse reactions to those products, interplay with underlying pathology, as well as sociocultural differences in the collection. This article will review key sex- and gender-specific research related to the use of blood products with an emphasis on the acute care setting.

Gender Differences in Endothelial Function and Coronary Vasomotion Abnormalities

Introduction: Structural and functional abnormalities of coronary microvasculature, referred to as coronary microvascular dysfunction (CMD), have been implicated in a wide range of cardiovascular diseases and have gained growing attention in patients with chest pain with no obstructive coronary artery disease, especially in females. The central mechanisms of coronary vasomotion abnormalities encompass enhanced coronary vasoconstrictive reactivity (ie, coronary spasm), reduced endothelium-dependent and -independent coronary vasodilator capacities, and increased coronary microvascular resistance. The 2 major endothelium-derived relaxing factors, nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) factors, modulate vascular tone in a distinct vessel size–dependent manner; NO mainly mediates vasodilatation of relatively large, conduit vessels, while EDH factors in small resistance vessels. Endothelium-dependent hyperpolarization–mediated vasodilatation is more prominent in female resistance arteries, where estrogens exert beneficial effects on endothelium-dependent vasodilatation via multiple mechanisms. In the clinical settings, therapeutic approaches targeting NO are disappointing for the treatment of various cardiovascular diseases, where endothelial dysfunction and CMD are substantially involved. Significance: In this review, we will discuss the current knowledge on the pathophysiology and molecular mechanisms of endothelial function and coronary vasomotion abnormalities from bench to bedside, with a special reference to gender differences. Results: Recent experimental and clinical studies have demonstrated distinct gender differences in endothelial function and coronary vasomotion abnormalities with major clinical implications. Moreover, recent landmark clinical trials regarding the management of stable coronary artery disease have questioned the benefit of percutaneous coronary intervention, supporting the importance of the coronary microvascular physiology. Conclusion: Further characterization and a better understanding of the gender differences in basic vascular biology as well as those in cardiovascular diseases are indispensable to improve health care and patient outcomes in cardiovascular medicine.

Cystic Fibrosis and Genotype-Dependent Therapy: Is There a Need for a Sex-Specific Therapy?

Cystic fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulation (CFTR) anion channel. Loss of CFTR protein and/or function disrupts chloride, bicarbonate, and fluid transport and also impacts epithelial sodium transport. Such altered ion and fluid transport produces mucus obstruction, inflammation, pulmonary infection, and damage to multiple organs. Although an autosomal disease, it is apparent that gender differences in life expectancy and quality of life do exist. Conventionally established therapies have treated the downstream sequelae of CFTR dysfunction and have led to a steady increase in life expectancy. Physicians now have access to medications that treat the basic defect in CF, in the form of CFTR modulators. These drugs target the trafficking and/or function of CFTR to improve clinical outcomes for patients. This review summarizes the science behind CFTR modulators and shows how these drugs have dramatically changed how patients with CF are treated. Surprisingly, although the drug target(s) are identical in males and females, CF females seem to display a greater improvement than their male counterparts.

Eye Conditions in Women

Changes in vision can have significant impact on health and quality of life. Differences between women and men have been identified in the incidence of several eye conditions. Some of these differences are a result of the greater longevity of women. However, the eye, like other organs, is susceptible to the impacts of inflammation and sex steroids. Conditions, such as thyroid eye disease, optic neuritis, and dry eye disease are related to autoimmune or inflammatory conditions and are, thus, more common among women. Idiopathic intracranial hypertension occurs disproportionately in women of childbearing age; the etiology of this condition appears to be related to both inflammatory and sex hormone fluctuations.

Contemplating on the Etiology of COVID-19 Severity and Mortality Sex Differences

COVID-19 displays a sex-biased behavior with a higher rate of intensity and mortality in men. In that sense, COVID-19 deflects-off the typical trend of many viral infections which are characterized by a higher rate of intensity and prevalence in males, yet a higher female mortality rate. Severity and mortality rates of COVID-19 are associated with several underlying diseases, which exhibit significant self-sufficient male-biased dimorphism, thus are at times hypothesized to be the ones responsible to tilt mortality balance toward higher men death in COVID-19. Yet, similar comorbidities prevail in other viral infections, raising curiosity to what makes COVID-19 unique? The answer may lay in the involvement of renin-angiotensin system and ACE2 receptor in COVID-19 progression, 2 players which are significant contributors to the fatality of COVID-19. A structured difference is evident in the expression and function of RAS and ACE2 between the sexes, presumably tipping over mortality rate tendency toward male-risk factor.