Emory University School of Medicine
Emory University School of Medicine
Department of Medicine

Specialized Center of Research Excellence on Sex Differences (SCORE) section navigation

Department of Medicine

Past Years

2021 - 2022

Matthew Parsons, PhD

Assistant Professor

Yerkes National Primate Research Center
ASSESSMENT OF BIOLOGICAL SEX-BASED DIFFERENCES IN NATURAL KILLER CELL FC RECEPTOR EXPRESSION AND FUNCTION IN THE RECTAL MUCOSA
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WHY SEX MATTERS IN SCIENCE:

...Because we do not yet know whether there are sex-based differences in the way that the immune system responds to the detected presence of HIV in rectal tissue.

ABSTRACT

A preventative vaccine is urgently needed to reduce the global burden of new HIV infections. A leading strategy for preventing HIV infection is the induction of antibodies directed to the viral envelope glycoproteins. The protective efficacy of anti-HIV antibodies has been demonstrated in a clinical trial of a human HIV vaccine candidate and in the non-human primate (NHP) model of HIV exposure. Antibody-conferred protection from HIV is mediated through viral neutralization and the elimination of antibody-opsonized viral particles and infected cells through antibody Fc-dependent functions, such as antibody-dependent cellular cytotoxicity (ADCC).

ADCC is mediated by effector cells following the ligation of cell surface Fc receptors (FcR) by antibody bound to the surface of infected cells. Our current understanding of anti-HIV ADCC has primarily been established through in vitro assays using effector cells derived from peripheral blood. Natural killer (NK) cells are major and well characterized mediators of ADCC within peripheral blood. As HIV exposures primarily occur at anogenital mucosae, it is important to determine the frequency and Fc-dependent functional potential of mucosal NK cells. In recent experiments, we observed FcR-expressing NK cells within rectal biopsies collected from macaques, an NHP commonly used in models of HIV exposure. The capacity of rectal FcR-expressing NK cells to mediate anti-HIV antibody Fc-dependent functions has not yet been assessed.

An important variable to consider for assessments of NK cell frequency and function is biological sex. The frequency and cytotoxic potential of peripheral blood and lymphoid tissue NK cells has been shown to be higher in biological males. In the current proposal, we will conduct the initial assessment of the impact of biological sex on the frequency and function of FcR-expressing NK cells within the macaque rectal mucosa. We hypothesize: (1) the frequency of FcR-expressing NK cells will be higher in the rectal mucosa of male macaques compared to females; and (2) the Fc-dependent functions of FcR-expressing NK cells will be higher in the rectal mucosa of male macaques compared to females.

In Aim 1, we will assess the impact of biological sex on the frequency of FcR-expressing NK cells within the rectal mucosa. The proposed experiments will confirm the presence of FcR-expressing NK cells in the rectum and determine if biological sex influences their frequency.

In Aim 2, we will assess the impact of biological sex on the anti-HIV Fc-dependent functions of rectal FcRexpressing NK cells. These experiments will determine the capacity of rectal FcR-expressing NK cells to mediate Fc-dependent functions and the impact of biological sex on this capability.

The proposed research is an important step towards designing HIV vaccine strategies that specifically engage immune cells present within anogenital mucosae and confer protection from HIV across biological sexes.

Cesar Romero, MD, PhD

Instructor of Medicine

Renal Division
Department of Medicine
Emory School of Medicine
SEX DIFFERENCES AND HYPERTENSION: EFFECTS ON NMDA RECEPTORS
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WHY SEX MATTERS IN SCIENCE:

...Because even though women experience a protective effect from high blood pressure (hypertension) -- which, if untreated, is the main cause of heart attack, stroke, and the need for dialysis -- during their fertile age, their risk for hypertension increases dramatically, even more so than in men, in their postmenopausal period and we don't know why.

ABSTRACT

Hypertension is the leading single risk factor for mortality worldwide. However, in more than 90% of hypertensive patients, the cause is unknown. There is sex differences in hypertension prevalence. Thus, women has a relative protection for hypertension in the fertile age. However, this difference disappears in the post menopause period and after 70 years old, women have a higher hypertension prevalence. The sex difference in hypertension is not very well understood and estrogen has been found to play a role on the pathogenesis of hypertension. Thus, there is a need to understand the complex mechanisms associated with postmenopause hypertension and the role of estrogens, in order to develop more personalized treatment for women.

Connecting tubule-glomerular feedback (CNTGF) is kidney feedback mechanism that facilitates sodium excretion under certain physiological situations by inducing vasodilation. It has been previously demonstrated that e N-methyl-D-aspartate receptors (NMDAr) can induce renal vasodilation by sensitizing the CNTGF. Dr. Romero's long-term objectives are to explore the consequences of impaired vasodilation in the kidney as a cause of hypertension and develop a program to thoroughly understand some of the causes of human hypertension.

The main hypothesis of the current proposal is that estrogen increase the function of NMDAr favoring sodium and water excretion and that the lack of estrogen down regulates NMDAr inducing hypertension, explaining part of the sex differences observed in hypertension, specially in postmenopause period. The hypothesis will be addressed through the following specific aims: AIM 1: To determine the effects of estradiol on BP and NMDA receptor expression in the kidney. We hypothesized that estradiol will increase NMDA receptor expression in the kidney and decrease blood pressure. We will use neutered male mice infused with estradiol or vehicle and compare NMDAr expression, function, and signalin. Blood pressure and renal hemodynamic will also be compared between the groups. AIM 2: To evaluate the protective effect of NMDA receptors in hypertension in post-menopause mice. We hypothesize that an NMDA agonist will prevent hypertension development in post-menopause females. We will use the accelerated ovarian failure (AOF) mice model induced by 4-vinylcyclohexane diepoxide injection in a model of angiotensin II-induced hypertension. We will treat the AOF hypertensive females with NMDA potentiator or vehicle. Four groups will be compared. The primary outcome will be blood pressure level. Secondary outcomes will be RFR and NMDA expression. Dr. Romero will be guided by Dr. Eaton as a principal mentor as well as Dr. Reckelhoff as co-mentor. Overall, this proposal will allow us to explore deep causes of post-menopause hypertension and contribute to the scientific advances on woman's health. In addition, this pilot funding will allow us to open a new line of research in sex differences in hypertension, for future grant submission.

Jill Ward, PhD

Assistant Profesor

Department of Cell Biology
Emory School of Medicine
ENHANCING AXON REGENERATION WITH SEX-DEPENDENT EXERCISE THERAPIES
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WHY SEX MATTERS IN SCIENCE:

... Because males and females experience enough differences in the way their bodies work to repair nerve damage following injury that there may be benefits to designing sex-differentiated exercise protocols that promote nerve regeneration. 

ABSTRACT

Peripheral nerve injuries are common with more than 200,000 new cases reported each year in the United States alone. Only about 10% of these individuals regain much function. Nerve injuries significantly impact the long-term quality of life, and many injured individuals seek continued life-long treatments for associated disabilities and pain. The common reason given for the poor functional outcomes is the process of axon regeneration. Over the past decade, our laboratory has shown that exercise strikingly enhances peripheral axon regeneration and significantly improves functional recovery following complete nerve. However, the translational potential of exercise has limitations. Many patients are not candidates for exercise due to issues, such as co-morbidities that preclude rehabilitation, necessary immobilization of a limb following surgical nerve repair, unknown dose requirement of exercise and patient compliance. We propose here to investigate a novel signaling mechanism (hypoxia inducible factor 1, HIF1) to promote sensory, motor, and sympathetic axon regeneration.

Based on the literature, we suggest that HIF1α may be the key mediator of how exercise robustly promotes axon regeneration after nerve injury. The HIF complex controls the transcription of numerous genes associated with neurogenesis, neuronal survival, neuronal metabolism, and angiogenesis. De-regulation of HIF1α has been identified in several neurodegenerative diseases (e.g., amyotrophic lateral sclerosis) and neural injuries (e.g., spinal cord injury and stroke). Notably, neuronal HIF1α was shown to be required for axon regeneration after peripheral nerve injury.

With pilot data, we show that the exercise protocol we have shown to enhance axon regeneration after sciatic nerve injury upregulates HIF1α in axotomized motoneurons. We also show that by pharmacologically stabilizing HIF1α, axons also elongate even farther than after treatment with exercise. This suggests that optimizing HIF1α signaling may lead to better regeneration and functional recovery. The goal of this study will be to investigate the fundamentals of stabilizing HIF1α by sex-dependent exercise protocols in axotomized neurons to treat peripheral nerve injuries in males and females.

2020 - 2021

Brittany Butts, PhD

Assistant Professor

Nell Hodgson Woodruff School of Nursing
SEX DIFFERENCES IN INFLAMMATORY CORRELATES OF HEART FAILURE SYMPTOMS
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WHY SEX MATTERS IN SCIENCE:

...Because we do not yet understand the inflammation-related physiological underpinnings anchoring the clinical reality that men and women experience heart failure differently, with women suffering significantly higher symptom burden, morbidity, and mortality.

ABSTRACT

Heart failure (HF) is a progressive, terminal illness with frequent decompensation related to ventricular remodeling. Because HF remains a leading cause of morbidity and mortality in the United States, identification of novel therapeutic targets that may slow disease progression are urgently needed. There are significant sex differences in HF clinical course and outcomes, with morbidity and mortality significantly higher in women than in men. These differences have been linked to differences in inflammation. Women develop HF later in life than men, and thus have a difference clinical course them men. Inflammatory burden increases with age and promotes the development of cardiovascular disease. Previous studies suggest that sex may moderate the relationship between inflammation and depressive symptoms in cardiometabolic disease, but the relationship in HF is unknown. Adequate symptom management in HF requires both comprehensive symptom assessment and sufficient knowledge of available approaches to alleviate symptoms related to both HF and common comorbidities. Thus, understanding the physiological underpinnings of physical symptoms (i.e. fatigue) and emotional symptoms (i.e. depression) can direct treatment strategies. However, few studies have found significant associations between symptoms and objective physical or psychological measures in HF. Further understanding of the underlying mechanisms of each symptom in persons with HF and the role of comorbidities is needed. This proposal adds an exploratory sub-study to an ongoing pilot study, currently in progress, that examines symptoms and metabolomic pathways in Black adults with HF. Thus, this study addresses the disparities in morbidity and mortality experienced by two at-risk populations by examining sex differences in inflammation and the symptoms of depression and fatigue in Black adults living with HF. By examining sex as a biological variable in the relationship between inflammation and symptoms in HF, this study will advance our understanding of symptoms and address the gaps in knowledge that will lead to more precise symptom-reducing interventions in HF.

Matthew Gribble, PhD

Assistant Professor

Department of Environmental Health
Rollins School of Public Health
SEX-SPECIFIC GENETICS OF SALT SENSITIVITY IN FAMILIES FROM SOUTHWEST COASTAL BANGLADESH
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WHY SEX MATTERS IN SCIENCE:

...Because even though rising sea levels are changing the salinity of ground water in coastal communities, potentially leading to increases in hypertension among salt-sensitive people, very little is known about the extent that genetic influences by sex play in the biological response to salts that can affect blood pressure.

ABSTRACT

Salt sensitivity is thought to play an important role in blood pressure, and there are likely biological sex differences in salt sensitivity. Salt exposures in many coastal communities are changing as a consequence of sea-level rise and adaptation attempts to blunt the harms of that climate change impact. The purpose of this SCORE pilot is to leverage data from a climate change adaptation trial in southwest coastal Bangladesh, which diluted groundwater and reduced exposure to a number of salts including magnesium, calcium, sodium, and potassium, to better understand biological sex differences in response to salts for blood pressure, in particular genetic influences by sex. This work involves application of novel approaches to gene-environment interactions, which could be more broadly useful across scientific applications.

Monika Stojek, PhD

Assistant Profesor

Department of Psychiatry and Behavioral Sciences
Emory School of Medicine
DYSREGULATED EATING AND INFLAMMATION IN WOMEN AND MEN WITH AND WITHOUT PTSD
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WHY SEX MATTERS IN SCIENCE:

... Because despite the fact that dysregulated eating is more prevalent in women, and women are more likely to develop PTSD following trauma exposure, sex differences in dysregulated eating or inflammation have not been examined in those with vs. without PTSD diagnosis. 

ABSTRACT

Increased systemic inflammation is characteristic of obesity and cardiometabolic dysfunction, and has been linked to posttraumatic stress disorder (PTSD) diagnosis presence and severity. Although rates of cardiometabolic dysfunction are similar in women and men, women have higher mortality rates from these conditions. Women also have higher rates of PTSD diagnosis. Dysregulated eating behaviors include binge eating and behaviors traditionally associated with substance misuse (i.e., food addiction), and are more prevalent in the general population than threshold eating disorders. They also have been shown to be more prevalent among those with trauma histories compared to those without. Dysregulated eating behaviors, even when not meeting full threshold for eating disorders diagnosis, contribute to obesity and metabolic dysfunction. Compared to men, women have higher prevalence of dysregulated eating, including food addiction (FA). However, we do not know to what extent FA is associated with PTSD diagnosis or inflammation severity, and whether there are sex differences in these relationships. Therefore, the aims of this study include examining the combined effect of sex and PTSD diagnosis on FA severity (Aim 1) and inflammation severity (Aim 3), and examining the combined effect of sex and FA diagnosis on inflammation severity (Aim 2) in post-9/11 women and men veterans seeking treatment for PTSD, anxiety, or depression. We hypothesize that women with PTSD will report significantly higher FA severity compared to the other groups (i.e., women without PTSD, men with PTSD, men without PTSD) and that women with FA will report the highest inflammation severity compared to other groups (i.e., women without FA, men with FA, men without FA). We will also explore the inflammatory profiles of women and men with and without PTSD. The proposed study is innovative because the relationships between FA and PTSD diagnosis or FA and inflammation have not been examined. It is also innovative in the recruitment of a veteran sample, a population in which eating behaviors have been understudied, despite rates of obesity and metabolic dysfunction similar to the general population. The results from this study will provide empirical basis for examining the efficacy of a combined/concurrent PTSD and eating dysregulation intervention on PTSD symptoms, eating dysregulation behaviors, and metabolic syndrome components. By understanding the biological and psychological correlates of dysregulated eating, we have the potential to develop effective and efficient behavioral interventions that concurrently target emotional and dysregulated eating symptoms, and putatively, the neuroendocrine and immune systems.

Samaah Sullivan, PhD

Assistant Profesor

Department of Epidemiology
Rollins School of Public Health
STRESS AND OVARIAN AGING ON CARDIOVASCULAR RISK
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WHY SEX MATTERS IN SCIENCE:

... Because coronary heart disease (CHD) is the number one cause of death among women. Women with CHD have less obstructive coronary artery disease yet greater risk of myocardial ischemia compared with similarly aged men and there is growing recognition that emotional stress and physiological sex differences in response to stress are important in women's cardiovascular vulnerability. There is a higher burden of psychosocial factors including depression, early life adversity, posttraumatic stress disorder (PTSD), poverty and neighborhood disadvantage among women than men with CHD. In addition to having a greater prevalence of psychosocial stressors, women may be more vulnerable to the adverse effects on stress/mental health on CHD, risk as shown in prior research. Several studies have suggested that women with CHD are at higher risk of adverse cardiovascular outcomes than men in the presence of psychosocial exposure. 

ABSTRACT

The purpose of this SCORE pilot proposal is to provide preliminary data and new training on stress and sex hormone biology to understand mechanisms of sex differences in cardiovascular disease and potential disparities among women. The premise of this research project is based on the applicant's own research which suggest that compared to men of similar age, women (and particularly, younger women) with coronary heart disease have distinct vascular mechanisms in relation to stress and myocardial ischemia, and have higher basal and stress-related inflammation, and are more likely to develop myocardial ischemia during mental stress. The underlying explanation for these sex differences is unknown; however, one potential mechanism involves sex hormone biology among premenopausal women and across the menopausal transition. Stress may impair female reproduction through diminished ovarian reserve and induce earlier age at menopause, which have been associated with cardiovascular risk, possibly through sex hormone-related pathways influencing immune response, vascular, and cardiac function. The overall goal of this project is to understand mechanisms for sex differences in inflammatory and vascular responses to mental stress, and the role of ovarian function and menopausal status among women. The applicant will leverage the infrastructure of the Myocardial Infarction and Mental Stress Study 2 (MIMS2: R01HL109413), which was recently renewed for a new enrollment wave with the same methods (MIMS3: 2R01HL109413). The two waves will eventually total 300 women with a recent MI, ≤ 60 years of age (mean and median age 50 yr). All data for MIMS2 is currently completed including data on anti-Müllerian Hormone (AMH), a biomarker of ovarian reserve and menopausal status in women on 150 MI women and 58 age-matched community controls. During the first year of recruitment for MIMS3 (expected start date of Jan. 2020), an additional 30 MI women and 30 controls will be enrolled, allowing the applicant to collect additional AMH assays on these participants and obtain a larger sample size, achieving a combined total of 180 MI women and 88 controls from MIMS2 and MIMS3 for this pilot project. The scientific aims of this project are to: 1) Examine differences in gonadal aging and age at menopause between women with MI and age-matched control women; 2) Examine whether gonadal aging (lower AMH levels) is associated with greater inflammation and vascular response to mental stress among women with MI compared to age-matched control women; and 3) Examine whether psychosocial stressors (e.g., depression, early life adversity, discrimination, and socioeconomic disadvantage) are associated with gonadal aging (lower AMH levels) among women with a recent MI and age matched controls. The new enrollment of patients and controls will provide key opportunities for training and data collection on gonadal aging and vascular function to inform the development of future NIH-R01 proposals.

Kathryn Wood, PhD

Profesor

Nell Hodgson Woodruff School of Nursing
DO MECHANISMS OF FATIGUE AFTER ATRIAL FIBRILLATION ABLATION DIFFER BY SEX?
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WHY SEX MATTERS IN SCIENCE:

... Because Over 6 million patients in the U.S. have atrial fibrillation (AF), the most common irregular heart rhythm, effectively treated by AF ablation but sex-linked differences that would enable physicians to potentially predict which AF patients are at highest risk of fatigue and/or negative ablation outcomes have not yet been studied. 

ABSTRACT

The goal of the proposed research is to determine whether increased fatigue following cardiac ablation therapy for atrial fibrillation (AF) is associated with increased inflammation and to test whether differences exist by sex. AF is the most common, costly cardiac arrhythmia affecting over 6 million people in the U.S. and a major public health problem with a 2-fold increase in mortality. No cure exists for AF, but our best treatment to improve quality of life is AF ablation (AFA). From our prior pilot study, patients reported severe fatigue that can last up to three months after AFA treatment, negatively affecting quality of life. In order to prevent this trajectory, it is critical to identify those patients at highest risk so that evidence based interventions can be developed and tested. Understanding the characteristics and mechanisms of fatigue is critical to its successful management and the development of targeted therapies. In cancer and HIV, fatigue has been documented to occur as a response to inflammation associated with elevated inflammatory (cytokines, high sensitivity C-reactive protein) and oxidative stress markers. These biomarkers have not been studied in relation to AF symptoms such as fatigue. The long-term goal of this research is to identify mechanisms of AF-related fatigue using inflammatory and oxidative stress markers and to investigate whether there is an interactive effect of inflammatory factors by sex on fatigue. Thus, this study will compare levels of AF-related fatigue, and inflammatory and oxidative stress markers, in 20 AFA subjects (10 men, 10 women) pre- and post-AFA (at time points of baseline [pre-AFA], and at 1 and 3 months post-AFA). Patients will have biomarkers drawn and complete symptom questionnaires at each measurement point. Patients will also wear a cardiac patch monitor for two weeks at each time point to measure sleep, fatigue, and amount of AF versus normal rhythm. Understanding characteristics and mechanisms of AF fatigue and identification of potential outcome endpoints are critical to successful identification of those at highest risk of negative outcomes. Addressing these aims will identify fatigue patterns and biomarkers to be used in a subsequent R01 proposal to develop and test targeted interventions to improve outcomes in high-risk adults with AF.

2019 - 2020

Jessica Alvarez, PhD

Assistant Professor

Division of Endocrinology, Metabolism, and Lipids
Department of Medicine
Emory School of Medicine
USE OF HIGH-RESOLUTION PLASMA METABOLOMICS TO DETERMINE LINKAGES BETWEEN ESTROGEN INDUCED BONE LOSS AND INTESTINAL BARRIER IN HIV
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WHY SEX MATTERS IN SCIENCE:

... Because HIV-induced bone loss may be particularly significant in older women due to exacerbated fracture risk from loss of estrogen.

ABSTRACT

With improved medical care, including the introduction of successful antiretroviral therapies (ART), the age demography of HIV/AIDS has shifted so that it is projected that over half of all individuals living with HIV are now over 50 years old. A new landscape of HIV is now apparent, with a high rate of age-related comorbidities that are exacerbated by HIV infection and side effects of ART. Bone loss and resulting osteopenia/osteoporosis and bone fracture risk are alarmingly high in individuals with HIV, especially postmenopausal women where both estrogen deficiency and HIV infection/ART contribute to inflammation induced bone loss. Recent research implicates dysregulation of the gut microbiome and increase in gut mucosal permeability (“leaky gut”) causing influx of inflammatory mediators, such as lipopolysaccharide (LPS), as contributors to bone loss. By contrast, a healthy microbiome can protect against bone loss via production of bacterial-derived short chain fatty acids (SCFA) that stimulate bone formation (bone anabolic). Furthermore, studies suggest that estrogen deficiency and HIV infection both independently contribute to loss of gut barrier integrity. The specific interactions between gut permeability, estrogen deficiency, and HIV-infection are, however, not known. We hypothesize that bone loss in women with HIV infection is due, in part, to gut dysbiosis driving imbalance between bone catabolic and bone anabolic bacterial metabolites, and exacerbated by estrogen insufficiency/deficiency. Recent advances in high-resolution metabolomics (HRM) provide a unique opportunity to broadly explore metabolism and underlying pathways relevant to HIV and women’s health. The purpose of this SCORE pilot study is to use plasma HRM with advanced bioinformatics to interrogate the interrelationships between circulating gut-bacterial derived metabolites, bone mineral density (BMD) and biomarkers of bone formation and loss, and estrogen deficiency in women living with HIV. Aim 1 will assess the association of circulating bacterial-derived metabolites and HIV status with bone turnover and BMD, while Aim 2 will assess the interactions of estrogen on these relationships. The overall goal of this project is to obtain new insight into HIV- and estrogen deficiency-induced bone loss that will inform the design of future interventions to reduce the risk for osteoporosis and fracture among women living with HIV. This SCORE grant will provide outstanding preliminary data for subsequent NIH R-level studies focusing on the pathophysiology of bone disease among women living with HIV and the development of new strategies to improve health and quality of life in this aging population.

Allison LoPilato, PhD

Assistant Profesor

Department of Psychiatry and Behavioral Sciences
Rollins School of Public Health
SEX DIFFERENCES IN THE RISK PREDICTION OF SERIOUS MENTAL ILLNESS
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WHY SEX MATTERS IN SCIENCE:

... Because clinical risk prediction models for serious mental illness (e.g., schizophrenia, bipolar disorder) have not yet included sex as a variable of interest. This is a surprising and critical omission, given that sex differences are widely observed in the clinical presentation, functional outcome, and neuroanatomy of individuals with serious mental illness. Additionally, most SMI samples have a larger proportion of males, which may obscure risk markers of greater relevance to females when sex is not taken into consideration. Although this compromises risk prediction for both sexes, females are disproportionally affected. A better understanding of sex differences in clinical risk profiles, and the integration of sex into prediction model development, will improve the effectiveness of our risk prediction tools and early interventions for both men and women.

ABSTRACT

Early identification and preventative interventions are the key to ameliorating the personal, social, and economic burden associated with serious mental illness (SMI). Accurate risk prediction models that can identify individuals prior to illness onset are critical to these early intervention efforts. Over the past two decades, clinical high risk (CHR) research designs have identified risk markers that predict conversion to SMI. These risk markers have been used to develop prediction models that estimate an individual’s likelihood of developing SMI based on their risk profile. However, research on these approaches has only recently been conducted, and has not yet included sex as a variable of interest. This is a critical omission, given that sex differences are widely observed in the clinical presentation, functional outcome, and neuroanatomy of individuals with SMI. The current project will systematically evaluate and incorporate sex differences into clinical risk prediction models for serious mental illness (SMI). The limited investigation of sex differences in CHR research is a serious problem for the power and utility of current risk prediction tools. To address these concerns, we will utilize data from the North American Longitudinal Prodromal Study (NAPLS), the largest CHR study to date (n=764) to: 1) identify sex differences in risk predictors, 2) examine sex differences in the performance of the current NAPLS risk calculator, and 3) test whether prediction can be improved by developing sex specific models. A better understanding of sex differences in CHR risk profiles, and the integration of sex into prediction model development will improve the effectiveness of our risk prediction tools and early interventions.

Puja Mehta, MD

Assistant Profesor

Division of Cardiology
Department of Medicine
Emory School of Medicine
SEX DIFFERENCES IN CORONARY MICROVASCULAR DYSFUNCTION
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WHY SEX MATTERS IN SCIENCE:

... Because although Coronary Microvascular Disease is a clinical problem that disproportionately affects women, previous research on high-risk plaque features that would indicate vulnerability to CMD has not taken sex as a biological variable into account. 

ABSTRACT

Approximately two-thirds of women with chest pain who are suspected of having myocardial ischemia and undergo coronary angiography are actually found to have no obstructive coronary artery disease (CAD) (<50% luminal stenosis). Evidence over the past two decades indicates that coronary microvascular dysfunction (CMD) may be an explanation in such cases. CMD is associated with an adverse cardiovascular prognosis and an estimated 3 million women are impacted by CMD. Ischemic heart disease risk factors (such as hypertension, dyslipidemia, insulin resistance, and estrogen loss) promote a pro-inflammatory, pro-oxidative state which is associated with CMD. Our preliminary data show an increase in inflammation/oxidative stress in CMD. It is unclear whether abnormal microvascular function in these patients is independent of epicardial plaque burden, albeit it is non-obstructive CAD. Furthermore, sex-differences in high risk plaque features (HRP) that would indicate vulnerability have not been investigated in CMD. HRPs can be detected reliably and efficiently by coronary computed tomography angiography (CCTA) using a low radiation exposure protocol. We hypothesize is that compared to men, women with CMD have more HRP features. We further hypothesize that this difference will be reflected in increased systemic inflammation/oxidative stress in women. To support this hypothesis, the PI proposes to collect pilot data in 28 subjects (ages ≥ 50 years) to study HRP features by CCTA in those diagnosed with CMD compared to non-CMD controls. CMD is diagnosed by a low coronary flow reserve of <2.0 (n=14). Controls will include subjects with a normal coronary flow reserve ≥ 2.0 (n=14). Each group will have an equal number of men and women. We will only include post-menopausal women in this pilot proposal. The findings from this proposal will support an R01 application submission next year to study sex-differences in CMD.