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Research

SCORE Pilot Projects

Brittany Butts

Brittany Butts, PhD Assistant Professor
Nell Hodgson Woodruff School of Nursing

Sex Differences in Inflammatory Correlates of Heart Failure Symptoms


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

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


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

Monika Stojek, PhD Assistant Professor
Department of Psychiatry and Behavioral Sciences
Emory School of Medicine

Dysregulated Eating and Inflammation in Women and Men with and without PTSD


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

Samaah Sullivan, PhD Assistant Professor
Department of Epidemiology
Rollins School of Public Health

Stress and Ovarian Aging on Cardiovascular Risk


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

Kathryn Wood, PhD Professor
Nell Hodgson Woodruff School of Nursing

Do Mechanisms of Fatigue after Atrial Fibrillation Ablation Differ by Sex?


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.

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