Cardiovascular Diseases Commons^™

Infective Endocarditis Hospitalizations In Kentucky, 2008-2018: Spatial And Temporal Trends, Meera Marji, Steve Browning, W. Jay Christian, Richard Charnigo, Steve W. Leung, Anna Kucharska-Newton

Journal of Appalachian Health

Introduction: Infective endocarditis (IE) hospitalization rates have increased significantly in the last decade, primarily due to the opioid epidemic. In 2016, Kentucky (KY) ranked among the top ten states for opioid-related overdose deaths, but limited data exist on IE trends in KY.

Purpose: This study seeks to examine county-level spatial and temporal trends in IE hospitalization rates in KY.

Methods: Hospital inpatient discharge data from 2008–2018 for KY residents aged 18 and older were analyzed. IE admissions and drug use status were identified using ICD-9 & 10 diagnosis codes. U.S. Census data calculated yearly IE hospitalization rates per 100,000 residents. …

Renin-Angiotensin-Aldosterone System In Preeclampsia: Pathophysiological Insights And Links To Vascular Dementia, Robin C. Finch, Jenny Lutshumba, Elizabeth Mirsky, Esther Ndashaala, Kelsey Bullens, Emma Smith

Pediatrics Faculty Publications

Pre-eclampsia, a condition characterized by new-onset hypertension during pregnancy and one or more indices of organ damage, is a major driver of both short and long-term maternal health outcomes. Individuals with a history of pre-eclampsia are at increased risk for cardiovascular, renal, and other chronic diseases. Recent studies have linked pre-eclampsia history with increased risk of dementia later in life, underscoring the importance of new guidelines emphasizing blood pressure control to reduce the risk of cognitive decline. Unfortunately, neither mechanisms underlying causes of pre-eclampsia nor their links with cognitive function are well understood. Vascular contributions to cognitive impairment and dementia …

A Tale Of Two Serpins: Pathologic And Protective Roles Of Agt And Pai-1 In Metabolic And Cardiovascular Disease, Alex C. Pettey

Theses and Dissertations--Physiology

Metabolic and cardiovascular diseases are leading causes of morbidity and mortality worldwide. Conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD), aortic aneurysm, and cardiac fibrosis have limited pharmacological therapies, underscoring the need for deeper mechanistic investigations. Serine protease inhibitors (serpins) have been implicated in these pathologies and represent potential therapeutic targets. Despite structural homology, serpins regulate diverse physiological processes through both protease inhibition and non-inhibitory mechanisms. This dissertation examines the roles of two serpins, angiotensinogen (AGT) and plasminogen activator inhibitor-1 (PAI-1), in preclinical models of metabolic and cardiovascular disease to identify novel mechanisms that may inform future therapeutic strategies. …

Biochemical And Biophysical Properties Of Failing Myocardium In Rare Patient Populations, Gregory Nathaniel Milburn

Theses and Dissertations--Physiology

Heart failure has diverse underlying etiologies, complicating research. While some types, like ischemic disease or inherited mutations, are well-studied, research on rarer forms has lagged. Understanding the molecular drivers in these populations may enhance diagnostics and therapies. This work examines two rare groups: patients with ATTR cardiac amyloidosis and those receiving mechanical assist device support. We show that myocardium from patients with amyloidosis has increased fibrosis and reduced force production without changes in cross-bridge kinetics. Additionally, we show that the passive stiffness of amyloidosis myocardium is not different from non-failing myocardium, indicating increased ventricular wall thickness may cause restrictive filling. …

Biochemical Properties Of Cardiac Sarcomeres In Human Heart Failure, Austin Grey Wellette-Hunsucker

Theses and Dissertations--Physiology

Heart failure (HF) exhibits considerable heterogeneity, posing significant challenges for research involving human cohorts. Diastolic dysfunction is a common pathophysiological feature; however, its molecular mechanisms remain incompletely elucidated. Sarcomeric proteins are integral to cardiac contraction and relaxation. Nonetheless, the phosphoproteome and the structural remodeling effects of these proteins on diastolic function within the context of HF have not been comprehensively characterized. This study examined sarcomeric modifications in diastolic dysfunction in human HF, focusing on Dilated and Ischemic HF, with non-failing donor hearts as controls. Analyzing myocardial samples from ~150 patients using electrophoretic and biochemical techniques, it found significant titin remodeling …

Rad Reduction Reveals Therapeutic Potential Of Targeting Cardiomyocyte L-Type Calcium Channel Regulation For Heart Failure, Garrett Elmore

Theses and Dissertations--Physiology

Heart failure (HF) is prevalent and is predicted to increase with the aging population. Dilated cardiomyopathy (DCM) is a common cause of systolic HF. Current therapies fail to address principal issues: compromised systolic function and dysfunctional Ca²⁺ handling. No therapeutic approach exists for direct, positive modulation of cardiomyocyte L-type calcium channels (LTCC). RAD (Ras associated with diabetes) is a key regulator of the cardiac LTCC. RAD is a downstream phosphorylated target of the ß-adrenergic receptor (ß-AR)/cAMP/protein kinase A pathway; phosphorylation augments LTCC activity, contributing to chronotropy, inotropy, and lusitropy. RAD overexpression results in LTCC inhibition, whereas knockout positively modulates …

The Potential Beneficial Role Of Anti-Platelet/Anti-Coagulant Medications On Diabetic Retinopathy: A Scoping Review Protocol, Sarah Draud, Qingjun Wang, Lauren E. Robinson

Markey Cancer Center Faculty Publications

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes mellitus (DM, both types 1 and 2), affecting millions of individuals worldwide. DM is known to induce changes in platelet function and hemostasis, thereby elevating the risk of thrombotic incidents. The hyperglycemic environment in DM can trigger platelet hyperactivity, potentially exacerbating the onset and progression of DR. Despite the intricate pathophysiology of DR, which involves oxidative stress, inflammation, retinal neovascularization, and the disruption of the blood-retina barrier, the specific mechanisms underlying platelet hyperactivity in the microvasculature of DM patients remain inadequately explored. Antiplatelet and anticoagulation medications have proven beneficial in …

Long-Term Cardiometabolic Effects Of Preconceptional And Prenatal Opioid Exposure In The Adult Offspring, Nermin Hassan Mohamed Selim Ahmed

Theses and Dissertations--Pharmacology and Nutritional Sciences

Opioid use disorder (OUD), one of the greatest public health threats in the US, requires urgent attention. In 2022, the CDC reported 107,941 overdose deaths, over 70% attributed to synthetic opioids such as fentanyl (FEN). An alarming increase in opioid use disorder (OUD) diagnoses in pregnant people resulted in a 5-fold rise in cases of neonatal opioid withdrawal syndrome (NOWS). This condition elicits sympathetic overactivity, neural hyperexcitability, and a stress reaction characterized by tachycardia and hypertension. Whether prenatal exposure to fentanyl induces cardiovascular dysfunction in the offspring remains undetermined, impeding the timely development of strategies to mitigate OUD-related health risks …

Cardiovascular Disease Among Commercially Insured Adults With Type 1 Diabetes In The Us , 2016-2019, Orighomisan F. Agboghoroma

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Objectives: The objective of this study is to examine the overall as well as age- and sex-specific burden of cardiovascular disease (CVD) among adults with type 1 diabetes (T1D) in the US using nationwide commercial claims data from 2016-2019.

Research Design and Methods We used nationwide commercial claims data (1/1/2016-12/31/2019) from Merative™MarketScan to identify adults ≥20 years with T1D (ascertained using ICD-10 codes). CVD was ascertained using ICD-10 diagnostic codes for myocardial infarction, atrial fibrillation, ischemic heart disease, heart failure, peripheral arterial disease, and stroke. The annual prevalence and age-specific prevalence of CVD were calculated. Age-adjusted prevalence of CVD …

Exenatide As Chronopharmacotherapy For T2dm Associated Complications: Targeting Nondipping Blood Pressure And Sleep Insufficiency, Aaron Chacon

Theses and Dissertations--Pharmacology and Nutritional Sciences

Although largely impacted by age, race and ethnicity, and socioeconomic factors, Type 2 Diabetes Mellitus (T2DM) is primarily driven by obesity, currently affecting ~30 million in the U.S and ~463 million globally. T2DM carries numerous complications, including high prevalence of hypertension and nondipping blood pressure (BP), sleep insufficiency and fragmentation. Nondipping BP is an inadequate drop in BP (≤ 10%) during sleeping hours compared with waking hours. Lending to this, sleep disturbance acts as both precursor and consequence of metabolic dysregulation, greatly impacting circadian rhythmicity. To model these conditions, we utilized diabetic (db/db) mice. These mice carry a point mutation …

Cell-Based Cardiac Repair And The Natural Cardiac Healing In Regenerative Adult Mammal, Hsuan Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Heart failure (HF) following myocardial infarction (MI) remains a significant global health concern, with the initial ischemic injury often leading to microvascular damage and infarct expansion, exacerbating the overall cardiac impairment. Despite extensive research, there are currently no effective therapies to limit myocardial damage post-MI, resulting in a substantial number of patients progressing to HF. Stem cell therapy has emerged as a promising approach to modulate cardiac injury and promote healing. However, clinical trials have shown only modest success, underscoring the need for improved strategies to enhance efficacy. Additionally, the lack of significant ventricular regeneration highlights the necessity of targeting …

Improving Nutrition Screening Practice In The Hospitalized Heart Failure Patient Population, Amanda J. Bourgeois

DNP Projects

Background: Heart Failure is a disease known to affect nearly 6.5 million adults in the United States. Characterized by recurrent hospitalizations, heart failure significantly contributes to morbidity, mortality, and healthcare costs in the United States and worldwide. Because malnutrition is prevalent in the heart failure population, healthcare providers must perform nutritional assessments on admission to intervene in the case of malnutrition, prevent deterioration, and improve patient prognosis. Without intervention and early identification of malnutrition, heart failure hospitalizations will remain a significant problem.

Purpose: The purpose of this study is to evaluate the effect of an evidence-based educational program for cardiac …

Sex Differences In Cardiometabolic Risk Factors In Youth With Obesity, Lucrecia Valdez

Theses and Dissertations--Nutrition and Food Systems

Background: The prevalence of hypertension in children and adolescents is rising, with 13% having elevated blood pressure and 5% having hypertension. Sex differences play a role in cardiovascular diseases in adults but are not well defined in youth. The objective of this study is to identify sex differences in obesity-mediated cardiometabolic risk factors in adolescents. Methods: This is a pilot study of n=82 youth with obesity recruited from a High BMI Clinic. Clinical data and blood samples were collected at a single time point. Serum sterols were quantified via LC-MS/MS. Number of cardiometabolic risk factors were evaluated. Data are mean …

The Role Of High Mobility Group Box-1 Pathobiology In Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Shayan Mohammadmoradi

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs) are permanent luminal dilations of the vessel wall that can result in rupture and death. There is currently no evidence-based treatment to prevent or attenuate the development of this devastating condition. Although vascular inflammation is known to be one of the hallmarks of AAA, underlying mechanisms that initiate inflammatory pathways in the aorta are not clearly known. High-mobility group box 1 (HMGB1), a highly conserved nonhistone DNA-binding nuclear protein, may contribute to vascular diseases. Since whole-body genetic deletion of HMGB1 is embryonic lethal, pharmacological approaches have been used to manipulate HMGB1 in mice. However, it remains …

Exploring The Efficacy Of Mir-33 Antagonism In Promoting Regression Of Intracranial Atherosclerosis In A Nonhuman Primate Model, Peter Hecker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we …

Sex Dimorphisms Of Aldosterone And High Salt Induced Aortic Aneurysms In Mice, Xufang Mu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aortic aneurysms, a permanent enlargement in the aorta, is a devastating disease with a high mortality rate after rupture. Aortic aneurysms exhibit strong sex dimorphisms: men are at higher risk than women while women experience worse outcomes if diagnosed. Currently, the only intervention is by open surgery or endovascular repair, and no drugs are approved for blunting the disease progression. This highlights the needs for mechanistic studies for sex-specific therapeutic targets.

Our lab established the mouse model in which mineralocorticoid receptor (MR) agonist aldosterone induces aortic aneurysms in the presence of high salt in male mice age-dependently, mimicking the aging …

The Relative Contribution Of Liver And Intestine In Reverse Cholesterol Transport, Rupinder Kaur

Theses and Dissertations--Pharmacy

Despite decades of advances in research, death due to cardiometabolic disease remains the largest contributor to mortality in the US. While present therapies oppose “forward cholesterol transport,” and atherosclerotic plaque progression, they do not remove cholesterol from established atherosclerotic plaques. Reverse cholesterol transport (RCT) is the active process of mobilizing peripheral cholesterol for excretion through the hepatobiliary (transhepatic cholesterol elimination, THCE) or intestinal (transintestinal cholesterol elimination, TICE) pathways. Currently, there are no clinically approved therapeutics that target RCT. Elucidation of the mechanisms that govern RCT and TICE, and the subsequent identification of novel targets is of importance. The present work …

Dietary Assessments And Their Association With Psychological Factors, Inflammation, And Cardiovascular Health Outcomes, Junghee Kang

Theses and Dissertations--Nursing

Cardiovascular diseases (CVDs), a group of disorders of the heart and blood vessels, are the leading cause of death worldwide, causing one-third of deaths each year. Diet is one of the most important behavioral risk factors for CVD. The effects of behavioral risk factors, such as diet, may lead to increased blood pressure, increased blood glucose, raised blood lipids, and overweight and obesity. Inflammation contributes to the development of CVD and can be influenced by diet. Dietary assessment indices can measure diet quality from an individual's dietary intake by scoring food and nutrient intakes. However, the mediation effects of diet …

Identification And Characterization Of Epitope Specific Immune Responses In Humans And Mice, David Henson

Theses and Dissertations--Pharmacy

Cardiovascular disease (CVD) is a major cause of morbidity and mortality around the world causing approximately 14% of total disease burden. A major factor in the progression to major CVD within patients is immune activation, which led to the study of various immune products as potential biomarkers for the prediction of cardiovascular events, including antigen-specific antibodies and immune complexes. One focus of this biomarker research is IgG autoantibodies targeting apolipoprotein A-I (ApoA-I), and several studies of these antibodies have found an association with increased CVD events. Based on the encouraging results from these studies and previous research which has identified …

Rad Modulation Of The L-Type Calcium Channel Confers Systolic Advantage In The Heart, Brooke Mildred Ahern

Theses and Dissertations--Physiology

Heart failure is a major public health problem and a leading cause of mortality. This clinical condition affects populations of all ages, and is the result of various cardiomyopathies. Almost half of these patients suffer specifically from heart failure with reduced ejection fraction; these hearts have decreased performance due to a failure of the heart to contract with sufficient force to meet demand. While there are therapies available to increase contractility, none of these enhance contraction without also further promoting pathological signaling and remodeling.

Under normal physiological conditions, the body elevates cardiac output through the fight-or-flight response. This response activates …

Characterization Of Spontaneous Preeclampsia In The African Green Monkey (Chlorocebus Aethiops Sabaeus), Chelsea Christina Weaver

Theses and Dissertations--Biology

Hypertensive pregnancy disorders are a major contribution to maternal and neonatal mortality worldwide. Two of these disorders, preeclampsia and chronic hypertension in pregnancy, affect up to 10% of all pregnancies. These hypertensive disorders of pregnancy are associated with long-term, postnatal risk factors for both mother and offspring. Despite numerous recent advances in preeclampsia research, the underlying mechanisms are still not understood. This could be due to lack of a spontaneous animal model. This dissertation presents the African Green Monkey (AGM; Chlorocebus aethiops sabaeus) as the first known spontaneous animal model of preeclampsia and a highly translational model of chronic …

Evaluating The Effect Of An Electronic Health Record Patient Portal On The Management Of Hypertension, Ashley Hall

DNP Projects

Background: Hypertension is the leading cause of cardiovascular disease and affects individuals globally, nationally, and locally. Consequences of uncontrolled hypertension include atherosclerosis, heart failure, stroke, and renal disease. The electronic health portal is a patient-specific, interactive tool that has been shown to promote adherence to provider recommendations and improve chronic disease management.

Purpose: The purpose of this project was to determine the effects of education via an electronic healthcare portal on the blood pressure management of adults at a primary care clinic in a small town in Kentucky.

Methods: This study was a one-group pre/post intervention designed to evaluate provider …

Associations Between Psychosocial Stressors, Genes, And Cardiovascular Disease In At-Risk Adults, Kaitlin Voigts Key

Theses and Dissertations--Nursing

Psychosocial stressors have a significant adverse impact on cardiovascular health. While better medical treatments and increased emphasis on healthy lifestyle have improved cardiovascular health for many in the United States over the past 50 years, there are persistent inequities in cardiovascular disease (CVD) rates, with the highest rates among populations burdened by chronic exposure to psychosocial stressors such as discrimination and anxiety, among others. Genetic factors may interact with these stressors further influencing the rates of CVD in these populations. The purpose of this dissertation is to examine associations among psychosocial stressors and other CVD risk factors, and the influence …

Responses To Symptoms Among Patients With Heart Failure, Chin-Yen Lin

Theses and Dissertations--Nursing

Patients with heart failure (HF) suffer from chronic and progressive symptoms. Failure to respond appropriately to escalating symptoms of HF causes a delay in seeking care, which results in worse symptom status, frequent rehospitalizations, and contributes to higher mortality. In order to enhance HF self-care, promote timely care-seeking, and improve outcomes, identification of factors that affect patients’ responses to symptoms and their decisions to seek care is essential. Thus, the purposes of this dissertation were to (1) identify factors associated with patients’ responses to worsening HF symptoms, and (2) determine the impact of responses to symptoms on outcomes in patients …

Involvement Of The Renin Angiotensin System In Marfan Syndrome Associated Thoracic Aortic Aneurysms, Jeff Zheying Chen

Theses and Dissertations--Physiology

Thoracic aortic aneurysms (TAAs) are clinically-silent dilations of the aorta which greatly increase the risk of aortic rupture, a condition with 50-90% mortality. Marfan syndrome (MFS) is caused by mutations in fibrillin-1 (FBN1) and is associated with TAAs. Due to an absence of validated and effective pharmacologic therapies to prevent or reverse TAA, most MFS patients require surgical aortic repair. Understanding MFS associated TAA pathogenesis would direct development of new pharmacologic therapies. Previous research has implicated the renin angiotensin system in TAA. In both males and females, angiotensinogen (AGT) is cleaved serially to generate the main effector peptide angiotensin II …

Cardiac Effects Of Obesity During Pregnancy In C57bl/6j Mice, Kayla Lynn Dudick

Theses and Dissertations--Nutrition and Food Systems

Objective: Pregnancy requires profound cardiac and metabolic adaptation. Left ventricular (LV) mass is increased in response to pregnancy, but is not associated with cardiac damage. In contrast, obesity-mediated cardiac hypertrophy is pathological. Data from animal studies indicate dietary fatty acid composition may have a protective effect during states of extreme cardiac physiological adaptation. In contrast, aberrant cardiac metabolism is a hallmark of disease. Over a third of reproductive-age women in the United States are obese, but there is a paucity of data describing the effect of obesity on maternal cardiac adaptation to pregnancy. The objective of this study was to …

Don't Just Check The Box: Check Your Athlete's Heart: Adding A 12-Lead Ecg To Pre-Participation Screening To Identify High Risk Of Sudden Cardiac Arrest In Male High School Athletes, Shannon King

DNP Projects

PURPOSE: Sudden cardiac arrest (SCA) continues to be the leading cause of death in male high school athletes participating in competitive sports. There is gap in the current preventative screening practice of history and physical alone. The purpose of this project is to evaluate adding a 12-lead electrocardiogram (ECG) to pre-participation screening captures cardiac abnormalities that identify male athletes at a higher risk for developing SCA. METHODS: A descriptive secondary analysis design to determine the incidence of cardiac abnormalities detected with the addition of a 12-lead ECG during pre-participation screenings (annual sports physical) of high school-aged male athletes. The study …

Managing Intracranial Hemorrhage In Patients With A Durable Continuous Flow Left Ventricular Assist Device, Godly Jack, Phil Barker, Ryan Searcy, Jason N. Katz

The VAD Journal

Background: While intracranial hemorrhage (ICH) is a known complication of left ventricular assist device (LVAD) support, and is associated with high morbidity and mortality, optimal care pathways have neither been elucidated nor reported. We describe management of LVAD patients following ICH, with a focus on anticoagulation, operative interventions, care team designation, complications, and outcomes.

Methods: We retrospectively reviewed all durable continuous-flow LVAD implantations at our academic medical center from January 2007 to July 2018. Patients who experienced ICH after LVAD were identified. We defined baseline and ICH characteristics, medical and surgical interventions, care teams, and outcomes including death, device thrombosis, …

Xx Sex Chromosome Complement Promotes Atherosclerosis In Mice, Yasir Alsiraj, Xuqi Chen, Sean E. Thatcher, Ryan E. Temel, Lei Cai, Eric M. Blalock, Wendy Katz, Heba M. Ali, Michael C. Petriello, Pan Deng, Andrew J. Morris, Xuping Wang, Aldons J. Lusis, Arthur P. Arnold, Karen Reue, Katherine L. Thompson, Patrick Tso, Lisa A. Cassis

Pharmacology and Nutritional Sciences Faculty Publications

Men and women differ in circulating lipids and coronary artery disease (CAD). While sex hormones such as estrogens decrease CAD risk, hormone replacement therapy increases risk. Biological sex is determined by sex hormones and chromosomes, but effects of sex chromosomes on circulating lipids and atherosclerosis are unknown. Here, we use mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We assess atherosclerosis in multiple models and experimental paradigms that distinguish effects of sex chromosomes, and male or female gonads. Pro-atherogenic lipids and atherosclerosis are greater in XX than XY mice, indicating …

Successful Extracorporeal Membrane Oxygenation In The Management Of Acute Respiratory Distress Syndrome And Cardiopulmonary Collapse Secondary To Amniotic Fluid Embolism, Sumon Roy, Nishit A. Biniwale, Venkata S. Pendela, Patricia Oates, Katrina Wojciechowski, Scott C. Feitell

The VAD Journal

Amniotic fluid embolism (AFE) is one of the most devastating complications of pregnancy that typically manifests as acute cardiopulmonary collapse during delivery or in the postpartum period. The potential role of extracorporeal membrane oxygenation (ECMO) as a management technique in severe cases of AFE remains largely unknown given the limited literature available. In this report, we present the first case, to our knowledge, of successful implementation of ECMO as a life-saving measure in a case of hemorrhagic shock due to postpartum bleeding complicated by severe AFE leading to acute respiratory distress syndrome (ARDS) ultimately requiring tracheostomy. Hemodynamic decompensation is often …