Cardiovascular Diseases Commons^™

Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background

Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.

Methods

CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and …

Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana

Annual Research Symposium

Natural phenolic compound Psoralidin limits cardiotoxicity associated with Doxorubicin

Lipoprotein(A) In Atherosclerotic Cardiovascular Disease And Aortic Stenosis: A European Atherosclerosis Society Consensus Statement, Florian Kronenberg, Samia Mora, Erik S G Stroes, Brian Ference Ference Ference, Benoit J. Arsenault, Lars Berglund, Marc R. Dweck, Marlys Koschinsky, Gilles Lambert, Salim S. Virani

Office of the Provost

This 2022 European Atherosclerosis Society lipoprotein(a) [Lp(a)] consensus statement updates evidence for the role of Lp(a) in atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis, provides clinical guidance for testing and treating elevated Lp(a) levels, and considers its inclusion in global risk estimation. Epidemiologic and genetic studies involving hundreds of thousands of individuals strongly support a causal and continuous association between Lp(a) concentration and cardiovascular outcomes in different ethnicities; elevated Lp(a) is a risk factor even at very low levels of low-density lipoprotein cholesterol. High Lp(a) is associated with both microcalcification and macrocalcification of the aortic valve. Current findings do …

H2s, Sg-1002, Protects Against Myocardial Oxidative Damage And Hypertrophy In Vitro Via Induction Of Cystathionine Β-Synthase And Antioxidant Proteins, Rahib K. Islam, Erinn Donnelly, Erminia Donnarumma, Fokhrul Hossain, Jason D. Gardner, Kazi N. Islam

School of Medicine Faculty Publications

Endogenously produced hydrogen sulfide (H2S) is critical for cardiovascular homeostasis. Therapeutic strategies aimed at increasing H2S levels have proven cardioprotective in models of acute myocardial infarction (MI) and heart failure (HF). The present study was undertaken to investigate the effects of a novel H2S prodrug, SG-1002, on stress induced hypertrophic signaling in murine HL-1 cardiac muscle cells. Treatment of HL-1 cells with SG-1002 under serum starvation without or with H2O2 increased the levels of H2S, H2S producing enzyme, and cystathionine β-synthase (CBS), as well as antioxidant protein levels, such as super oxide dismutase1 (SOD1) and catalase, and additionally decreased oxidative …

Lipoprotein(A), Oxidized Phospholipids, And Vascular Smooth Muscle Cell Phenotype And Viability, Michael Dunphy

Electronic Thesis and Dissertation Repository

Genetic studies have shown elevated plasma lipoprotein(a) (Lp(a)) levels to be an independent and causal risk factor for atherosclerotic cardiovascular disease and calcific aortic valve disease, however a definite mechanism for this pathogenicity has yet to be clearly identified. Oxidized phospholipids (oxPLs) have been implicated in facilitating atherogenic changes in the gene expression of vascular cells. As the primary carrier of oxPLs in the plasma, we hypothesize that Lp(a) contributes to vascular diseases by its enhanced ability to bind to and deliver oxPLs to tissue through a strong lysine binding site on its apolipoprotein(a) (apo(a)) component. Using a cultured primary …

Combination Sodium Nitrite And Hydralazine Therapy Attenuates Heart Failure With Preserved Ejection Fraction Severity In A “2-Hit” Murine Model, Kyle B. Lapenna, Zhen Li, Jake E. Doiron, Thomas E. Sharp, Huijing Xia, Karl Moles, Kashyap Koul, John S. Wang, David J. Polhemus, Traci T. Goodchild, Ravi B. Patel, Sanjiv J. Shah, David J. Lefer

School of Medicine Faculty Publications

BACKGROUND: Recent studies have suggested that cardiac nitrosative stress mediated by pathological overproduction of nitric oxide (NO) via inducible NO synthase (iNOS) contributes to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Other studies have suggested that endothelial NO synthase (eNOS) dysfunction and attenuated NO bioavailability contribute to HFpEF morbidity and mortality. We sought to further investigate dysregulated NO signaling and to examine the effects of a NO-based dual therapy (sodium nitrite+hydralazine) following the onset of HFpEF using a “2-hit” murine model. METHODS AND RESULTS: Nine-week-old male C57BL/6 N mice (n=15 per group) were treated concurrently with high-fat …

Reducing The Risk Of Mortality In Chronic Obstructive Pulmonary Disease With Pharmacotherapy: A Narrative Review, Matthew Mintz, Igor Barjaktarevic, Donald A. Mahler, Barry Make, Neil Skolnik, Barbara Yawn, Bree Zeyzus-Johns, Nicola A. Hanania

Abington Jefferson Health Papers

In 2020, chronic obstructive pulmonary disease (COPD) was the fifth leading cause of death in the United States excluding COVID-19, and its mortality burden has been rising since the 1980s. Smoking cessation, long-term oxygen therapy, noninvasive ventilation, and lung volume reduction surgery have had a beneficial effect on mortality; however, until recently, the effects of pharmacologic therapies on all-cause mortality have been unclear. Inhaled pharmacologic treatments for patients with COPD include combinations of long-acting muscarinic receptor antagonists (LAMAs), long-acting-β2-agonists (LABAs), and inhaled corticosteroids (ICS). The recent IMPACT and ETHOS clinical trials reported mortality benefits with ICS/LAMA/LABA triple therapy compared with …

Monoclonal Antibodies, Gene Silencing And Gene Editing (Crispr) Therapies For The Treatment Of Hyperlipidemia-The Future Is Here, Melody Hermel, Madison Lieberman, Leandro Slipczuk, Jamal S. Rana, Salim S. Virani

Office of the Provost

Hyperlipidemia is a significant risk factor for atherosclerotic cardiovascular disease. Undertreatment of elevated lipids persists despite existing therapies. Here, we provide an update on monoclonal antibodies, gene silencing therapies, and gene editing techniques for the management of hyperlipidemia. The current era of cutting-edge pharmaceuticals targeting low density lipoprotein cholesterol, PCSK9, lipoprotein (a), angiopoietin-like 3, and apolipoprotein C3 are reviewed. We outline what is known, studies in progress, and futuristic goals. This review of available and upcoming biotechnological lipid therapies is presented for clinicians managing patients with familial hyperlipidemia, statin intolerance, hypertriglyceridemia, or elevated lipoprotein (a) levels.

Recurrent Cyanotic Spells In An Octogenarian, Chin Tong Kwok, Chun Kit Wong

Journal of the Hong Kong College of Cardiology

We report rare case of an octogenarian who, after years of diagnostic delay, was found to have a patent foramen ovale, and due to an ascending aortic aneurysm that anatomically facilitated right-to-left shunt, presenting with life-threatening cyanotic attacks. The characteristic orthodeoxia-platypnea syndrome and high alveolar arterial gradient hint to the diagnosis. She was eventually treated successfully with urgent percutaneous PFO closure. Routine ordering of a transthoracic echocardiogram, without agitated saline injection under provocation maneuvers, may not be sufficient to rule out shunts.

Roles Of Exercise Treadmill Test In The Diagnosis & Risk Stratification Of Cardiac Channelopathies, Kit Chan

Journal of the Hong Kong College of Cardiology

Channelopathies are the leading causes of SCD in patients without structural heart disease. Missing the diagnosis of high-risk but concealed channelopathies could have lethal clinical consequences. However, the diagnosis of channelopathies is often challenging due to the dynamic clinical presentations and elusive ECG manifestations of these diseases. An integrated approach including clinical assessment, repeated electrocardiography, drug provocation tests, exercise stress test and genetic studies is often required for establishing the diagnosis. Pharmacological provocation tests may have limited sensitivity and may be associated with false positive results. Wide-spread use of genetic studies are limited by low yield, cost-effectiveness and availability issue. …

Retrospective Observational Study Comparing Two Reperfusion Strategies In Patients With Acute Stemi Presenting Outside Office Hours, Derek Pok-Him Lee, Kam-Tim Chan, Michael Kang-Yin Lee, Eric Chi-Yuen Wong

Journal of the Hong Kong College of Cardiology

Introduction : A pilot cluster-based 24-hour PPCI service in a phased expansion program was launched in October 2018. This study aimed to compare the 30-day mortality and major bleeding event in acute STEMI patients presenting outside office hours who received historical thrombolytic therapy and PPCI under the newly implemented 24-hour service model. Methods and results : A single center retrospective study was conducted on consecutive STEMI patients presenting outside office hours, who received urgent thrombolytic therapy or PPCI between 2016-2019. The primary endpoints were 30-day mortality and major bleeding event. The secondary endpoints were thrombolytic failure rate and hospital length …

The Impact Of Renal Insufficiency Upon Admission On The Clinical Outcome Of Patients With Acute St-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention, Wai Lun Kwong, Kwok Ho Yau, Eugene Sin, Kwok Keung Chan

Journal of the Hong Kong College of Cardiology

Background: Coronary artery disease is common in patients with renal insufficiency. In acute coronary syndrome, impaired renal function is present in approximately 30-40% of patients and is associated with worse prognosis. Local data regarding the risks and benefits for those patients suffering from acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) is scarce. We evaluated the clinical outcomes of patients suffering from STEMI with and without renal insufficiency upon admission who underwent PPCI.

Methods: From 1^st January 2009 to 30^th September 2017, all patients with STEMI treated with PPCI were identified. The primary …

Cardiometabolic Risk Factors Efficacy Of Semaglutide In The Step Program, Anastassia Amaro, Neil S. Skolnik, Danny Sugimoto

Abington Jefferson Health Papers

People with overweight or obesity often suffer from associated cardiometabolic diseases and comorbidities. Current therapies for obesity include lifestyle intervention, bariatric surgery, and pharmacotherapy. The magnitude of weight loss achieved with these therapies can determine the level of improvement in various comorbidities. Once-weekly subcutaneous semaglutide 2.4 mg is a glucagon-like peptide-1 receptor agonist recently approved by the US Food and Drug Administration for the treatment of obesity. This article reviews data from the global phase 3 Semaglutide Treatment Effect in People with obesity (STEP) program, comparing the efficacy of once-weekly subcutaneous semaglutide 2.4 mg versus placebo for weight loss and …

Determining The Proportionality Of Ischemic Stroke Risk Factors To Age, Elizabeth Hunter, John D. Kelleher

Articles

While age is an important risk factor, there are some disadvantages to including it in a stroke risk model: age can dominate the risk score and lead to over-or under-predictions in some age groups. There is evidence to suggest that some of these disadvantages are due to the non-proportionality of other risk factors with age, eg, risk factors contribute differently to stroke risk based on an individual’s age. In this paper, we present a framework to test if risk factors are proportional with age. We then apply the framework to a set of risk factors using Framingham heart study data …

Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling To Assess Peripheral Artery Disease, Olga A. Gimnich, Tatiana Belousova, Christina M. Short, Addison A. Taylor, Vijay Nambi, Joel D. Morrisett, Christie M. Ballantyne, Jean Bismuth, Dipan J. Shah, Gerd Brunner

School of Medicine Faculty Publications

BACKGROUND: Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). METHODS AND RESULTS: The computational microvascular model was used to study skeletal calf muscle perfusion in 56 in-dividuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast-enhanced magnetic resonance imaging and ankle-brachial index testing at rest and after 6-minute treadmill walking. We have determined associations of microvascular model parameters including the transfer …

Trend Of Left Ventricular Assist Device Related Complications: Insight From The National Inpatient Sample Database, Waqas Ullah, Muhammad Khawar Sana, Alexander G. Hajduczok, Yevgeniy Brailovsky, Donald C. Haas, Indranee N. Rajapreyar

Division of Cardiology Faculty Papers

No abstract provided.

A Qualitative Description Of Barriers To Visual Rehabilitation Experienced By Stroke Survivors With Visual Impairment In Alberta, Canada, Kiran Pohar Manhas, Katelyn Brehon, Jennis Jiang, Karim F. Damji, Fiona Costello

Department of Ophthalmology & Visual Sciences

Background: Post-stroke visual impairment (VI) is a common but under-recognized care challenge. Common manifestations of post-stroke VI include: diplopia, homonymous hemianopia, oscillopsia secondary to nystagmus, and visual inattention or neglect. In acute care settings, post-stroke VI recognition and treatment are often sub-optimal as emphasis is placed on survival. Stroke survivors with VI often face inconsistencies when accessing care out of hospital because variable availability and subsidization of visual rehabilitation. We sought to identify gaps in care experienced by stroke survivors with VI from stroke survivors' and care providers' perspectives.
Methods: We conducted a qualitative description study across 12 care sites …

Adolescent Psychological Assets And Cardiometabolic Health Maintenance In Adulthood: Implications For Health Equity, Farah Qureshi, Anne‐Josee Guimond, Elaine Tsao, Scott Delaney, Julia K. Boehm, Laura D. Kubzansky

Psychology Faculty Articles and Research

Background

Positive cardiometabolic health (CMH) is defined as meeting recommended levels of multiple cardiometabolic risk factors in the absence of manifest disease. Prior work finds that few individuals—particularly members of minoritized racial and ethnic groups—meet these criteria. This study investigated whether psychological assets help adolescents sustain CMH in adulthood and explored interactions by race and ethnicity.

Methods and Results

Participants were 3478 individuals in the National Longitudinal Study of Adolescent Health (49% female; 67% White, 15% Black, 11% Latinx, 6% other [Native American, Asian, or not specified]). In Wave 1 (1994–1995; mean age=16 years), data on 5 psychological assets (optimism, …

Hereditary Angioedema: Diagnosis, Clinical Implications, And Pathophysiology, Evan S. Sinnathamby, Peter P. Issa, Logan Roberts, Haley Norwood, Kevin Malone, Harshitha Vemulapalli, Shahab Ahmadzadeh, Elyse M. Cornett, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing …

Family Income And Cardiovascular Disease Risk In American Adults, Abdul Mannan Khan Minhas, Vardhmaan Jain, Monica Li, Robert W. Ariss, Marat Fudim, Erin D. Michos, Salim S. Virani, Laurence Sperling, Anurag Mehta

Office of the Provost

Socioeconomic status is an overlooked risk factor for cardiovascular disease (CVD). Low family income is a measure of socioeconomic status and may portend greater CVD risk. Therefore, we assessed the association of family income with cardiovascular risk factor and disease burden in American adults. This retrospective analysis included data from participants aged ≥ 20 years from the National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Family income to poverty ratio (PIR) was calculated by dividing family (or individual) income by poverty guidelines specific to the survey year and used as a measure of socioeconomic status. The …