Cardiology Commons^™

Triglyceride-Rich Lipoproteins, Apolipoprotein C-Iii, Angiopoietin-Like Protein 3, And Cardiovascular Events In Older Adults: Atherosclerosis Risk In Communities (Aric) Study, Aliza Hussain, Caroline Sun, Elizabeth Selvin, Vijay Nambi, Josef Coresh, Xiaoming Jia, Christie M Ballantyne, Ron C Hoogeveen

Faculty, Staff and Students Publications

AIMS: Despite statin and antihypertensive therapies, older Americans have high atherosclerotic cardiovascular disease (ASCVD) risk. Novel measures of triglyceride-rich lipoproteins, low-density lipoprotein triglycerides (LDL-TG), and remnant-like particle cholesterol (RLP-C), are associated with ASCVD in middle-aged adults. Polymorphisms in genes encoding angiopoietin-related protein 3 (ANGPTL3) and apolipoprotein C-III (apoC-III), two proteins involved in triglyceride catabolism, are associated with increased risk for hypertriglyceridaemia and ASCVD and are potential therapeutic targets. We examined associations of LDL-TG, RLP-C, apoC-III, and ANGPTL3 levels with ASCVD events in older adults in the Atherosclerosis Risk in Communities (ARIC) study.

METHODS AND RESULTS: In 6359 participants (mean age …

Leveraging Structured And Unstructured Electronic Health Record Data To Detect Reasons For Suboptimal Statin Therapy Use In Patients With Atherosclerotic Cardiovascular Disease, Glenn T. Gobbel, Michael E. Matheny, Ruth R. Reeves, Julia M. Akeroyd, Alexander Turchin, Christie M. Ballantyne, Laura A. Petersen, Salim S. Virani

Office of the Provost

Objective: To determine whether natural language processing (NLP) of unstructured medical text can improve identification of ASCVD patients not using high-intensity statin therapy (HIST) due to statin-associated side effects (SASEs) and other reasons.
Methods: Reviewers annotated reasons for not prescribing HIST in notes of 1152 randomly selected patients from across the VA healthcare system treated for ASCVD but not receiving HIST. Developers used reviewer annotations to train the Canary NLP tool to detect and extract notes containing one or more of these reasons. Negative predictive value (NPV), sensitivity, specificity and Area Under the Curve (AUC) were used to assess accuracy …

Evaluation Of Factors Underlying Sex-Based Disparities In Cardiovascular Care In Adults With Self-Reported Premature Atherosclerotic Cardiovascular Disease, Vardhmaan Jain, Mahmoud Al Rifai, Rodman Turpin, Hatice Nur Eken, Ankit Agrawal, Dhruv Mahtta, Zainab Samad, Stephanie Coulter, Fatima Rodriguez, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

IMPORTANCE: There are limited data regarding sex-based differences in physical and mental health domains and health care access in adults with premature atherosclerotic cardiovascular disease (ASCVD).

OBJECTIVE: To study the association of sex with physical and mental health domains as well as health care access-related factors among adults with self-reported premature ASCVD.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of 748 090 adults aged 18 to 55 years in the Behavioral Risk Factor Surveillance System 2016 to 2019 in the US. Data were analyzed from June to July 2021.

EXPOSURES: Self-reported ASCVD, defined as having a history of coronary artery …

Nutrition, Atherosclerosis, Arterial Imaging, Cardiovascular Risk Stratification, And Manifestations In Covid-19 Framework: A Narrative Review., Smiksha Munjral, Puneet Ahluwalia, Ankush D Jamthikar, Anudeep Puvvula, Luca Saba, Gavino Faa, Inder M Singh, Paramjit S Chadha, Monika Turk, Amer M Johri, Narendra N Khanna, Klaudija Viskovic, Sophie Mavrogeni, John R Laird, Gyan Pareek, Martin Miner, David W Sobel, Antonella Balestrieri, Petros P Sfikakis, George Tsoulfas, Athanasios Protogerou, Prasanna Misra, Vikas Agarwal, George D Kitas, Raghu Kolluri, Jagjit Teji, Mustafa Al-Maini, Surinder K Dhanjil, Meyypan Sockalingam, Ajit Saxena, Aditya Sharma, Vijay Rathore, Mostafa Fatemi, Azra Alizad, Vijay Viswanathan, P K Krishnan, Tomaz Omerzu, Subbaram Naidu, Andrew Nicolaides, Jasjit S Suri

Heart and Vascular Articles

Background: Atherosclerosis is the primary cause of the cardiovascular disease (CVD). Several risk factors lead to atherosclerosis, and altered nutrition is one among those. Nutrition has been ignored quite often in the process of CVD risk assessment. Altered nutrition along with carotid ultrasound imaging-driven atherosclerotic plaque features can help in understanding and banishing the problems associated with the late diagnosis of CVD. Artificial intelligence (AI) is another promisingly adopted technology for CVD risk assessment and management. Therefore, we hypothesize that the risk of atherosclerotic CVD can be accurately monitored using carotid ultrasound imaging, predicted using AI-based algorithms, and reduced …

The Effect Of Untraditional Lipid Parameters In The Development Of Coronary Artery Disease: Atherogenic Index Of Plasma, Atherogenic Coefficient And Lipoprotein Combined Index, Ersin Çelik, Ahmet Rıfkı Çora, Kadir Burhan Karadem

Journal of the Saudi Heart Association

Objective: In this study, we investigated the usability of atherogenic indices of patients who underwent coronary artery bypass surgery (CABG) due to coronary artery disease and patients without CAD as risk factors and markers for cardiovascular disease (CVD). Methods: The data of 150 patients who underwent CABG, and 155 patients who underwent coronary angiography and was not diagnosed with CAD were analysed retrospectively. Demographic data and plasma lipid values were collected. The relationship between these ratios and CVD was investigated via univariate logistic regression analysis performed by creating atherogenic indices. Results: The data of 125 patients who underwent CABG between …

Exome Sequence Association Study Of Levels And Longitudinal Change Of Cardiovascular Risk Factor Phenotypes In European Americans And African Americans From The Atherosclerosis Risk In Communities Study, Elena V Feofanova, Elise Lim, Han Chen, Minjae Lee, Ching-Ti Liu, L Adrienne Cupples, Eric Boerwinkle

Faculty, Staff and Student Publications

Cardiovascular disease (CVD) is responsible for 31% of all deaths worldwide. Among CVD risk factors are age, race, increased systolic blood pressure (BP), and dyslipidemia. Both BP and blood lipids levels change with age, with a dose-dependent relationship between the cumulative exposure to hyperlipidemia and the risk of CVD. We performed an exome sequence association study using longitudinal data with up to 7805 European Americans (EAs) and 3171 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC) study. We assessed associations of common (minor allele frequency > 5%) nonsynonymous and splice-site variants and gene-based sets of rare variants with levels …

Cascade Screening And Treatment Initiation In Young Adults With Heterozygous Familial Hypercholesterolemia., Amy L. Peterson, Matthew Bang, Robert C. Block, Nathan D. Wong, Dean G. Karalis

Division of Cardiology Faculty Papers

Heterozygous familial hypercholesterolemia (HeFH) creates elevated low-density lipoprotein cholesterol (LDL-C), causing premature atherosclerotic cardiovascular disease (ASCVD). Guidelines recommend cascade screening relatives and starting statin therapy at 8-10 years old, but adherence to these recommendations is low. Our purpose was to measure self-reported physician practices for cascade screening and treatment initiation for HeFH using a survey of 500 primary care physicians and 500 cardiologists: 54% "always" cascade screen relatives of an individual with FH, but 68% would screen individuals with "strong family history of high cholesterol or premature ASCVD", and 74% would screen a child of a patient with HeFH. The …

The Role Of Cardiovascular Ct In Occupational Health Assessment For Coronary Heart Disease: An Expert Consensus Document From The Society Of Cardiovascular Computed Tomography (Scct)., Ahmad M Slim, Emilio Fentanes, Michael K Cheezum Md, Iain T Parsons, Christopher Maroules, Billy Chen, Suhny Abbara, Kelley Branch, Prashant Nagpal, Nishant R Shah, Dustin M Thomas, Todd C Villines, Ron Blankstein, Leslee J Shaw, Matthew Budoff, Ed Nicol

Parkview Heart Institute

No abstract provided.

High Burden Of Subclinical And Cardiovascular Disease Risk In Adults With Metabolically Healthy Obesity: The Atherosclerosis Risk In Communities (Aric) Study, Yvonne Commodore-Mensah, Mariana Lazo, Olive Tang, Justin B Echouffo-Tcheugui, Chiadi E Ndumele, Vijay Nambi, Dan Wang, Christie Ballantyne, Elizabeth Selvin

Faculty, Staff and Students Publications

OBJECTIVE: It is controversial whether adults who are obese but "metabolically healthy" have cardiovascular disease (CVD) risk comparable with that of normal-weight adults. High-sensitivity cardiac troponin T (hs-cTnT), a biomarker of myocardial damage, is useful in characterizing subclinical CVD. We categorized obesity phenotypes and studied their associations with subclinical and clinical CVD and CVD subtypes, including heart failure (HF).

RESEARCH DESIGN AND METHODS: We conducted cross-sectional and prospective analyses of 9,477 adults in the Atherosclerosis Risk in Communities (ARIC) study. We used the Adult Treatment Panel III criteria and BMI to define obesity phenotypes as follows: metabolically healthy normal weight, …

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne

Faculty, Staff and Students Publications

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels …

Effects Of Endogenous Angiotensin Ii On Abdominal Aortic Aneurysms And Atherosclerosis In Angiotensin Ii-Infused Mice, Masayoshi Kukida, Hisashi Sawada, Satoko Ohno-Urabe, Deborah A. Howatt, Jessica J. Moorleghen, Marko Poglitsch, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

No abstract provided.

Nanoanalytical Analysis Of Bisphosphonate-Driven Alterations Of Microcalcifications Using A 3d Hydrogel System And In Vivo Mouse Model, Jessica L. Ruiz, Joshua D. Hutcheson, Luis Cardoso, Amirala Bakhshian Nik, Alexandra Condado De Abreu, Tan Pham, Fabrizio Buffolo, Sara Busatto, Stefania Frederici, Andrea Ridolfi, Masanori Aikawa, Sergio Bertazzo, Paolo Bergese, Sheldon Weinbaum, Elena Aikawa

Publications and Research

Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE−/− mouse was used …

Prevalence Of Cardiovascular Risk Factors In A Nationally Representative Adult Population With Inflammatory Bowel Disease Without Atherosclerotic Cardiovascular Disease, Tanushree Agrawal, Isaac Acquah, Amit K. Dey, Kerri Glassner, Bincy Abraham, Ron Blankstein, Salim S. Virani, Michael J. Blaha, Javier Valero-Elizondo, Nehal Mehta

Office of the Provost

Background and aims: Chronic inflammation is associated with premature atherosclerotic cardiovascular disease (ASCVD). We studied the prevalence of cardiovascular risk factors (CRFs) amongst individuals with IBD who have not developed ASCVD.
Methods: Our study population was derived from the 2015 - 2016 National Health Interview Survey. Those with ASCVD (defined as myocardial infarction, angina or stroke) were excluded. The prevalence of CRFs among individuals with IBD was compared with those without IBD. The odds CRFs among adults with IBD was assessed using logistic regression models.
Results: In our study population of 60,155 individuals, 786 (1.3%) had IBD. IBD was associated …

Distribution Of Calcium Volume, Density, Number, And Type Of Coronary Vessel With Calcified Plaque In South Asians In The Us And Other Race/Ethnic Groups: The Masala And Mesa Studies, Mahmoud Al Rifai, Alka M Kanaya, Namratha R Kandula, Miguel Cainzos-Achirica, Jaideep Patel, Matthew Budoff, Michael H Criqui, Michael J Blaha, Salim S Virani

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: South Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD) events than non-Hispanic whites (NHW) and several other Asian groups. The coronary artery calcium (CAC) Agatston score may not capture the unique characteristics of coronary plaque in SA. We therefore evaluated the prevalence and patterns of advanced CAC measures (specific coronary vessel involvement, CAC volume and density) in SA versus other race/ethnicities.

METHODS: We combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We used multivariable-adjusted linear regression models to compare advanced CAC …

Patient-Perceived Versus Actual Risk Of Cardiovascular Disease And Associated Willingness To Consider And Use Prevention Therapy, Ann Marie Navar, Tracy Y Wang, Shuang Li, Xiaojuan Mi, Zhuokai Li, Jennifer G Robinson, Salim S Virani, Eric D Peterson

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy.

METHODS: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient …

The Role Of Microbiologic Agents In The Progression Of The Atherosclerosis: A Comprehensive Review, Ahmet Karabulut

Journal of the Saudi Heart Association

Atherosclerosis is a leading cause of disability, morbidity and mortality in the world. Atherosclerosis is accepted as a chronic progressive inflammatory disease. The inflammatory cascade in the vascular wall is well-defined. However, the predictors and contributors of the inflammatory response in atherosclerosis are not completely understood. Systemic and local inflammation, which enhance the burden of inflammation in the vascular wall, have been proposed as risk factors for the progression of atherosclerosis. Infectious micro-organisms are one of the major triggering factors for local and systemic inflammation. In this review, we aimed to emphasize the linkage between micro-organisms and the progression of …

When Myocardial Infarction Is Choosing Young Victims, Cristina Nedelcu, Mihaela Ionescu, Paris Ionescu, Vitalie Morosanu, Gabriel Smarandache, Dumitru Cristinel Badiu, Florentina Gherghiceanu, Vlad Denis Constantin, Emanuele Maria Merlo, Daniel Niţă

Journal of Mind and Medical Sciences

We present the case of a 31-year-old patient, without cardiovascular risk factors, without significant pathological or family history of cardiovascular disease, who was diagnosed with severe coronary artery disease, left main bifurcation localization, which required surgical coronary revascularization. The angiographic and intraoperative aspect excluded the most common causes of non-atherosclerotic causes of coronary lesions. Vasculitis was another possible etiology but was also excluded based on the normal clinical examination, negative inflammation markers, lack of diffuse vascular impairment, TPHA and negative VDRL. Prolonged mental stress can lead to accelerated progression of atherosclerosis by inducing endothelial dysfunction, our patient describing a “burnout …

Effect Of Coronary Artery Bifurcation Angle On Atherosclerotic Lesion Localization Distance To The Bifurcation Site, Murat Ziyrek, Ahmet Lütfü Sertdemir, Mustafa Duran

Journal of the Saudi Heart Association

Objectives: Although percutaneous coronary interventions become a common treatment modality for coronary artery diseases, lesion localization make these procedures more complex. As the lesion localizes near to the bifurcation site, more complex PCI procedures, overqualified equipments are needed and complication risk increases. Previous studies have demonstrated the strong correlation between wide angulation and significant coronary stenosis. However, a paucity of data exists about the association between bifurcation angle and lesion localization distance. In this study we analysed the effect of coronary bifurcation angle and left main coronary artery length on the atherosclerotic lesion localization.

Methods: Patients, who underwent coronary angiography …

Penetrating Atherosclerotic Ulcer Of The Ascending Aorta Found Incidentally In A 71-Year-Old Man, Antonino M Grande, Dario Di Perna, Adele Valentini, Eloisa Arbustini

The Texas Heart Institute Journal

No abstract provided.

Serum Tumor Necrosis Factor-Alpha Associates With Myocardial Oxygen Demand And Exercise Tolerance In Postmenopausal Women, Stephen J. Carter, David R. Bryan, William H. Neumeier, Stephen P. Glasser, Gary R. Hunter

Internal Medicine Faculty Publications

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO_2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest …

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …

Cigarette Smoking And Cardio-Renal Events In Patients With Atherosclerotic Renal Artery Stenosis., Christopher A Drummond, Pamela S Brewster, Wencan He, Kaili Ren, Yanmei Xie, Katherine Tuttle, Steven T Haller, Kenneth Jamerson, Lance D Dworkin, Donald E Cutlip, Timothy P Murphy, Ralph B D'Agostino, William L Henrich, Jiang Tian, Joseph I Shapiro, Christopher J Cooper

Articles, Abstracts, and Reports

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p

Population-Based Cohort Study In Outcome Of Phased Progression Of Atherosclerosis In China (Persuade): Objective, Rationale And Design, Dong-Kai Shan, Yong Zhou, You-Xin Wang, Xiang Gao, Wei Wang, Jun-Jie Yang, Yun-Dai Chen

Research outputs 2014 to 2021

The coronary artery calcification score and pericardial fat volume have recently been reported to be strongly associated with the severity and presence of coronary atherosclerosis. However, no studies have explored the outcome of phased progression of atherosclerosis by non-contrast computed tomography in asymptomatic people in China. The population-based cohort study in outcome of phased progression of atherosclerosis in China (PERSUADE), an observational, longitudinal and prospective cohort study in a target population of healthy subjects based in Jidong Oilfield (China), prospectively analyzes the outcome of phased progression of atherosclerosis by non-contrast computed tomography in healthy population. The results of this study …

Structure And Functions Of Angiotensinogen, Hong Lu, Lisa A. Cassis, Craig W. Vander Kooi, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the sole precursor of all angiotensin peptides. Although AGT is generally considered as a passive substrate of the renin–angiotensin system, there is accumulating evidence that the regulation and functions of AGT are intricate. Understanding the diversity of AGT properties has been enhanced by protein structural analysis and animal studies. In addition to whole-body genetic deletion, AGT can be regulated in vivo by cell-specific procedures, adeno-associated viral approaches and antisense oligonucleotides. Indeed, the availability of these multiple manipulations of AGT in vivo has provided new insights into the multifaceted roles of AGT. In this review, the combination of …

Longitudinal Changes In Vascular Risk Markers And Mortality Rates Among A Latino Population With Hypertension, Matthew C Pflederer, Carlin S Long, Brenda Beaty, Edward P Havranek, Philip S Mehler, Angela Keniston, Mori J Krantz

The Texas Heart Institute Journal

Vascular markers such as pulse-wave velocity and carotid intima-media thickness (CIMT) might improve the prediction of incident cardiovascular disease beyond traditional risk factors. These vascular markers have not been well characterized in minority populations and might be more useful than inflammatory biomarkers. We conducted a prospective, longitudinal cohort study among hypertensive patients in an urban safety-net hospital. We evaluated inflammatory biomarkers, arterial pulse-wave velocity, and carotid intima-media thickness at baseline, 1 year, and 2 years. The primary outcome variable was CIMT. Generalized linear mixed-effects models were used to evaluate associations between CIMT and predictive variables accounting for the correlation of …

Infusion Of Reconstituted High-Density Lipoprotein, Csl112, In Patients With Atherosclerosis: Safety And Pharmacokinetic Results From A Phase 2a Randomized Clinical Trial, Pierluigi Tricoci, Denise M. D'Andrea, Paul A. Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A. Blazing, Louis Cannon, Alison L. Bailey, Dominick J. Angiolillo, Andreas Gille, Charles L. Shear, Samuel D. Wright, John H. Alexander

Gill Heart & Vascular Institute Faculty Publications

Background CSL112 is a new formulation of human apolipoprotein A‐I (apoA‐I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double‐blind, multicenter, dose‐ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.

Methods and Results Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2‐hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug–related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA‐I plasma …

Ultrasound Biomicroscopic Imaging For Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis And Markers Of Inflammation In Atherosclerotic Development In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Yan Sun, Qin Wang, Jiao Yang, Ya Yang, Li Song, Zheng Wang, Xiang-Hong Luo, Rui-Juan Su

The Texas Heart Institute Journal

We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis.

We divided IL-1Ra+/−/apolipoprotein-E (apoE)−/− and IL-1Ra+/+/apoE−/− mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra+/+/apoE+/+ mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and …

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …

Components Of The Complete Blood Count As Risk Predictors For Coronary Heart Disease: In-Depth Review And Update, Mohammad Madjid, Omid Fatemi

The Texas Heart Institute Journal

Atherosclerosis is an inflammatory disease, and several inflammatory biomarkers, such as C-reactive protein, have been used to predict the risk of coronary heart disease. High white blood cell count is a strong and independent predictor of coronary risk in patients of both sexes, with and without coronary heart disease. A high number of white blood cells and their subtypes (for example, neutrophils, monocytes, lymphocytes, and eosinophils) are associated with the presence of coronary heart disease, peripheral arterial disease, and stroke. The coronary heart disease risk ratios associated with a high white blood cell count are comparable to those of other …