Author Interviews, Genetic Research, Heart Disease, Nature / 14.06.2024

MedicalResearch.com Interview with: Ben Omega Petrazzini, B.Sc. Associate Bioinformatician Ron Do Laboratory Ron Do, Ph.D. Professor, Department of Genetics and Genomic Sciences Director, Center for Genomic Data Analytics Associate Director in Academic Affairs, The Charles Bronfman Institute for Personalized Medicine Charles Bronfman Professor in Personalized Medicine Icahn School of Medicine at Mount Sinai     MedicalResearch.com: What is the background for this study? Response: Rare coding variants directly affect protein function and can inform the role of a gene in disease. Discovery of rare coding variant associations for coronary artery disease (CAD) to date have only had limited success. Genetic studies typically use standard phenotyping approaches to classify cases versus controls for CAD. However, this phenotyping approach doesn’t capture disease progression or severity in individuals. We recently introduced an in-silico score for CAD (ISCAD) that tracks CAD progression, severity, underdiagnosis and mortality (Forrest et al. The Lancet, 2023, PMID 36563696). ISCAD was built using a machine learning model trained on clinical data from electronic health records (EHR). Importantly, ISCAD is a quantitative score that measures CAD on a spectrum. The quantitative nature of the score provides an opportunity to discover additional rare coding variant associations that may not have been detected with the standard case-control phenotyping approach. Here in this study, we performed a large-scale rare variant association study in the exome sequences of 604,915 individuals for ISCAD, a machine learning-based score for CAD. (more…)
Author Interviews, Erectile Dysfunction, Heart Disease, JACC, Karolinski Institute / 10.04.2021

MedicalResearch.com Interview with: Martin J Holzmann MD PhD Department of Emergency Medicine Karolinska University Hospital Stockholm, Sweden  MedicalResearch.com: What is the background for this study? What are the main findings? Response: ​We published a paper 2007 in Heart where we showed that PDE5i lower mortality in men with a recent myocardial infarction. With this study we wanted to investigate if PDE5i led to a beneficial outcome in men with stable coronary artery disease. (more…)
Author Interviews, Heart Disease, JACC / 17.11.2020

MedicalResearch.com Interview with: Simon Winther, MD, PhD Associate professor Department of Cardiology, Gødstrup Hospital Herning, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Both European and American guidelines have traditionally recommended estimating the pre-test probability (PTP) of CAD based on the classic Diamond-Forrester approach using sex, age, and type of chest complaints. However, The European Society of Cardiology (ESC) has recently suggested a novel concept of Clinical Likelihood of CAD as a more comprehensive assessment of CAD probability but no strategy has been proposed. I this study, we improve the estimation of the likelihood of obstructive coronary artery disease (CAD) by combining the classic pre-test probability model (Diamond–Forrester approach using sex, age, and symptoms) with clinical risk factors and coronary artery calcium score in symptomatic patients with suspected CAD. Hence, we propose a simple clinical tool for the individual estimation of clinical likelihood of CAD. The tool was developed by stepwise simplification of advanced machine learning models without significant loss of accuracy and the model were validated the both European and North American cohorts.  (more…)
Author Interviews, Emory, Heart Disease / 13.09.2019

MedicalResearch.com Interview with: Viola Vaccarino, MD, PhD Wilton Looney Professor and Chair in Cardiovascular Research Dept. of Epidemiology, Rollins School of Public Health Professor, Dept. of Medicine, School of Medicine Emory University MedicalResearch.com: What is the background for this study? Response: Psychological stress has been linked to increased risk for cardiovascular disease. The mechanisms have not been clear. One hypothesis has been that chronic or repeated exposure to psychological stress can cause a phenomenon of “wear-and-tear” of the vascular system due to activation of the neuroendocrine stress systems, eventually leading to accelerated plaque formation and adverse cardiovascular events. However, this has never been demonstrated in humans. In some individuals, psychological stress can induce a transitory impairment of the endothelium, a phenomenon known as endothelial dysfunction. A healthy endothelium is essential in blood flow regulation and in maintaining cardiovascular health. (more…)
Author Interviews, Cleveland Clinic, Heart Disease, JACC, Surgical Research / 22.11.2018

MedicalResearch.com Interview with: Peter Hu MD Cleveland ClinicPeter T. Hu MD Department of Cardiology Cleveland Clinic MedicalResearch.com: What is the background for this study? What are the main findings? Response: Among patients with blockages in multiple coronary vessels, we studied predictors and outcomes of having a staged versus one-time multivessel percutaneous coronary intervention. By "staged" we mean performing coronary intervention only on one vessel, letting the patient recover, and fixing the other blockages at a later date. We know that multivessel coronary artery disease is very common - present in up to 2/3 of patients who require coronary interventions. Previous studies in patients with STEMI (ST-elevation myocardial infarction) suggested that staged multivessel PCI was associated with lower risk of death compared with one-time multivessel revascularization. Outside of STEMI patients, very little data exist in a broader group of patients who undergo coronary interventions to multiple vessels. In our study, we found an association between doing a staged PCI and lower long-term mortality benefit compared with fixing multiple blockages at once. What was surprising was there seemed to be a correlation with the degree of benefit from staged PCI based on the symptoms and signs the patient presented with. The association with improved outcomes was strongest in patients with STEMI, followed by those with NSTEMI, unstable angina, and stable angina, respectively. We also found that the decision to perform staged PCI was driven by patient and procedural characteristics, as well as other unmeasured site variation.  (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA / 06.04.2018

MedicalResearch.com Interview with: Stella Aslibekyan, PhD Associate Professor PhD Program Director Department of Epidemiology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: When the human genome was sequenced in 2003, there were somewhat unrestrained expectations of unraveling all etiologic mysteries and discovering breakthrough treatments. Needless to say, that did not happen, in part because individual genetic variants can only account for a small fraction of trait variability. Since then, epigenetics-- the study of mitotically heritable changes in gene expression-- has emerged as another promising avenue for understanding disease risk. The best studied epigenetic process in humans is DNA methylation, and earlier studies (including some from our group) have shown interesting associations between changes in methylation in specific genomic regions and cardiovascular disease traits, e.g. plasma cholesterol levels. In this project, we have combined DNA methylation data on thousands of individuals from multiple international cohorts and interrogated epigenetic contributions to circulating tumor necrosis factor alpha (TNFa), a marker of systemic inflammation. We identified and replicated several epigenomic markers of TNFa, linked them to variation in gene expression, and showed that these methylation changes (which were located in interferon pathway genes) were predictive of coronary heart disease later in life. Interestingly, the variants we discovered were not sequence-dependent (in other words, they were not associated with any genetic mutations), highlighting the role of the environment. (more…)
Author Interviews, Geriatrics, Heart Disease, Personalized Medicine, UCLA / 12.12.2017

MedicalResearch.com Interview with: Joseph A. Ladapo, MD, PhD Principal Substudy Investigator, PRESET Registry Subgroup Analysis, Elderly Patients Associate Professor, Division of General Internal Medicine and Health Services Research David Geffen School of Medicine University of California, Los Angeles MedicalResearch.com: What is the background for this study?  Response: The mapping of the Human Genome 14 years ago ushered in a new era of precision medicine. Many people are familiar with advances in oncology using precision medicine, but recently, new developments in precision medicine in cardiology have allowed us to develop a tool to differentiate patients likely to have obstructive coronary artery (CAD) from those who have non-cardiac causes of their symptoms. Diagnosing CAD in the elderly is challenging. Aging individuals often present with atypical symptoms of CAD which can complicate the evaluation process. The typical diagnostic pathway for possible CAD often starts with less invasive testing and progresses to invasive testing, especially in older patients. Invasive procedures pose greater risk in the elderly population than they do in younger patients because of the higher risk of side effects, including bleeding, vascular complications and kidney injury. Elderly adults evaluated for CAD have a higher pretest probability of CAD and are also at higher risk of experiencing procedure-related complications during their evaluation.[i],[ii] It is also important to note that elderly patients are often underrepresented in clinical trials and other types of comparative effectiveness research.[iii],[iv] For example, the 2013 American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease Risk Algorithm is only formally approved to be used in individuals up to the age of 75, despite the fact that individuals exceeding this threshold in age experience higher rates of adverse cardiovascular events.[v] All of this means that the elderly population may have the most to gain from timely and accurate determination of their currently likelihood of obstructive CAD. This precision medicine tool, the age, sex and gene expression score (ASGES), and its clinical utility in the elderly population is the focus of this study. It was based on patient data from the PRESET Registry, a prospective, multicenter, observational study enrolling stable, symptomatic outpatients from 21 U.S. primary care practices from August 2012 to August 2014. (more…)
Author Interviews, Heart Disease, Surgical Research / 20.04.2017

MedicalResearch.com Interview with: Emmanouil S. Brilakis, MD, PhD Director, Center for Advanced Coronary Interventions Minneapolis Heart Institute Minneapolis, Minnesota 55407 Adjunct Professor of Medicine University of Texas Southwestern Medical School at Dallas MedicalResearch.com: What is the background for this study? What are the main findings? Response: Calcification in the coronary arteries might hinder lesion crossing, equipment delivery and stent expansion and contribute to higher rates of in-stent restenosis, as well as stent thrombosis. In this project we sought to examine the impact of calcific deposits on the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in a contemporary, multicenter registry. We analyzed the outcomes of 1,476 consecutive CTO PCIs performed in 1,453 patients between 2012 and 2016 at 11 US centers. Data collection was performed in a dedicated online database (PROGRESS CTO: Prospective Global Registry for the Study of Chronic Total Occlusion Intervention, Clinicaltrials.gov Identifier: NCT02061436). (more…)
Author Interviews, Heart Disease, JACC, Medical Imaging, MRI / 19.04.2017

MedicalResearch.com Interview with: Pr. Juerg Schwitter MD Médecin Chef Cardiologie Directeur du Centre de la RM Cardiaque du CHUV Centre Hospitalier Universitaire Vaudois - CHUV Suisse  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Coronary artery disease (CAD) is still one of the leading causes of death in the industrialized world and as such, it is also an important cost driver in the health care systems of most countries. For the European Union, the estimated costs for CAD management were 60 billion Euros in 2009, of which approximately 20 billion Euros were attributed to direct health care costs (1). In 2015, the total costs of CAD management in the United States were estimated to be 47 billion dollars (2). Substantial progress has been achieved regarding the treatment of CAD including drug treatment but also revascularizations procedures. There exists a large body of evidence demonstrating myocardial ischemia as one of the most important factors determining the patient’s prognosis and reduction of ischemia has been shown to improve outcome. On the other hand, techniques to detect CAD, i.e. relevant myocardial ischemia, were insufficient in the past. Evaluation of myocardial perfusion by first-pass perfusion cardiac magnetic resonance (CMR) is now closing this gap (3) and CMR is recommended by most international guidelines for the work-up of known or suspected CAD (4,5). Still, a major issue was not clarified until now, i.e. “how much ischemia is required to trigger revascularization procedures”. Thus, this large study was undertaken to assess at which level of ischemia burden, patients can be safely deferred from revascularization and can be managed by risk factor treatment only. Of note, this crucial question was addressed in both, patients with suspected CAD but also in patients with known (and sometimes already advanced) CAD, thereby answering this question in the setting of daily clinical practice. (more…)
Annals Internal Medicine, Author Interviews, Heart Disease, Outcomes & Safety / 11.03.2015

MedicalResearch.com Interview with: Harindra C. Wijeysundera MD PhD FRCPC Interventional Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre Scientist, Sunnybrook Research Institute (SRI) Assistant Professor, Dept. of Medicine & Institute of Health Policy, Management and Evaluation University of Toronto Adjunct Scientist, Institute for Clinical Evaluative Sciences (ICES) Toronto, ON, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Wijeysundera: Given the rapid increase in health care costs, there has been growing emphasis on the more rational use of resources.  One such effort is the development of appropriate use  criteria.  Such criteria have been developed in many areas of medicine, including in cardiology for diagnostic angiography.  The underlying rationale for a test to be appropriate is that its anticipated benefit outweighs its anticipated harms.  However, there is a paucity of empirical evidence validating this conceptual framework. Our goal was to validate the 2012 appropriate use criteria for diagnostic coronary angiography, by examining the relationship between the appropriateness of a coronary angiography in patients with suspected stable ischemic heart disease and the proportion of patients who were found to have obstructive coronary artery disease.  We used data obtained from the Cardiac Care Network registry of Ontario, Canada.  This is a population based registry of all cardiac procedures in the province of Ontario.  We examined 48,336 patients and found that 58.2% of angiographic studies were classified as appropriate, 10.8% were classified as inappropriate, and 31.0% were classified as uncertain. Overall, 45.5% of patients had obstructive CAD. In patients with appropriate indications for angiography, 52.9% had obstructive CAD, with 40.0% undergoing revascularization. In those with inappropriate indications, 30.9% had obstructive CAD and 18.9% underwent revascularization; in those with uncertain indications, 36.7% had obstructive CAD and 25.9% had revascularization. Although more patients with appropriate indications had obstructive CAD and underwent revascularization (P < 0.001), a substantial proportion of those with inappropriate or uncertain indications had important coronary disease.  Our conclusion was that despite the association between appropriateness category and obstructive CAD, this study raises concerns about the ability of the appropriate use  criteria to guide clinical decision making. (more…)
Author Interviews, Heart Disease, JACC / 15.10.2014

Nils P. Johnson, M.D., M.S. Assistant Professor - Cardiovascular Medicine Department of Internal Medicine University of Texas Health Science Center Houston TexasMedicalResearch.com Interview with Nils P. Johnson, M.D., M.S. Assistant Professor - Cardiovascular Medicine Department of Internal Medicine University of Texas Health Science Center Houston Texas Medical Research: What are the main findings of the study? Dr. Johnson: Our study had 3 main findings.
  • First, the numeric fractional flow reserve (FFR) value related continuously to risk, such that clinical events increased as FFR decreased and revascularization showed larger net benefit  for lower baseline FFR values.
  • Second, fractional flow reserve measured immediately after  stenting also showed an inverse relationship with prognosis, likely due to its relationship with diffuse disease.
  • Third, an fractional flow reserve-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. (more…)
AHA Journals, Author Interviews, Biomarkers, Heart Disease / 08.08.2014

MedicalResearch.com Interview with: Rakesh K. Mishra, MD San Francisco Veterans Affairs Medical Center San Francisco, CA 94121. Medical Research: What are the main findings of the study? Dr. Mishra: Increased levels of both BNP and NT-proBNP are associated with elevated risk of adverse cardiovascular events in patients with stable coronary artery disease. However, when added to existing clinical models of risk, NT-proBNP is superior to BNP for risk reclassification. (more…)
Author Interviews, Heart Disease, Vitamin D / 14.02.2014

Eirik Magnus Meek Degerud Department of Clincal Medicine University of BergenMedicalResearch.com Interview with:  Eirik Magnus Meek Degerud Department of Clincal Medicine University of Bergen MedicalResearch.com: What are the main findings of the study? Answer: That among patients with established coronary artery disease there was no observable relationship between the amount of vitamin D circulating in their blood and the extent of disease progression during the following year. (more…)
Author Interviews, Diabetes, Genetic Research, Heart Disease, JAMA / 28.08.2013

Lu Qi, MD, PhD, FAHA Assistant Professor of Medicine Harvard Medical School Assistant Professor of Nutrition Harvard School of Public HealthMedicalResearch.com Interview with: Lu Qi, MD, PhD, FAHA Assistant Professor of Medicine Harvard Medical School Assistant Professor of Nutrition Harvard School of Public Health

MedicalResearch.com: What are the main findings of the study? Answer: The main findings include, we for the first time identified a genetic variant predisposing to high risk of coronary heart disease in patients with type 2 diabetes, using genome-wide association (GWA) approach. More interesting, we demonstrated that the variant may affect expression of a gene involved in metabolism of amino acid glutamic acid, which has been related to insulin secretion and heart health in previous studies. (more…)
Author Interviews, Blood Pressure - Hypertension, Heart Disease / 20.08.2013

Dr. Anthony Bavry, MD MPH Interventional Cardiology Assistant Professor of Medicine University of Florida 1600 SW Archer Road Gainesville, FL 32610MedicalResearch.com Interview with Dr. Anthony Bavry, MD MPH Interventional Cardiology Assistant Professor of Medicine University of Florida 1600 SW Archer Road Gainesville, FL 32610 MedicalResearch.com: What are the main findings of the study? Dr. Bavry: Among individuals with chronic stable coronary artery disease, it is possible to define a group who are at relatively low risk for adverse cardiovascular events. MedicalResearch.com:Were any of the findings unexpected? (more…)