Understanding Of Cardiovascular Disease Research Articles

PL56. Long-term consequences of preeclampsia

Introduction There is a clearly documented increased risk of long-term maternal cardiovascular disease after pregnancy complications such as preeclampsia, premature birth and fetal growth restriction. The risk is highest in pregnancies with both maternal and fetal manifestations of abnormal placentation. We lack today however the mechanistic understanding of the association. We also lack the evidence-based recommendations on how and how frequent to follow up these women at risk, both pre- and postmenopausally. Objective and methods The talk will briefly review the epidemiological associations, with emphasis on cardiovascular disease (CVD) after preeclampsia. In addition, the talk will review common risk factors for preeclampsia and CVD, as women developing preeclampsia may have risk factors in common with older persons developing CVD. Additionally, the talk will suggest how preeclampsia and other placentally-mediated disorders may themselves contribute to an augmented cardiovascular burden that may directly or indirectly affect long-term vascular health. Results Further understanding of the process underlying maternal and placental mediators of preeclampsia may help cast light on development of cardiovascular disease later in life. Further research is needed to ascertain whether specifically targeted group of women with such pregnancy complications benefit from prevention strategies, such as with oral statins or aspirin, similarly to other population groups at risk, and thereby improve long-term maternal health. Conclusion This talk will suggest how longitudinal pregnancy cohorts and biobanks across the world may improve the understanding of CVD in parous women. Options for such studies from pregnancy biobanks within the Global CoLaboratory research network are presented.

Cardiac autoimmunity as a novel biomarker, mediator, and therapeutic target of heart disease in type 1 diabetes.

Patients with type 1 diabetes (T1D) suffer excess mortality from cardiovascular disease (CVD) that has persisted despite substantial reductions in microvascular complications. Although T1D and type 2 diabetes (T2D) are etiologically distinct, it has generally been assumed that CVD in T1D is “the same disease” as that found in T2D. Here, we review the most recent epidemiological and clinical studies on heart disease in T1D, highlighting differences between CVD in T1D and T2D. In addition, we discuss experimental and clinical evidence for a post-myocardial infarction (MI) autoimmune heart syndrome in T1D, including the development of diagnostic assays which we believe can, for the first time, differentiate between heart disease in T1D and T2D. We postulate that a clinically unrecognized form of chronic myocardial inflammation (“myocarditis”) triggered by MI contributes to the poor CVD outcomes in T1D. These findings provide a conceptual shift in our understanding of CVD in T1D and have important diagnostic and therapeutic implications.

Animal Models in Cardiovascular Research: Hypertension and Atherosclerosis.

Hypertension and atherosclerosis are among the most common causes of mortality in both developed and developing countries. Experimental animal models of hypertension and atherosclerosis have become a valuable tool for providing information on etiology, pathophysiology, and complications of the disease and on the efficacy and mechanism of action of various drugs and compounds used in treatment. An animal model has been developed to study hypertension and atherosclerosis for several reasons. Compared to human models, an animal model is easily manageable, as compounding effects of dietary and environmental factors can be controlled. Blood vessels and cardiac tissue samples can be taken for detailed experimental and biomolecular examination. Choice of animal model is often determined by the research aim, as well as financial and technical factors. A thorough understanding of the animal models used and complete analysis must be validated so that the data can be extrapolated to humans. In conclusion, animal models for hypertension and atherosclerosis are invaluable in improving our understanding of cardiovascular disease and developing new pharmacological therapies.

Thirty-year trends in mortality from cardiovascular diseases in Korea.

Background and ObjectivesAn understanding of cardiovascular diseases (CVD) mortality is important for the development of strategies aimed at reducing the burden of CVD. Thus, we examined the changing pattern of CVD mortality in Korea over 30 years (1983-2012) by analyzing the Cause of Death Statistics.Materials and MethodsDeaths from diseases of the circulatory system and those of five CVD categories were analyzed: total heart diseases, acute rheumatic fever/chronic rheumatic heart disease, hypertensive heart disease, ischemic heart disease (IHD) and atherosclerosis. To assess the effects of population ageing on CVD mortality, crude and age-adjusted mortality rates were calculated. Age-adjusted mortality rates were calculated by using the direct standardization method.ResultsOver the 30-year period analyzed in this study, circulatory system disease mortality markedly declined. The age-adjusted mortality rate decreased by 78.5% in men and by 76.3% in women. Consistent decreasing trends were observed for mortalities from rheumatic heart disease, hypertensive heart disease, and atherosclerosis. However, IHD mortality rapidly increased during the 30 years. Crude IHD mortality showed a steady increase until 2007, after which there were fluctuations. But the penalized regression splines showed that crude IHD mortality continued to increase. Age-adjusted IHD mortality peaked in the early 2000s, and started to decrease during the last few years.ConclusionIn summary, total CVD mortality rate has significantly decreased over the 30-year period analyzed in this study but the IHD mortality rate has continuously increased until recently. The prevention and management of cardiovascular diseases amongst the Korean population, especially IHD, still represents a great challenge.

2014 Lucian Award: Jeffrey Robbins.

The 37th Louis and Artur Lucian Award for research in circulatory disease has been presented to Jeffrey Robbins, PhD, of Cincinnati Children’s Hospital Medical Center. Robbins is being honored for 20 continuous years of exceptional cardiovascular research, bolstered by his openness in sharing his materials and findings. Since its beginnings with a $2 million bequest to McGill University in 1965, the Lucian Award has recognized the contributions of active investigators or teams whose work has already had a significant effect on the understanding of cardiovascular disease (Table). In her will, Olga Leibovici established the award to honor her brothers, both engineers, who had died prematurely. The $60 000 CAN prize, the largest given in any biomedical field in Canada, was first awarded in 1978. The Lucian Award places no restrictions on the nationality of recipients, and scientists working in 7 countries have received the honor. The McGill University community and awardees benefit from collaborations that are established or furthered during the 1 or 2 weeks each winner spends at McGill. View this table: Table 1. Previous Recipients of the Lucian Award “Through careful management, this single philanthropic donation from the 1960s has created an incredible legacy that just keeps on giving, and that is something that we will never forget and will protect for the future,” said Jacques Genest, MD, FRCP(C), Professor, Faculty of Medicine at McGill University, current Chair of the Lucian Selection Committee, and Novartis Chair in Medicine, McGill University. Recipients are selected by a volunteer committee of scientists, including many former awardees (see Box, Lucian Award Selection Committee), and each year about 15 top-notch applications make it to the last round. “Robbins has over 20 years of continuous stellar work and his career has led to many unexpected firsts in our understanding of cardiac disease. But what made our decision unanimous was …

Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association.

Despite the known higher risk of cardiovascular disease (CVD) in individuals with type 1 diabetes mellitus (T1DM), the pathophysiology underlying the relationship between cardiovascular events, CVD risk factors, and T1DM is not well understood. Management approaches to CVD reduction have been extrapolated in large part from experience in type 2 diabetes mellitus (T2DM), despite the longer duration of disease in T1DM than in T2DM and the important differences in the underlying pathophysiology. Furthermore, the phenotype of T1DM is changing. As a result of the findings of the Diabetes Control and Complications Trial (DCCT), which compared intensive glycemic control with usual care, and its follow-up observational study, Epidemiology of Diabetes Interventions and Complications (EDIC), intensive management of diabetes mellitus (DM) has become the standard of care and has led to increasing longevity. However, our understanding of CVD in T1DM comes in large part from the previous era of less intensive glycemic control. More intensive glycemic control is associated with significant risk of weight gain, which may be magnified by the obesity epidemic. There is growing interest in better understanding the adverse effects of glycemia, the prevalence and type of lipid abnormalities in T1DM, the prognostic role of albuminuria and renal insufficiency, and the role of blood pressure (BP) in CVD. Obesity-associated metabolic abnormalities such as the proinflammatory state likely modify CVD risk in T1DM; however, the effect may be different from what is seen in T2DM. These concepts, and how they may affect management, have not been fully explored. The present review will focus on the importance of CVD in patients with T1DM. We will summarize recent observations of potential differences in the pathophysiology of T1DM compared with T2DM, particularly with regard to atherosclerosis. We will explore the implications of these concepts for treatment of CVD risk factors in patients with …

Modeling of the acute effects of primary hypertension and hypotension on the hemodynamics of intracranial aneurysms.

Hemodynamics is a risk factor in intracranial aneurysms (IA). Hypertension and pharmacologically induced hypotension are common in IA patients. This study investigates how hypertension and hypotension may influence aneurysmal hemodynamics. Images of 23 IAs at typical locations were used to build patient-specific Computational Fluid Dynamics models. The effects of hypotension and hypertension were simulated through boundary conditions by modulating the normotensive flow and pressure waveforms, in turn produced by a 1D systemic vascular model. Aneurysm location and flow pattern types were used to categorize the influence of hypotension and hypertension on relevant flow variables (velocity, pressure and wall shear stress). Results indicate that, compared to other locations, vertebrobasilar aneurysms (VBA) are more sensitive to flow changes. In VBAs, space-averaged velocity at peak systole increased by 30% in hypertension (16-21% in other locations). Flow in VBAs in hypotension decreased by 20% (10-13% in other locations). Momentum-driven hemodynamic types were also more affected by hypotension and hypertension, than shear-driven types. This study shows how patient-specific modeling can be effectively used to identify location-specific flow patterns in a clinically-relevant study, thus reinforcing the role played by modeling technologies in furthering our understanding of cardiovascular disease, and their potential in future healthcare.

Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association.

Despite the known higher risk of cardiovascular disease (CVD) in individuals with type 1 diabetes mellitus (T1DM), the pathophysiology underlying the relationship between cardiovascular events, CVD risk factors, and T1DM is not well understood. Management approaches to CVD reduction have been extrapolated in large part from experience in type 2 diabetes mellitus (T2DM), despite the longer duration of disease in T1DM than in T2DM and the important differences in the underlying pathophysiology. Furthermore, the phenotype of T1DM is changing. As a result of the findings of the Diabetes Control and Complications Trial (DCCT), which compared intensive glycemic control with usual care, and its follow-up observational study, Epidemiology of Diabetes Interventions and Complications (EDIC), intensive management of diabetes mellitus (DM) has become the standard of care and has led to increasing longevity. However, our understanding of CVD in T1DM comes in large part from the previous era of less intensive glycemic control. More intensive glycemic control is associated with significant risk of weight gain, which may be magnified by the obesity epidemic. There is growing interest in better understanding the adverse effects of glycemia, the prevalence and type of lipid abnormalities in T1DM, the prognostic role of albuminuria and renal insufficiency, and the role of blood pressure (BP) in CVD. Obesity-associated metabolic abnormalities such as the proinflammatory state likely modify CVD risk in T1DM; however, the effect may be different from what is seen in T2DM. These concepts, and how they may affect management, have not been fully explored. The present review will focus on the importance of CVD in patients with T1DM. We will summarize recent observations of potential differences in the pathophysiology of T1DM compared with T2DM, particularly with regard to atherosclerosis. We will explore the implications of these concepts for treatment of CVD risk factors in patients with …

Knowledge of cardiovascular disease in Turkish undergraduate nursing students.

Cardiovascular disease is the number one cause of death worldwide. However, there is not enough data exploring student nurses' understanding, knowledge, and awareness of cardiovascular disease. To investigate knowledge of cardiovascular disease and its risk factors among undergraduate nursing students, with an emphasis on understanding of cardiovascular disease as the primary cause of mortality and morbidity, both in Turkey and worldwide. This cross-sectional survey assessed 1138 nursing students enrolled in nursing schools in Istanbul, Turkey. Data were collected using the Cardiovascular Disease Risk Factors Knowledge Level (CARRF-KL) scale and questions from the Individual Characteristics Form about students' gender, age, level of education, and family cardiovascular health history, as well as smoking and exercise habits. Respondents demonstrated a high level of knowledge about cardiovascular disease, with years of education (p < 0.001), gender (p < 0.001), and high school type (p < 0.05) all significantly associated with CARRF-KL scores. However, more than half of the students were not aware that cardiovascular disease is the primary cause of mortality and morbidity in Turkey and worldwide. The majority of the respondents' body mass index (87%) and waist circumference values (females: 90.3%, males: 94.7%) were in the normal range and most were non-smokers (83.7%). However, more than half of the students did not exercise regularly and had inadequate dietary habits. Although students were knowledgeable about cardiovascular disease and associated risk factors, there were significant gaps in their knowledge; these should be addressed through improved nursing curricula. While students were generally healthy, they could improve their practice of health-promoting behaviors.

Antiplatelet Therapies: Aspirin at the Heart of New Directions

When introduced over 100 years ago, aspirin was prescribed as an analgesic drug to arthritic patients for pain relief. The prevalence of users grew quite rapidly and to this day, aspirin remains widely used in clinical practice. The popularity of aspirin resulted not only from its analgesic properties but also from a second benefit recognized later as an anti-platelet effect. It was this important activity of aspirin that made it one of the most recommended drugs for the treatment and prevention of cardiovascular diseases. The anti-platelet effect of aspirin emerged from the first few case reports published in the early 1900s and was described as a mild bleeding. The molecular mechanisms involved were described in 1971 and constituted the irreversible inhibition of cyclooxygenase-1 enzyme and prevention of platelet aggregation. Today, the contribution of aspirin to our understanding of cardiovascular health persists and remains considerable. Observations from large cohorts of aspirin users generate massive amount of valuable information used in the identification of factors influencing the potential risk for cardiovascular diseases, including sex, age and genetic predisposition. Aspirin and the path of discovery leading to its anti-platelet activity has taken a hundred years was based on manifestations of effects observed in its users, and it remains a successful strategy for the identification of new avenues to treat cardiovascular diseases associated with hyper-platelet activity. The contribution of aspirin to the understanding of cardiovascular diseases and to the design of effective treatment and prevention strategies, remains of high importance in our society.

2013 Lucian Award

The 35th Louis and Artur Lucian Award for research in circulatory disease has been presented to physician scientist David Ginsburg, MD, of the University of Michigan, for his groundbreaking work on blood coagulation and cellular protein processing in cardiovascular diseases. Since its beginnings with a $2 million bequest to McGill University in 1965, the Lucian Award has recognized the contributions of active investigators or teams whose work has already had a significant impact on the understanding of cardiovascular disease (Table). In her will, Olga Leibovici established the award to honor her brothers, both engineers, who had died prematurely. The $60 000 CAN prize, the largest given in any biomedical field in Canada, was first awarded in 1978. The Lucian Award places no restrictions on the nationality of the recipients. The McGill University community and awardees benefit from collaborations that are established or furthered during the time winners spend at McGill. View this table: Table. Previous Recipients of the Lucian Award Recipients are selected by a committee of scientists, approximately half of whom are former awardees, and each year approximately 15 top-notch applications make it to the last round. “It is remarkable how much Ginsburg has transcended, seemingly effortlessly, traditional division and departmental lines in dealing with medicine, vascular biology, and basic molecular biology. His ability to work within a variety of disciplines is what made him the awardee this year,” says Jacques Genest, MD, FRCP(C), Professor, Faculty of Medicine at McGill University, current Chair of the Lucian Selection Committee, and Novartis Chair in Medicine, McGill University. While a postdoctural fellow in the laboratory of Stuart H. Orkin, MD, at Children’s Hospital, Boston, Massachusetts, Ginsburg was inspired by how thoroughly the identification of hemoglobin genes had transformed understanding of the thalassemias. Ginsburg decided to search for the gene for von Willebrand factor (VWF) to better …

Functional Cardiopulmonary Exercise Testing in Potential Renal Transplant Recipients

Functional Cardiopulmonary Exercise Testing in Potential Renal Transplant Recipients

Paradigm shifts in the genetics of inherited arrhythmias: Using next-generation sequencing technologies to uncover hidden etiologies

Long QT syndrome (LQTS), a rare inheritable arrhythmia first described by Romano andWard et al. in the 1960s, is characterized by the prolongation of the QT interval on surface ECGs and an increased risk of potentially fatal ventricular arrhythmias, especially torsade de pointes [1]. In 1995, after years of extensive clinical investigation and linkage analysis, several research groups, including Keating et al., successfully identified three distinct LQTS phenotypes (LQT1, LQT2, and LQT3) associated with mutations in genes encoding plasma membrane ion channels (KCNQ1, KCNH2, and SCN5A, respectively) [2–4]. These seminal studies motivated further extensive genetic screening in LQTS patients using a candidate gene approach and functional analyses of the mutant genes. These efforts provided evidence that ion channel genes represent the genetic basis for several other arrhythmogenic syndromes that occur in the structurally intact heart, often referred to as idiopathic ventricular fibrillation. At present, 13 genes responsible for LQTS have been identified. Approximately 90% of the genotyped LQTS subjects belong to the three major subtypes (LQT1-3) [5] in which numbers of distinct genotype-specific clinical characteristics have been demonstrated, including T-wave morphology [6], triggers for cardiac events [7], response to the epinephrine provocation test [8] and drug therapy [9]. Genetic testing for known arrhythmia susceptibility genes has become the standard-of-care for a number of disorders, including LQTS. Considering the remarkable progress of research in this area, there is no doubt that 1995 was the year in which genetic technologies experienced a paradigm shift with respect to both the understanding and clinical management of inherited arrhythmias. However, it should be noted that despite the rapid progress in understanding the genetic basis, the etiology still remains unknown in approximately 20% of LQTS conditions [10]. Therefore, additional studies are needed to reveal the missing heritable factors associated with these syndromes. Traditionally, DNA sequence information has been elucidated using Sanger sequencing, but this method is limited by the amount of DNA that can be processed at a given time and by the read length (average 800 base pairs). Although the Human Genome Project completed the sequencing of the entire human genome in 2001 using Sanger sequencing, it took 13 years of effort at an estimated cost of $2.7 billion. Now, next-generation sequencing (NGS), a revolutionary new genetic technology, has enabled whole genomes to be sequenced over a period of a few days at projected costs of less than $10,000. This technology involves massively parallel sequencing of clonally amplified or single DNA molecules that are spatially separated in a flow cell. To date, the genes responsible for disease in more than 3000 Mendelian disorders have yet to be identified. NGS opens up exciting new possibilities of discovering the genes associated with these monogenic disorders. Classical strategies involve linkage analysis in families with known shared genetic heritage by identifying candidate genomic regions encompassing the gene

Cardiovascular disease: Prevention and treatment in renal transplant recipients

Abstract Despite improved survival, renal transplant recipients remain at a high risk of increased mortality and mortality from cardiovascular disease. Both traditional cardiovascular disease (CVD) risk factors and those unique to this population add to the burden of disease, making their CVD risk 50 times that of the general population. This article discusses our present understanding of cardiovascular disease, the risk factors, including dyslipidemia, hypertension, allograft rejection and dysfunction, anemia, proteinuria and new onset diabetes after transplantation (NODAT), as well as prevention and management of these risk factors. Cardiovascular interventions as well as future considerations are also briefly discussed.

Proteomics and Metabolomics for Mechanistic Insights and Biomarker Discovery in Cardiovascular Disease

In the last decade, proteomics and metabolomics have contributed substantially to our understanding of cardiovascular diseases. The unbiased assessment of pathophysiological processes without a priori assumptions complements other molecular biology techniques that are currently used in a reductionist approach. In this review, we highlight some of the “omics” methods used to assess protein and metabolite changes in cardiovascular disease. A discrete biological function is very rarely attributed to a single molecule; more often it is the combined input of many proteins. In contrast to the reductionist approach, in which molecules are studied individually, “omics” platforms allow the study of more complex interactions in biological systems. Combining proteomics and metabolomics to quantify changes in metabolites and their corresponding enzymes will advance our understanding of pathophysiological mechanisms and aid the identification of novel biomarkers for cardiovascular disease.

La proteómica y la metabolómica: los mecanismos de la enfermedad cardiovascular y el descubrimiento de biomarcadores

In the last decade, proteomics and metabolomics have contributed substantially to our understanding of cardiovascular diseases. The unbiased assessment of pathophysiological processes without a priori assumptions complements other molecular biology techniques that are currently used in a reductionist approach. In this review, we highlight some of the «omics» methods used to assess protein and metabolite changes in cardiovascular disease. A discrete biological function is very rarely attributed to a single molecule; more often it is the combined input of many proteins. In contrast to the reductionist approach, in which molecules are studied individually, «omics» platforms allow the study of more complex interactions in biological systems. Combining proteomics and metabolomics to quantify changes in metabolites and their corresponding enzymes will advance our understanding of pathophysiological mechanisms and aid the identification of novel biomarkers for cardiovascular disease.Full English text available from:www.revespcardiol.org/en

The Non-coding Road Towards Cardiac Regeneration

Our understanding of cardiovascular disease has evolved rapidly, leading to a number of treatments that have improved patient quality of life and mortality rates. However, there is still no cure for heart failure. This has led to the pursuit of cardiac regeneration to prevent, and ultimately cure, this debilitating condition. To this end, several approaches have been proposed, including activation of cardiomyocyte proliferation, activation of endogenous or exogenous stem/progenitor cells, delivery of de novo cardiomyocytes, and in situ direct reprogramming of cardiac fibroblasts. While these different methodologies are currently being intensely investigated, there are still a number of caveats limiting their application in the clinic. Given the emerging regulatory potential of non-coding RNAs for controlling diverse cellular processes, these molecules may offer potential solutions in this pursuit of cardiac regeneration. In this concise review, we discuss the potential role of non-coding RNAs in a variety of different cardiac regenerative approaches.

Paul Ivan Korner

Paul Korner died on October 3, 2012 after a short illness on the day he was to receive a Lifetime Achievement Award from the International Society of Hypertension in recognition of his contribution to our understanding of cardiovascular disease, particularly hypertension. His legacies include his own original contributions in the field of circulatory control, the work of many esteemed scientists and academics he trained, and his recent monograph: Essential Hypertension and Its Causes. In >330 publications spanning from the 1950s to the present day, he made important contributions in the field of central nervous control of the circulation, particularly baroreflex and chemo reflex function. He studied how structural adaptations are responsible for many characteristics of the hypertension phenotype, developing the concept of the cardiac and vascular amplifier having been influenced by his friend Bjorn Folkow. In many of these fields, he not only introduced new concepts but also methodologies that were taken up by others. Techniques for studying the baroreflex and autonomic versus nonautonomic contributions to peripheral vascular resistance are examples. He was also among the first to understand that reduction of overall risk was the objective in the prevention of coronary heart disease …

Imaginando el futuro del diagnóstico por imagen

Cardiovascular imaging has become essential to achieving a better understanding of cardiovascular diseases. Due to the advent of new technology and the refinement of existing technologies, imaging's role has extended into the biological, functional, and hemodynamic diagnosis of multiple pathophysiologic processes. Current and future trends in cardiovascular imaging will focus on improving early diagnosis of vascular disease, so as to be able to promote cardiovascular health, and on its development as a useful tool in clinical decision-making. Imaging is also increasingly used to quantify the effect of novel therapies. The rapid development of molecular imaging and fusion imaging techniques improves our understanding of cardiovascular processes from the molecular and cellular points of view and makes it possible to design and test new preventive interventions. The proliferation and integration of imaging techniques in different clinical areas and their role in “translational imaging” plays an important part in the implementation of personalized therapeutic and preventive management strategies for patients with cardiovascular disease.Full English text available from:www.revespcardiol.org/en

Imagining the Future of Diagnostic Imaging

Cardiovascular imaging has become essential to achieving a better understanding of cardiovascular diseases. Due to the advent of new technology and the refinement of existing technologies, imaging's role has extended into the biological, functional, and hemodynamic diagnosis of multiple pathophysiologic processes. Current and future trends in cardiovascular imaging will focus on improving early diagnosis of vascular disease, so as to be able to promote cardiovascular health, and on its development as a useful tool in clinical decision-making. Imaging is also increasingly used to quantify the effect of novel therapies. The rapid development of molecular imaging and fusion imaging techniques improves our understanding of cardiovascular processes from the molecular and cellular points of view and makes it possible to design and test new preventive interventions. The proliferation and integration of imaging techniques in different clinical areas and their role in “translational imaging” plays an important part in the implementation of personalized therapeutic and preventive management strategies for patients with cardiovascular disease.