How I Healed my Heart Disease

Your Heart and Nutrition

Your Heart and Nutrition

Prevention is better than a cure. Learn how to cherish your heart by taking the necessary means to keep it pumping healthily and steadily through your life.

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Natural Secrets For Healing Your Heart

This eBook is devoted to exposing the secrets that cardiologists and surgeons don't want you to know, and how to take control of your own heart and heal yourself. Eight out of every ten coronary bypasses will not actually help the patient. So why risk being in the 80% that will get no benefit from a bypass? Learn to heal your own heart and keep yourself healthy with this eBook guide. Bob Livingston has poured years of research into his findings, and is now sharing the methods that he has developed from careful, methodical research that the medical industry would never allow. It would make them go bankrupt! You will learn what supernutrient doctors don't want you to know about, and how to make an all-natural, chemical and drug-free blood thinner And even more information that doctors don't want revealed to the public. You don't have to be one of the 70% of Americans diagnosed with heart disease. You can heal your heart!

Natural Secrets For Healing Your Heart Overview

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Introduction diet and cardiovascular disease

Cardiovascular disease (CVD) is still a major cause of death in Western populations and is becoming an important cause of morbidity and mortality worldwide. Thanks to advanced medical knowledge and treatments, many patients survive an initial event. Because of that, prevention of secondary CVD is a growing task for nutritionists and other health professionals. Cardiovascular risk can be reduced by lifestyle changes, one of which is diet. There is now substantial evidence from epidemiological and clinical studies that a diet rich in fruits, vegetables, unrefined grains, fish and low-fat dairy products, and low in saturated fats and sodium, can reduce the risk of coronary heart disease and hypertension.1 People who have adopted such diets have benefited by way ofamuch lower risk of heart disease (see Table 1.1).1-4 However, such a prudent diet is not typical of what consumers in Western countries eat.3 5 It appears that consumers today are less likely to invest in long-term health if...

Coronary Heart Disease

Based on their review of 43 studies that examined the relationship between physical inactivity and CHD incidence, Powell and colleagues (1987) concluded that the risk of incident CHD due to physical inactivity ranges from 1.5 to 2.4 (median 1.9). These values are similar in magnitude to other CHD risk factors, such as hypertension, hypercholesterolemia, and smoking. These data are consistent with recent evidence from the Nurses Health Study, in which physical inactivity (< 1 h of exercise per week) was found to be associated with increased risk (RR 1.58 95 CI, 1.39-1.80) of incident coronary heart disease in 88,393 women followed for 20 years (Li et al, 2006). Data from the Womens' Health Study also indicate that the health benefits of physical activity are not limited to vigorous activity, such that participating in light to moderate physical activity, such as walking for at least 1 h per week, is associated with lower CHD risk (RR 0.49 95 CI, 0.28-0.86) (Leeetal, 2001).

Federally Funded Research on Heart Disease

Government supports a variety of research studies relating to heart disease. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to heart disease. animals or simulated models to explore heart disease. The following is typical of the type of information found when searching the CRISP database for heart disease

Project Title 3D Myocardial Strain Vectors In Ischemic Heart Disease

Summary (provided by applicant) Directed intervention (coronary artery bypass surgery intra-coronary stent placement) in the treatment of coronary artery disease is costly in patient morbidity, mortality and U.S. health care dollars. Methodologies that can improve the accuracy of application of these modalities deserve aggressive investigation. Magnetic Resonance Imaging (MRI) combined with radiofrequency tissue-tagging can non-invasively lay down transmural crosshatched grids in the myocardium that can be tracked throughout the cardiac cycle by MRI. Computer-based analysis techniques, developed in our laboratory, can track the grid intersections and generate regional point displacements and transmural 3D myocardial strain maps. Strain is a normalized description of direction and degree of myocardial point movement. From these 3D strain maps we can determine the direction of principal strain vectors at every point throughout the left ventricle. We hypothesize, based on our preliminary...

Cardiovascular Diseases

Similar considerations apply to the relationship (if any) between myocardial infarction and ephedrine use. The report by Cockings and Brown described a 25-year-old drug abuser who injected himself with an unknown amount of cocaine intravenously (120). The only other published reports involved a woman in labor who was receiving other vasoactive drugs (121) and two pseudoephedrine users, one of whom was also taking bupropion, who developed coronary artery spasm (122,123). Three cases of ephedra-related coronary spasm in anesthetized patients have also been reported, but multiple agents were administred in all three cases, and the normal innervation of the coronary arteries was disrupted in two of the cases where a high spinal anesthetic had been administered (121,124). One case of alleged ephedrine-re-lated hypersensitivity myocarditis has been reported (125), but the patient was taking many other herbal supplements, and the responsible agent is not known with certainty. Although there...

Project Title Bridging Genes And Heart Disease In Downs Syndrome

Summary Down syndrome (DS) is a major cause of congenital heart disease (CHD), of which most is related to defective morphogenesis of the endocardial cushions ( EC). Although the embryologic processes underlying cushion morphogenesis are elegantly described, the signalling pathways that lead from genes to defects are largely unknown. The ultimate goal of the research described in this proposal is to define the gen(s) responsible for DS-CHD, to define its role in cushion morphogenesis and to provide models in which to modify its expression. Previous work by this group has defined a DS-CHD region based on human and mouse models and has generated a sequence ready contig, with 300 kb of finished sequence and the remainder by 1 1999, and transcriptional map of 30 cDNAs in the 4 Mb candidate region on chromosome 21, as well as sequencing and characterization of a likely candidate., DS-CAM. Analysis of the human and mouse DS CAM clones reveal a highly conserved novel class of cell adhesion...

Cardiovascular Disease

Despite some reduction in recent decades, cardiovascular disease continues to be the most common cause of death, accounting for up to 50 of deaths in developed countries. Incidence and mortality strongly increase with age. In the following, the epidemiology of three major clinical manifestations of cardiovascular disease, coronary heart disease, stroke and heart failure (which to a large extent have common etiologies), will be addressed. Despite a major decline in mortality by more than 50 in the second half of the 20th century, coronary heart disease (CHD) remains the single largest killer, accounting for 20 of all deaths in developed countries such as the United States, where mean age of manifestation of a first heart attack is 65-70 years (American Heart Association, 2005). The major risk factors for CHD, which include hypertension, hyperlipidemia, smoking and diabetes, are well established, and 80-90 of all CHD patients have prior exposure to at least one of these risk factors...

Dietary strategies to prevent the development of heart disease

In 1987, we proposed that inflammation and leucocytes play a role in the onset of acute CHD events. This has recently been confirmed. - It is now accepted that one of the main mechanisms underlying the sudden onset of acute CHD syndromes, including unstable angina, myocardial infarction and SCD, is the erosion or rupture of an atherosclerotic lesion,32'33 which triggers thrombotic complications and considerably enhances the risk of malignant ventricular arrhythmias.34,35 Leucocytes have been also implicated in the occurrence of ventricular arrhythmias in clinical and experimental settings,84 85 and they contribute to myocardial damage during both ischaemia and reperfusion.86 Clinical and pathological studies showed the importance of inflammatory cells and immune mediators in the occurrence of acute CHD events,29,86 and prospective epidemiological studies showed a strong and consistent association between acute CHD and systemic inflammation markers.88,89 A major question is to know why...

Project Title Cardiovascular Disease In The Pima Indians

Summary MedStar (formerly Medlantic) Research Institute proposes to continue its participation in the Strong Heart Study to manage the Arizona field center and the core laboratory. For the field center, this proposal describes methodology for 1) morbidity and mortality surveillance of the original Strong Heart Study cohort (1099 surviving out of 1500 original men and women ages 45-74 years in Phase I) 2) recruitment and examination of 30 families of at least 30 members, each 15 years and older and 3) re-examination of the 900 family members from the Phase Ill pilot study. The Arizona field center comprises three American Indian communities Gila River, Salt River, and Ak Chin. The Arizona center had a 71 recruitment rate in Phase I and 90 + completion rates in Phases II and III. Morbidity and mortality surveillance obtained data on 99 of the participants. The core laboratory will provide accurate, reliable, stable, and comparable phenotypic measures of coronary heart disease risk...

Introduction oxidative stress and cardiovascular disease

This chapter will focus on the potential roles of fat-soluble nutrients and fat-soluble antioxidants in preventing cardiovascular disease (CVD). Two fat-soluble vitamins will be discussed in detail, i.e. vitamin E and vitamin D. Vitamin E (tocopherols and tocotrienols) is generally considered an antioxidant nutrient, although it may have important functions unrelated to its antioxidant functions (as discussed below). Antioxidant nutrients function by preventing damage to biological systems caused by reactive oxygen species (ROS) and or reactive nitrogen oxide species (RNOS). Vitamin D (calciferols) is not a true vitamin since it is not required in our diet, can be produced in skin tissue, and is generally not present in plants. Vitamin D is, perhaps, best described as a steroid hormone precursor. Although vitamin D may function as a membrane antioxidant under in vitro conditions (Wiseman, 1993), its primary biological role is to maintain plasma calcium and phosphorus homeostasis. The...

The impact of cardiovascular disease

Owing to the enormous worldwide impact of cardiovascular disease it must be emphasized that even very modest reductions in risk factors, brought about by the appropriate design and use of functional foods, can have very important health related and economic significance. Statistics from the American Heart Association (see http www.americanheart.org statistics 03cardio.html) indicate the enormous impact of CVD. Over 61 million Americans have one or more types of CVD. CVD causes more mortality each year than the next seven leading causes of death combined and the estimated cost of cardiovascular diseases and stroke in the United States in 2003 was 352 billion. In developed countries, childhood obesity has reached epidemic proportions and this will certainly translate into a dramatic increase in type 2 diabetes which is characterized by elevated levels of triglycerides, LDL-C (low-density lipoprotein-cholesterol) and decreased levels of HDL-C (high-density lipoprotein-cholesterol), i.e....

Antioxidants cardiovascular disease and oxidative modifications of lowdensity lipoprotein

Both lipid-soluble and water-soluble antioxidants present in blood may be important in preventing cardiovascular disease owing to their ability to prevent the oxidation of lipid-protein complexes called lipoproteins. Lipoproteins are extremely important in cardiovascular disease since we know with certainty that high levels of LDL-C cause atherosclerosis, which is the underlying cause of most cardiovascular disease. In contrast, high levels of HDL-C are a negative risk factor for CVD. Atherosclerosis is the gradual build-up of 'plaque' in the arterial wall. LDL-C is the major source of the lipids occurring in these plaques.

Project Title Community Surveillance Of Cardiovascular Diseaserisk F

Summary Data from the most recent survey (1995-97) of the Minnesota Heart Survey (MHS) indicate that previously favorable trends in cardiovascular risk factor levels are attenuating. While cigarette smoking and self-reported dietary fat intake continued to decline, mean body weight rose substantially and rapidly, physical activity decreased, and the previous decline in serum total cholesterol was no longer apparent. These trends may or may not continue in the future. As part of the Minnesota Heart Survey, we propose to conduct another population survey of 4,000 adults, ages 25-84 years in 2000-02, to detect current trends in cardiovascular disease risk factors, including serum lipids, blood pressure, cigarette smoking prevalence, dietary fat intake, obesity, diabetes, physical inactivity, fibrinogen, and serum vitamin E. The proposed survey will build upon four previous, independent cross-sectional surveys conducted in 1980-82, 1985-87, 1990-92, and 1995-97, which collectively...

Project Title Congenital Heart Disease With Lv Noncompaction

Summary Left ventricular non-compaction (LVNC), a form of myocardium disease which presents in infancy as heart failure, is characterized as a hypertrophic and dilated left ventricle with systolic dysfunction, deep endomyocardial recesses and trabeculations, and in some patients, congenital heart disease (CHD). When CHD occurs, it most commonly includes atrial septal defect (ASD), ventricular septal defect (VSD), right heart obstruction, or hypoplastic left heart syndrome. This disorder may be inherited as an autosomal dominant or X-LINKED trait. In the X- linked form, the gene G4.5 which encodes the tafazzin protein, has been found to be mutated in some patients but the mechanism of disease has not been discovered. No gene(s) has been identified for the autosomal dominant form. In the subproject, families with LVNC will be recruited and the genes for the disease will be pursued using a primary candidate gene approach utilizing our final common pathway hypothesis. In this hypothesis,...

Mental Harassment in the Context of Hostility and Cardiovascular Risk

Cynical hostility, measured with various self-report measures (e.g., Cook-Medley Hostility Scale, Ho Scale Cook and Medley, 1954), has been identified as a behavioral risk factor for the development and progression of cardiovascular disease (e.g., Chida and Steptoe, 2009 Smith, 1992), but the ways in which this psychological characteristic contribute to atherogenesis and subsequent coronary events are not well understood. The reactivity hypothesis described in the preceding section has been considered as one plausible explanation for the risk conferred by cynical hostility (e.g., Williams et al, 1985). The idea is that cynically hostile persons may respond with exaggerated cardiovascular physiological responses to provocation. If this is a common phenomenon, then heightened neuroendocrine responses may increase the risk of atherogenesis (see Chapter 13).

HAART lipodystrophy syndrome and cardiovascular risk

The fat redistribution and disturbances in glucose and fat metabolism resemble a clinical situation that is known as the metabolic syndrome in HIV-negative patients. This condition includes symptoms such as central adipositas, insulin resistance and hyperinsulinemia, hyperlipidemia (high LDL, Lp(a) hypertriglyceridemia and low HDL) and hypercoagulopathy. Given the well-established cardiovascular risk resulting from this metabolic syndrome, there is growing concern about a potential therapy-related increased risk of myocardial infarction in HIV patients. These fears are further sustained by reports of arterial hypertension on HAART, a high rate of smoking among HIV patients and increased levels of tissue plasmino-gen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients with lipodystrophy. Although many of the, mainly retrospective, studies dealing with this issue are inconclusive, data from a large international study (D A D study) provide evidence for an increased...

Heart Failure Complicating Acute Myocardial Infarction465

This article addresses issues related to acute myocardial infarction (MI) complicated by heart failure, particularly in elderly patients. Findings have shown that acute MI complicated by congestive heart failure (CHF) is associated with a high mortality, and that women with acute MI are more likely to be older and to develop CHF than men with acute MI. In general, management of CHF complicating acute MI is similar in older and younger patients. Actions discussed include hemodynamic monitoring the administration of oxygen and the use of morphine, diuretics, nitroglycerin, angiotensin-converting

Project Title Coronary Heart Disease Incidence In Relation To Total Homocysteine

Summary We used a prospective case-cohort design to determine whether total homocysteine (tHcy)-related factors are associated with incidence of coronary heart disease (CHD) over an average of 3.3 years of follow-up in a biracial sample of middle-aged men and women. Age-, race-, and field center-adjusted CHD incidence was associated positively (P< 0.05) with tHcy in women but not men, and CHD was associated negatively (P< 0.05) with plasma folate (women only), plasma pyridoxal 5 -phosphate (both sexes), and vitamin supplementation (women only). However, after accounting for other risk factors, only plasma pyridoxal 5 -phosphate was associated with CHD incidence the relative risk for the highest versus lowest quintile of pyridoxal 5 -phosphate was 0.28 (95 CI 0.1 to 0.7). There was no association of CHD with the C677 T mutation of the methylenetetrahydrofolate reductase gene or with three mutations of the cystathionine -synthase gene. Our prospective findings add uncertainty to...

Project Title Coronary Heart Disease Womens Values Beliefs And Cognitive Processes

Summary Coronary heart disease, which includes acute and old myocardial infarction, angina pectoris, and other acute, subacute, and chronic forms of ischemic heart disease, is the single largest killer of American women. In 1999, 262,391 United States women, of all ethnic and racial groups, lost their lives to coronary heart disease. However, Black women have the highest overall death rates from coronary heart disease, followed by White and Hispanic women. Despite these findings and the fact that women are more likely than men to die after a myocardial infarction, women are less likely than men to seek medical attention after the onset of initial symptoms. Explanations for these delays have been linked to low perceptions of susceptibility to heart disease, the lack of association of initial symptoms as significant indicators of an acute cardiac event, low socioeconomic status, and patient race. While not negating the importance of these variables, they do not speak to the values...

CoQIO in heart disease

Variety of cardiovascular disorders, e.g. congestive heart failure, angina pectoris, coronary artery disease, cardiomyopathy, hypertension, mitral value prolapse (Singh et al., 1998). In the apoE gene knockout mice (an excellent model of human atherosclerosis) supplementation with both vitamin E and CoQ10 was found to inhibit atherosclerosis better than with vitamin E or CoQ10 alone (Thomas et al., 2001). It is not known, however, if CoQ10 supplementation in humans can decrease atherosclerosis. Although ubiquinol may inhibit the formation of oxidized and atherogenic forms of LDL, it is likely that the primary mechanism whereby CoQ10 could prevent heart disease is through its ability to improve ATP synthesis in cells with a high ATP demand such as cardiac myocytes. As an antioxidant, ubiquinol could also inhibit the free radical damage to the myocardium that arises during ischemia-reperfusion injury. Heart failure (due to cardiomyopathy and congestive heart failure), as discussed...

Project Title Dietary Etilogies Of Heart Disease And Cancer

Summary (Adapted from Investigator's Abstract) The authors propose to continue the follow-up of 51,529 male health professionals, aged 40 to 75 years in 1986, to address a series of dietary hypotheses related to risk of coronary heart disease, stroke, and peripheral vascular disease. Diet has been assessed in 1986, 1990, and 1994 by a semiquantitative food frequency questionnaire developed and refined by the group over the last 15 years. Detailed studies in a subsample of participants demonstrate that this questionnaire performs well the average correlation between the questionnaire and 14 days of diet recording for 16 nutrients of interest was 0.66. This study population has substantial variation in dietary intake, for example, fat intake varies from 25 to 42 of calories between extreme quintiles. Body fat distribution (assessed by waist and hip circumferences) has been measured twice (1987 and 1996) and weight is updated during every 2-year cycle. The first three follow-up cycles...

Project Title Dietary Etiologies Of Heart Disease And Cancer

Summary (provided by applicant) We propose to continue the biennial follow-up of cardiovascular disease among 51,529 male health professionals, age 40 to 75 years in 1986, to address a series of new dietary hypotheses related to risk of a coronary heart disease and stroke. We project over 4,000 incident MI, fatal CHD, and stroke cases through the end of the follow-up period. Nested within this cohort, over 18,000 participants provided blood samples in 1994 from which we propose to investigate several biological (plasma and genetic) determinants of disease. We will concentrate on several hypotheses related to nutritional and genetic determinants of cardiovascular disease (CVD). With this exceptional resource of repeated assessments of diet and lifestyle characteristics tied to potential genetic markers of disease, we will prospectively evaluate in relation to coronary heart disease 1) n-6 fatty acids across a wide range of n-3 fatty acid intake from fish and vegetable sources, 2) foods...

Vitamin E and other antioxidants in the prevention of cardiovascular disease

On the basis of these data almost all the trials have been based on the assumption that supplementation with vitamin E would represent a useful approach for preventing cardiovascular disease. However, candidates for antioxidant treatment were not accurately defined any patient at risk of cardiovascular events has been indiscriminately enrolled in those trials. We argue that antioxidant status represents an important marker of oxidative stress,7 its determination may be useful for better identifying candidates for antioxidant treatment. In order to substantiate this hypothesis, data inherent to oxidative stress and antioxidant status in patients at risk for cardiovascular disease and in patients included in observational and interventional trials have been reviewed. As antioxidant vitamin E has been the subject of the most important research in this field, our analysis is essentially concentrated on the clinical relevance of this vitamin in patients with cardiovascular disease.

Project Title Effect Of Heart Disease Education On Older Women

Summary This application is aimed at evaluating different health education approaches to improve the health-related quality of life and health care utilization of older women with heart disease. Approximately 1,100 women, who are 60 to 80 years old and have coronary heart disease, will be randomized to one of four treatment conditions 1) usual care control, 2) group-based health education, 3) self-directed education via mail and phone contacts, or 4) a choice of either the self-directed or group program. The programs will be evaluated at 3, 12, and 18 months. The primary outcomes of interest are physical and psychological functioning, frequency and severity of symptoms, and health care utilization. It is hypothesized that both the self-directed and group health education formats will result in better long-term outcomes than usual care, and that the best outcomes will be observed when women are given a choice between either of the formats.

Project Title Endothelial Cell Targeted Gene Therapy Strategies For Coronary Heart Disease

Summary The endothelium appears to play a central homeostatic role in maintaining normal vascular function and structure. Although the association between endothelial dysfunction and vascular disease is well established, its molecular basis and pathogenic significance remains poorly defined. Our central hypothesis poses that normal endothelial function is predicated upon a homeostatic balance between reactive nitrogen species such as nitric oxide (NO) and reactive oxygen species (ROS) such as superoxide anion. Furthermore, we postulate that the NO- ROS balance modulates several critical pathobiological processes involved in atherosclerotic coronary heart disease including endothelial cell-leukocyte adhesion, vascular smooth muscle cell growth and migration, endothelial cell apoptosis, platelet aggregation, and decreased coronary blood flow. This project will test the postulate that the decline in NO bioactivity characteristic of endothelial dysfunction is a critical event in the...

Project Title Etiology And Development Of Congenital Heart Disease

Summary (provided by applicant) One to two percent of human infants are born with congenital heart disease (CHD). The common anatomic forms of CHD include conotruncal defects (CTD) and patent ductus arteriosus (PDA). Studies in human families have shown that CTD and PDA tend to occur in a familial pattern, each type being specific to a particular family. While it is clear that genetic factors are important in the cause of these and other forms of congenital heart disease, the patterns of inheritance in human families tend to be complex, indicating that the combined effects of genes at more than one gene locus are involved. Despite the recent advances in mapping and. characterizing the human genome, progress in identifying the gene defects responsible for congenital heart diseases, including PDA and CTD, has been slow. This is because of the apparent complexity of inheritance, and the lack of large well-characterized families in which it can be assumed that all affected individuals...

Project Title Exercisetraining In Children With Heart Disease

Summary (provided by applicant) The principal investigator will develop expertise in exercise testing and training of children and obtain the experience and skill necessary to initiate independent research projects during the award period. The principal investigator's long-term career goal as an academic pediatric cardiologist is to become a clinical investigator with a research focus in exercise physiology and cardiac rehabilitation. Exercise intolerance is an under-recognized chronic morbidity in children with heart disease. Poor exercise capacity leads to low self-esteem and poor quality of life. Children with single ventricle after the Fontan operation and children after orthotopic heart transplantation (OHT) are among children with the lowest exercise capacity. Whether exercise intolerance in these children is due to cardiopulmonary dysfunction or deconditioning from decreased physical activity remains unclear. The role of skeletal muscle and humoral responses in determining...

Project Title Genetic Analysis Of Inherited Congenital Heart Diseases

Summary (Adapted from the Applicant's Abstract) Congenital heart defects are common human malformations that cause significant morbidity, mortality, in addition to substantial social and economic costs. Birth defect registries indicated congenital heart defects occur in approximately 1 percent of human lie births and 10 percent of stillbirths (1). Over the past 30 years major advances have occurred in the diagnosis and management of heart defects in infants and children. Far less is known about the normal molecular signals or pathways that direct human cardiac morphogenesis, nor how and why these processes sometimes fail. Application of human genetic analysis to the study of inherited congenital heart disease has enormous potential to provide novel insights into these complex human processes. The focus of this application is to define the molecular causes of inherited human congenital heart defects. The investigators have recently identified three loci that cause human cardiac...

Project Title Genetic Basis Of Congenital Heart Disease

Summary Secundum atrial septal defect (ASD) is a common congenital heart defect accounting for 10 of isolated congenital heart disease. Some individuals with ASD have a family history of this defect some familial ASD kindreds also have other congenital heart defects and co-existing atrioventricular (AV) conduction abnormalities. The genetic basis for these observations remains unclear. Preliminary studies on seven kindreds in whom ASD was transmitted as an autosomal dominant trait confirmed these observations and also identified loci on chromosome 5p and 5q through genetic

Project Title Genetic Regulation Of Coronary Heart Disease Susceptibility

Summary Atherosclerotic coronary heart disease (CHD) is the number one public health problem in the United States. CHD has been increasing in prevalence and with the aging of the baby boomers and the increase in major cardiovascular risk factors in the population (smoking, obesity, and physical inactivity) over the last 10 years the problem will be even worse in the 21st century. This is not just a U.S. problem, but is occurring world wide. The WHO has recently predicted that by 2020 heart disease will replace infectious disease world wide as the number one cause of disability expressed as years of healthy life lost to death or disease. CHD is a complex genetic disease with many genes involved and important gene-environment interactions. In this proposal we will use the facilities of the Rockefeller Hospital GCRC to identify and study genes and gene-diet interactions that are important in determining CHD susceptibility.

Project Title Heart Disease And The Emergence Of Modern Epidemiology

Summary (provided by applicant) Epidemiology is currently the science of public health mad file major intellectual system, along with economics, for studying, justifying and developing public health policy. Despite its deep influence on medicine, science, health policy and American culture over the past 40 years, there is presently no systematic history of epidemiology in the United States, particularly for the second half of the 20th century. The objective of this proposal is to write a social and intellectual history of the origins, development, and impact of one of the most important areas of epidemiology during the last century, that of coronary heart disease (CHD). The work will begin early in the 20th century, just before the epidemiological transition, when mortality from heart disease and cancer surpassed deaths from communicable disorders. With this introductory period (1900-1945) as prologue, the book will then focus on the emergence, after World War II, of an epidemiology...

Project Title Intermountain Pediatric Heart Disease Research Center

Summary (provided by applicant) Heart disease is a leading cause of morbidity and mortality in children. A network of research centers with both a sufficient clinical population and team of researchers trained to conduct multi-center trials could provide standardized, blinded, quality research that has the statistical power to change the way children with heart disease are managed. Primary Children s Medical Center, located in Salt Lake City, Utah, is uniquely qualified to participate as a research center within such a network. It serves as the leading referral hospital for children with heart disease in the Intermountain West. The overall goal of the proposed Intermountain Pediatric Heart Disease Research Center is to collaborate in prospective, randomized, multi-institutional trials that provide robust data leading to the advancement of knowledge regarding pediatric heart disease and evidence-based pediatric medicine. The specific aims of the Intermountain Pediatric Heart Disease...

Project Title Ischemic Heart Disease In Womenclinical Center

Summary The primary objective of the Women's Ischemic Syndrome Evaluation Study (WISE)- previously referred to as Evaluation of Ischemic Heart Disease in Women (EIHDW) under RFP NHLBI-HC-94-13, is to perform clinical studies to improve the diagnostic reliability of cardiovascular testing in evaluation of ischemic heart disease in women. Innovative approaches proposed in evaluation of ischemia will include physiologic or functional measurements such as impaired metabolism, perfusion, or endothelial function as well as assessment of epicardial coronary arteries by angiography. Objectives of this study are to develop safe, accurate, and cost effective diagnostic approaches for evaluating women with suspected ischemic heart disease, and to determine the frequency of myocardial ischemia in the absence of significant epicardial coronary stenosis, as well as the frequency of non-ischemic or non-cardiac chest pain. Key to these goals is the improved understanding of chest pain in women....

Project Title MCP1 Induced Gene Expression In Cardiovascular Disease

Summary (provided by applicant) Many recent reports provide strong evidence that MCP- 1 plays a major role in the development of ischemic heart disease (IHD) that is responsible for the majority of the 5 million human heart failure cases in the US, but the underlying mechanism is not known. We postulate that MCP-1-induced gene expression changes in the monocytes and the consequent production of cytokines and other biologically active molecules, as well as possible direct effects of MCP- 1 on the major cell types in the myocardium can lead to the development of IHD. IHD probably develops as a net consequence of the interplay of these events which involve many cell types and many biologically active molecules. Therefore in vitro studies on isolated cells cannot accurately reflect the interactions involved in IND. On the other hand a genomic approach can discover the genes whose altered expression in the heart leads to the development of IHD. Such an approach, although not possible on...

Project Title Molecular Determinants Of Pediatric Heart Disease

Summary The long term objective of this Pediatric SCOR is to determine the molecular bases of defective human cardiac morphogenesis and myocardial function which results in congenital heart disease (CHD) and pediatric cardiomyopathy (CM). The underlying hypothesis is that single gene defects at multiple loci in the human genome cause most pediatric cardiac structural and myopathic diseases. Two corollaries will also be explored, that (i) genetic abnormalities at the same locus have variable expressivity and can result in different phenotypes and (ii) genotype- phenotype correlations exist. A multi-disciplinary approach encompassing 14 investigators, 6 clinical and laboratory projects, and 4 core units at three locations is proposed. Molecular genetic studies of a St. Louis family with dominantly-inherited dilated CM CM or sudden death secondary to mutations in mitochondrial fatty acid oxidation enzymes patients with CHD associated with at the human at the human 8p23 locus encompassing...

Project Title Molecular Mechanisms Of Congenital Heart Disease

Summary The goal of this SCOR project is to further the understanding of the fundamental mechanism of congenital heart disease with the use of the state-of-the-art technology of molecular biology, developmental biology, human genetics, small animal cardiac physiology, and clinical pediatric cardiology. The Harvard SCOR in Pediatric Cardiology would bring together some of the finest basic science research faculty of the Harvard Medical School and its affiliated teaching hospitals. Each participant of this SCOR has a strong track record of making original and fundamental contributions to cardiovascular sciences as it relates to the aim of this RFA. The projects described in this SCOR application are designed to take the maximum advantage of studying the closely related scientific theme using the different model organisms and system to dissect the role of transcription factors and secreted factors in the cardiac morphogenesis and their mutations in human and in experimental animals, as...

Project Title Notch Signaling Pathway Ligands In Cardiovascular Disease

Summary (Adapted from the Applicant's Abstract) Identification of genes causing human cardiac disease provides insight into the molecular pathways involved in heart development. The investigators have recently identified Jagged1 (JAG1) as the disease gene causing Alagille syndrome, a genetic disorder associated with heart, liver, and several other anomalies. JAG1 is a ligand in the Notch signaling pathway, shown in multiple organisms to be involved in cell fate determination. Alagille syndrome is a dominant disorder, with extreme variability in the expression of phenotypic features. Some individuals with JAG1 mutations have only a single clinical feature, rather than the multi- system involvement characteristic of Alagille syndrome, which led the investigators to hypothesize that JAG1 mutations would be identified in patients with isolated heart disease. The preliminary data support this hypothesis, as the investigators have identified three patients with cardiac disease and JAG1...

Project Title Pediatric Heart Disease Clinical Research Network Dcc

Summary (provided by applicant) The Pediatric Heart Disease Clinical Research Network will be a cooperative network of up to six Clinical Centers, a Data Coordinating Center (DCC), and the Division of Heart and Vascular Diseases of the NHLBI. The specific aim of this network is to efficiently conduct multi-center clinical studies (including but not limited to randomized clinical trials), and to evaluate new and existing treatments and management approaches for children with structural congenital heart disease, inflammatory heart disease, heart muscle disease, and arrhythmias. The role of the DCC is to support protocol development for the clinical studies, to provide statistical design expertise, to identify, train, and maintain central laboratories for echocardiography and other cardiac specialties to collect and monitor the data and provide quality assurance in the form of personnel training and site visits to provide overall study coordination including plans for patient recruitment...

Coronary artery disease CHD

In contrast to case reports and autopsy trials analyzing the influence of antiretroviral therapy on myocardial infarction rate, the results of clinical observations appear to be inconsistent. At present, two major clinical trials have been published, and in one of these trials, a retrospective analysis of 36,500 patients, no rise in cardiac or cardiovascular events was detected (Bozzette 2003). Nevertheless, in the second trial, the most extensive prospective study to date, including more than 23,000 patients, a 26 increase in the incidence of myocardial infarction was found with each year of antiretroviral therapy (Friis-Moller 2003). The increased risk of myocardial infar-tion was associated with an increased exposure to protease inhibitors, which is partly explained by dyslipidemia (Friis-Moller N 2007). Today most trials indicate an effect of ART on medical infarction (Obel 2007). Therefore, it could be estimated, that the interruption of ART might reduce the rate of...

Project Title Pediatric Heart Disease Network Chop Membership

Summary (provided by applicant) As a Clinical Center in the new Pediatric Heart Disease Clinical Research Network (PHDCRN), the Children s Hospital of Philadelphia (CHOP) will participate collaboratively with the Network to improve outcomes for children with heart disease, provide an evidential base for therapies currently used or considered, develop new therapies, and disseminate that information to the medical community. To achieve this goal, we will address the following aims Aim 1 Develop an infrastructure and investigational team for to assure full participation in PHDCRN Aim 2 Develop procedures and policies to assure proper implementation of approved PHDCRN protocols Aim 3 Fully participate in the development new protocols and dissemination of information to the scientific community. Two protocols are proposed for the PHDCRN s scientific agenda that emphasize the research strengths of the Cardiology Division, the Cardiac Center and CHOP. The short-term study investigates the...

Valvular heart disease

Valvular heart disease of HIV-infected patients occurs as a bacterial or mycotic endocarditis. In fact, the hypothesis that HIV infection alone makes a subject more susceptible to infective endocarditis could not be validated. However, intravenous drug abusers have a ten- to twelve-fold increased risk for infective endocarditis than non-intravenous drug abusers (Nahass 1990). The most frequent germ is staphylo-coccus aureus, being detected in more than 40 of HIV-infected patients with bacterial endocarditis. Further pathogens include Streptococcus pneumoniae and Hemophilus influenzae (Currie 1995). Mycotic forms of endocarditis, which may also occur in patients who are not intravenous drug abusers, mostly belong to As-pergillus fumigatus, Candida species or Cryptococcus neoformans and are associated with a worse outcome (Martin-Davila 2005).

Hemostasis Factors and Cardiovascular Disease

Numerous large-scale and prospectively designed epidemiologic studies suggest that hemostatic factors, for instance fibrinogen, D-dimer, VWF, and PAI-1, predict cardiovascular disease (CVD) in apparently healthy subjects as well as recurrent events in patients with established CVD (Lowe et al, 2002). These relationships have been shown to be independent of sociodemographic factors, lifestyle, and established cardiovascular risk factors smoking, diabetes, hypertension, and obesity, all of which may affect hemostasis. Altogether, this abundant epidemiologic research challenges the view that hemostasis factors are mere risk markers of CVD and do not actively contribute to atherosclerosis. It is assumed that a procoagulant milieu, as reflected by increased activity of clotting factors, coagulation activation markers, platelets, and the VWF on the one hand and impaired fibrinolysis on the other will gradually contribute to atherosclerosis progression over many decades by promoting fibrin...

Project Title Premenopausal Risk Factors For Coronary Heart Disease In Black White Women

Summary Premenopausal black women have a 2- to 3-fold greater rate of coronary heart disease (CHD) than premenopausal white women. The purpose of this study was to provide greater insight into the reasons for this difference, which are currently unclear. We compared CHD risk factors in 99 black and 100 white, healthy, premenopausal women, aged 18 to 45 years, and of relatively advantaged socioeconomic status. Compared with white women, black women had a higher body mass index (32.0 _ 9.2 vs 29.0 _ 9.4 kg m2, p 0.021), and higher systolic (124 _17 vs 115 _ 14 mm Hg, p< 0.0001) and diastolic (79 _ 14 vs 75 _ 11 mm Hg, p 0.048) blood pressures. The mean plasma lipoprotein(a) concentration was markedly higher in the black women (40.2 _ 31.3 mg dl) than in the white women (19.2 _ 23.7 mg dl, p< 0.0001). The plasma total homocysteine level was also higher in the black women (8.80 _ 3.38 vs 7.81 _ 2.58 umol L, p 0.013). The black women, however, had lower plasma triglyceride levels (0.91...

Osteoporosis and Cardiovascular Disease in the Elderly

Osteoporosis and cardiovascular disease are common disorders that increase with aging. Accumulating evidence indicates that both disorders may share common pathophysiologic mechanisms as well as risk factors. Besides age and sedentary lifestyle, diabetes, hypertension, dyslipidemia, estrogen deficiency, and hyperhomo-cysteinemia are common risk factors for both disorders. Furthermore, therapeutic agents for osteoporosis have antiatherosclerotic properties and agents such as statins that are atheroprotective, and appear to increase bone mass and perhaps protect against fractures.

Project Title Randomized Clinical Trials For Pediatric Heart Disease

Summary (provided by the applicant) The Children s Heart Program of South Carolina is a statewide consortium of pediatric cardiologists, who care for 90 of the 3.7 million residents in the state. This consortium has all the critical elements for a center in the proposed research network adequate patient volume, clinical research infrastructure, a track record of subject enrollment, and a demonstrated dedication to hypothesis driven clinical research. The applicant center, MUSC, is the tertiary referral center for the Children s Heart Program. Current MUSC faculty have participated as PI s in a total of 20 multicenter clinical trials or registries (10 open, 2 under IRB review). The PI of this application has been the lead investigator nationally in 4 of the 20. These protocols range from industry sponsored drug or device trials, to an NIH sponsored drug trial for fetal heart block, to an NIH prospective registry. The faculty also currently runs 11 local clinical research protocols....

Project Title Randomized Therapeutic Trials In Pediatric Heart Disease

Summary (provided by applicant) This grant application proposes two randomized, double-blind, placebo-controlled trials to be performed in the Pediatric Heart Disease Clinical Research Network. Our shorter-term trial will study the efficacy and safety of pulse steroid therapy, when added to conventional therapy with intravenous gamma globulin (IVIG) plus aspirin, in treatment of acute Kawasaki disease. Patients will be randomly assigned to receive either methylprednisolone (IVMP), 30 mg kg, plus conventional therapy (i.e., IVMP plus IVIG) versus placebo plus conventional therapy (IVIG alone). Our first aim is to test the hypothesis that treatment of acute Kawasaki disease with IVMP plus IVIG is more effective than treatment with IVIG alone. Our primary efficacy outcome variables will be BSA-adjusted coronary artery dimensions (z-scores) for the proximal right, left main, and proximal left anterior descending coronary

Genetics of human coronary heart disease

Genome-wide studies for coronary heart disease The heritability of known risk factors that were included in this linkage study (including type 2 diabetes mellitus and hypertension) was high, suggesting that these intermediate phenotypes are genetically determined to a moderately high extent. However, whereas age, gender, diabetes and hypertension contributed significantly to the myocardial infarction phenotype, high cholesterol levels did not. Since many of the individuals in the study were on lipid-lowering therapy, this suggests that hypercholesterolemia now appears to be a less significant risk factor for myocardial infarction than diabetes and hypertension. The genome scan in Icelandic subjects localized a susceptibility gene for both myocardial infarction and stroke to chromosome 13 and identified the likely gene as 5-lipoxygenase activating protein (FLAP) (Helgadottir et al., 2004). The FLAP gene product converts 5-lipoxygenase to leukotriene B4, a powerful inflammatory...

Project Title Reducing Heart Disease Risk With Getthefatout

Summary (provided by investigator) Despite enormous public health efforts, heart disease remains the number one killer, partly due to the prevalence of high dietary fat intake and sedentary lifestyles. At the same time and for many of the same reasons, obesity is becoming increasingly prevalent, bringing with it increased risk of heart disease, hypercholesterolemia, diabetes, hypertension, and some forms of cancer. In an effort to address the dietary behaviors that promote both heart disease and obesity, Health Management Consultants of Virginia proposes to develop Get-the-Fat-Out, an Internet data based behavior modification program targeted for at-risk adults at varying stages of readiness for changing dietary fat intake and physical activity level. The ultimate goal of Get-the-Fat-Out is to facilitate life-long habits of maintaining a healthy weight, an active lifestyle, and a low-fat diet. Specific aims for Phase I are 1) Develop initial and on going intervention-integrated...

Project Title Reducing Prehospital Delay Acute Myocardial Infarction

Summary Background - Individuals who experience the symptoms of acute myocardial infarction (AMI) often delay hours or even days before seeking medical treatment. Median prehospital delay times (i.e., between the onset of cardiac symptoms and arrival at the hospital) have been documented to be 2.0 to 6.0 hours in numerous studies conducted over the past three decades. Such delays result in significant morbidity and mortality. Purpose - We propose a randomized experimental trial to determine whether a one-to-one education and counseling intervention delivered specifically to patients with documented ischemic heart disease will 1) reduce prehospital delay, 2) increase 911 use, and 3) increase aspirin use in those patients who experience AMI symptoms. Other aims to be tested relate to hypothesized changes in resource utilization knowledge, attitudes, and beliefs about heart disease and AMI symptoms and perceived control and anxiety. The effect of various sociodemographic characteristics...

Autoimmune Prone Mice as a Model of Chronic Inflammation and Heart Disease

Inflammation is a key component in the development of heart disease (Ross, 1999). The inflammatory process is propagated by immune cells like the T cell, which migrate to the site of inflammation. This is significant because the T cell plays a critical role in determining both the type and extent of immune response via the production of cytokines. Specifically, T cells have been shown to drive the inflammation found in atherosclerotic lesions (Benagiano et al., 2003). The inflammation in arterial walls is propagated by both the expression of adhesion molecules like ICAM-1 and VCAM-1, which recruit immune cells to the site of inflammation, and the production of cytokines by both nonimmune and immune cells. The autoimmune prone MRL-lpr has been used as an experimental system to examine chronic inflammation and heart disease (Qiao et al., 1993) primarily because many of the adhesion molecules and cytokines thought to be important in human atherosclerosis are up-regulated in this animal...

Project Title Scor In Ischemic Heart Disease In Blacks

Summary The Ischemic Heart Disease in Blacks Specialized Center of Research at Boston University School of Medicine will provide a multi-disciplinary approach to the study of vascular function and dysfunction relevant to the pathogenesis of cardiovascular disease in blacks. We postulate that the principal cardiovascular disorders common among blacks-hypertension, left ventricular hypertrophy, and myocardial ischemia without epicardial coronary disease-result from a specific vascular diathesis that is a consequence of increased oxidant stress. This unifying theme for our proposal represents a direct outgrowth of the first five years of SCOR support during which we demonstrated that one component of the vascular diathesis of blacks is nitric oxide insufficiency, which we find to be a consequence of its increased oxidative inactivation. The fundamental mechanism(s) underlying this increased oxidant stress is a major focus of this program, and we proposed to address the issue using a...

Project Title Sleep Heart Health Study

Summary The Sleep Heart Health Study (SHHS) was started in 1994 as a multicenter cohort study of the cardiovascular consequences of sleep-disordered breathing (SDB). The study's principal aims are to assess SDB as a risk factor for adverse cardiovascular outcomes, including incident coronary heart disease events, stroke, and hypertension, and accelerated increase in blood pressure with age. The SHHS protocol added an assessment of SDB to ongoing cohort studies of cardiovascular and other diseases, including the Framingham Offspring and Omni cohorts, the Hagerstown and Minneapolis St. Paul sites of the Atherosclerosis Risk in Communities (ARIC) Study, the Hagerstown, Sacramento, and Pittsburgh sites of the Cardiovascular Health Study (CHS), the Strong Heart Study (SHS) sites South Dakota, Oklahoma, and Arizona, and cohort studies of respiratory disease in Tucson and of hypertension in New York. During its first four years (1994-1998), the SHHS was successfully started with full and...

Project Title Social Change Heart Disease And Depression

Summary INVESTIGATOR'S The research is part of a larger goal to understand the role of culture on the experience of heart disease, depression, and their co-morbidity. The research begins with a cultural investigation of post-socialism in eastern Germany, but will culminate in an understanding of illness as a meaningful experience in a context of rapid social change. Research suggests that heart disease (and heart disease co-morbid with depression) is sensitive to biologic and psychosocial variables, but few studies have investigated the role of culture in heart disease, or its co-morbid state. This work builds on research into culture and hypertension, and culture and depression, to fill a gap in our understanding of the cultural processes at work in the expression of heart disease, but adds a new dimension by exploring co-morbidity. The research will take place in eastern Germany, where individuals are at increased risk to both conditions since 1989. Research aims include 1) a...

Metabolic Syndrome and Cardiovascular Risk

The disease most studied in relation to obesity is diabetes. The precursor to type 2 diabetes and to cardiovascular disease in many patients is the metabolic syndrome. By definition, this is said to be present if three or more of the following five conditions are met In a study of over 12,000 Japanese subjects (Hasegawa et al., 2005), factor analysis was used to examine the relationship between cardiovascular risk factors. In this extensive study, the major influence of BMI was in younger subjects. Similarly, in another Japanese study involving nearly 160,000 subjects (Wakabayashi et al., 2004), the influence of BMI on blood pressure was much weaker in the elderly. The concept of the metabolic syndrome has been useful in screening populations who are at risk from diabetes and cardiovascular disease. It is important to realize, however, that susceptibility to the individual risk factors and disease states that relate to the syndrome are caused by multiple factors, not all of which...

Project Title Sodm For Management Of Ischemic Heart Disease

Summary (provided by applicant) Recent studies in models of cardiac ischemia reperfusion injury have shown that a significant reduction in tissue damage from infarction can be achieved using MetaPhor's proprietary superoxide dismutase mimetics (SODm). In preliminary studies we found that M40403 a selective and potent SODm preserved cardiac function following ischemia reperfusion injury. Based on the data that free radical generation, especially superoxide, may play a critical role in mediating tissue damage and death in heart following an ischemic event, such as a heart attack, we propose to develop a SODm mimetic of the M40403 class as a novel parenteral agent for administration after cardiac infarction or ischemia. M40403 will not be developed for this indication for reasons that are discussed in the proposal. Instead M40401, an SODm with higher catalytic activity, similar stability and improved toxicity to M40403 will be pursued. Given the enormous need for improving the outcome of...

Project Title Specialized Center Of Research In Ischemic Heart Disease

Summary This proposal describes a Specialized Center for Research (SCOR) in Ischemic Heart Disease that tests the hypothesis that the genetics, expression and function of cardiovascular estrogen receptors (ER) and estrogen-regulated target genes mediate protection against ischemic diseases and their sequelae, including vascular dysfunction, post- myocardial infarction remodeling, and arrhythmias. The program is based on widely noted gender differences in ischemic disease, beneficial effects of estrogen on cardiovascular diseases in women, and recent data demonstrating 1) the presence of functional ER in cardiovascular diseases in women and men 2) important ER target genes in cardiovascular tissues and 3) an important role for ER and the genes they regulate in vascular and myocardial physiology. The hypothesis is investigated through genetic, molecular, cellular, animal and human studies in five highly integrated and cooperative projects that expand on existing strengths at New England...

Ace Inhibition In Heart Failure And Ischaemic Heart Disease

Many clinical trials demonstrate the therapeutic benefit of ACE inhibition in heart failure and ischaemic heart disease. It is of note, however, that the effects of ACE inhibitors are dose related. Large clinical trials, by necessity, use only one dose of any drug. The results of such trials are just as much a measure of the effect of the dose as they are a measure of the effect of the drug. Use of a less than optimal dose may fail to reveal a drug's true therapeutic potential. This is of particular concern in a head-to-head comparison of two active drugs, where the result may be more due to choice of dose than to choice of drug. Clinicians should strive to achieve drug doses that have proven to be of benefit in clinical trials. At present, a large proportion of patients receiving ACE inhibitor therapy are receiving less than optimal doses (Lenzen et al 2005). Measurement of plasma Ang peptide levels is not feasible for the monitoring of ACE inhibitor therapy, but measurement of...

Project Title Teaching Nutrition To Prevent Cardiovascular Diseases

Summary As Director of the Division of Nutrition at Harvard Medical School (HMS), Dr. Allan Walker will direct the development and implementation of a curriculum to teach nutrition principles and clinical practice skills for the prevention of cardiovascular diseases, hypertension, diabetes and obesity to medical students, house staff and practicing physicians. The nutrition theme will enrich and extend the current curriculum and core clinical clerkships and create a new elective clinical rotation. The specific aims are to 1) develop a four-year, cardiovascular disease specific nutrition curriculum for HMS students by a) developing didactic lectures b) developing clinical cases based on patients in Dr. Welty's secondary prevention program, Heart and Sole, and women's and lipid clinics for case-based teaching c) developing a teaching module on women, diet and heart disease in collaboration with the NIH funded Harvard Center of Excellence in Women's Health. All lectures, cases and...

Project Title The Sleep Heart Health Study

Summary The Sleep Heart Health Study (SHHS) was started in 1994 as a multicenter cohort study of the cardiovascular consequences of sleep-disordered breathing (SDB). The study's principal aims are to assess SDB as a risk factor for adverse cardiovascular outcomes, including incident coronary heart disease events, stroke, and hypertension, and accelerated increase in blood pressure with age. The SHHS protocol added an assessment of SDB to ongoing cohort studies of cardiovascular and other diseases, including the Framingham Offspring and Omni cohorts, the Hagerstown and Minneapolis St. Paul sites of the Atherosclerosis Risk in Communities (AMC) Study, the Hagerstown, Sacramento, and Pittsburgh sites of the Cardiovascular Health Study (CHS), the Strong Heart Study (SHS) sites in South Dakota, Oklahoma, and Arizona, and cohort studies of respiratory disease in Tucson and of hypertension in New York. During its first four years (1994-1998), the SHHS was successfully started with full and...

Project Title The Sleep Heart Health Study Reading Center Application

Summary The Sleep Heart Health Study (SHHS) was started in 1994 as a multicenter cohort study of the cardiovascular consequences of sleep-disordered breathing (SDB). The study's principal aims are to assess SDB as a risk factor for adverse cardiovascular outcomes, including incident coronary heart disease events, stroke, and hypertension, and accelerated increase in blood pressure with age. The SHHS protocol added an assessment of SDB to ongoing cohort studies of cardiovascular and other diseases. During its first four years (1994-1998), the SHHS was successfully started with full and high quality polysomnography (PSG) data obtained in the home from 6,440 participants. Initial cross-sectional findings show that SDB is common and associated with hypertension and self-reported cardiovascular disease (CVD). The clinical centers are now requesting another five years of support to collect additional endpoints needed for testing primary SHHS hypotheses. Additionally in Years 7-9, PSG will...

Coronary Heart Disease 21 Risk Factors

The leading cause of death worldwide is CHD (WHO, 2008). Although atherosclerosis, the preclinical antecedent of CHD, begins in childhood, the clinical manifestations of CHD occur in adulthood and include angina pectoris, MI, heart failure, and sudden death. Major cardiovascular risk factors are those that independently influence the development of atherosclerosis and CHD. More than a half century ago the Framingham Heart Study identified cigarette smoking, elevated serum cholesterol, hypertension, and advancing age as major risk factors (Dawber et al, 1951). Since then, conventional wisdom has come to accept that four modifiable traditional cardiovascular risk factors (i.e., smoking, hypertension, hypercholesterolemia, type 2 diabetes mellitus) account for only 50 of the risk for CHD (Braunwald, 1997 Hennekens, 1998). However, some investigators have contended that the 50 figure is a myth and that traditional risk factors account for far more than half the prevalence of CHD (Canto...

Isoflavones and coronary heart disease

The increase in coronary heart disease (CHD) incidence associated with decreased ovarian function at the menopause (McGrath et al., 1998 Bittner, The oestrogenicity of isoflavones was first documented over 50 years ago, when isoflavones present in the diet of sheep were found to be responsible for the permanent infertility induced in these animals. Subsequent epidemiological evidence in humans suggested that high soy consumption, the main dietary source of isoflavones, was cardioprotective, in part attributed to the ability of the isoflavones in soy to act as oestrogen mimics. Demonstration of the ability of soy products to bring about a beneficial change in the blood lipoprotein profile led the US Food and Drug Administration (FDA, 1999) to approve a claim that '25g of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease'. It is currently uncertain whether soy isoflavones contribute to the cholesterol-lowering effects that...

Project Title Subclinical Heart Disease In Insulindependent Diabetes

Summary Approximately 10 percent of premature coronary artery disease (CAD) morbidity and mortality in the general population is due to insulin dependent diabetes mellitus (IDDM). By age 55, 35 percent of IDDM patents die of CAD, in contrast to only 8 percent of nondiabetic men and 4 percent of women. In the U.S., IDDM affects at least 750,000 persons and this number is growing rapidly as the effect of increasing incidence and improved survival. Tight blood glucose control ran slow the development of microvascular complications but a protective effect on heart disease has not been convincingly demonstrated. This observational population-based study will evaluate cross- sectionally a population-based group of 800 IDDM patients aged 20-49 years and 600 of their non-diabetic spouse partner controls using the electron-beam computed tomography (EBCT). We will compare the patients and controls in terms of the amount and anatomical distribution of coronary artery calcium (CAC), a marker of...

Project Title Cholesterol Lowering By Nurses To Control Heart Disease

Summary The purpose of this study is to evaluate the effectiveness of a nurse-managed, case-management system of individualized lifestyle modification and pharmacologic intervention to manage lipid disorders in adults who have undergone coronary artery bypass graft surgery (CABG). Clinical trials have provided strong scientific evidence that lowering serum cholesterol will reduce morbidity and mortality from coronary heart disease (CHD) in patients with established CHD.1 Despite the clear benefits of cholesterol-lowering treatment, many patients with clinical evidence of atherosclerosis are not being treated effectively .2-4 Changes in the delivery of health care, including care for and after coronary events, mandate that we consider more effective and economical strategies for the management of lipid disorders in those with CHD so that the benefits of lipid lowering can be achieved outside of clinical drug trials. The primary aims of this study are to 1. compare the effectiveness of...

Focal Ischemic Stroke Models

Focal ischemic stroke models, whether in larger mammals such as cats, dogs, or nonhuman primates, or in small mammals such as rodents, usually involve occlusion of one MCA (Lipton 1999). Focal ischemia is differentiated from global ischemia in two ways. First, even at the core of the lesion, the blood flow is almost always higher than during global ischemia so that longer insults are required to cause damage. Second, there is a significant gradation of ischemia from the core of the lesion to its outermost boundary, and hence there are different metabolic conditions within the affected site. Because of its duration and heterogeneity, the insult is much more complex than global ischemia, but it is an invaluable model for stroke and is thus widely studied. There are two models of focal ischemic stroke transient focal ischemia and permanent focal ischemia. In transient focal ischemia models, vessels are blocked for up to 3 h, followed by prolonged reperfusion, whereas in permanent focal...

Psychosocial Behavioral Interventions with Acute Coronary Syndrome Patients

Linden et al (1996) conducted a meta-analysis on 3,180 CHD patients in 23 randomized controlled trials (RCTs) and found that patients who did not receive psychosocial-behavioral treatment showed greater mortality (0R 1.70 95 confidence interval CI , 1.09-2.64) and MI recurrence (0R 1.84 CI, 1.12-2.99) than those who did. Similarly, Clark et al (2005) conducted a meta-analysis on 21,295 CHD patients in 63 RCTs and reported an 0R 0.85 CI, 0.770.94 for all-cause mortality and 0R 0.83 CI, 0.74-0.94 for recurrent MI. More recently in a meta-analysis conducted on 9,856 CHD patients in 43 RCTs, Linden et al (2007) found that trials initiating treatment at least 2 months after a cardiovascular event revealed greater mortality savings than those beginning treatment sooner (0R 0.28 CI, 0.11-0.70 vs 0R 0.87, CI, 0.86-1.15, respectively). Moreover the mortality benefits applied only to men (0R 0.73 CI, 0.57-1.00) but not to women (0R 1.01, CI, 0.87-1.72). In general then, meta-analyses have...

Project Title Genetic Architecture Of Heart Disease In Rural Brazil

Summary (provided by applicant) This project has the ultimate goal of elucidating the genetic architecture of Chagas' disease in a population residing in rural Brazil. A leading cause of heart disease throughout Latin America, it affects between 16 and 18 million individuals. In Brazil alone, approximately 10 percent of the population is seropositive for T. cruzi, the parasitic cause of the disease, with sub-populations experiencing seropositivity rates as high as 65 percent. Given the large pool of primary hosts for this zoonotic disease, complete eradication of Chagas' disease through control of the arthropod vector is unlikely. Research with humans and animal models indicates that there is variation in susceptibility to infection, and disease outcome, and that this variation may be due to genetic factors. Thus, this form of heart disease represents a complex phenotype with potential genetic determinants to both susceptibility to infection and differential disease pathogenesis. The...

Treatment Of Isolated

Isolated HIT refers to HIT diagnosed on the basis of thrombocytopenia alone, rather than because of HIT-associated thrombosis. Often, the initial reason for administering heparin includes routine postoperative prophylaxis or a medical indication such as acute stroke or myocardial infarction. Until the early 2000s, the standard approach upon suspecting HIT in such patients was discontinuation of heparin, sometimes with substitution of oral anticoagulants. Prophylaxis after hip replacement surgery Prophylaxis after knee replacement surgery Prophylaxis after hip fracture surgery Extended prophylaxis after hip replacement surgery Extended prophylaxis after hip fracture surgery Prophylaxis after general (abdominal) surgery Prophylaxis for unstable angina and non-Q wave myocardial infarction (given together with aspirin) Acute deep-vein thrombosis, with or without pulmonary embolism,d,e together with warfarin Prophylaxis in medical patients at risk for deep-vein thrombosis or pulmonary...

Alzheimers Disease And Atherosclerosis

A second age-related pathology in which chronically-activated T cells may play a role is atherosclerosis. Immune involvement in cardiovascular disease (CVD) is suggested by both epidemiological data and experimental animal models. T cells are present in atherosclerotic lesions (Libby et al., 1995), and interaction of CD40 on T cells with vascular endothelial cells, smooth muscle cells, and macrophages has been documented (Mach et al., 1997). Importantly, several types of infections have been hypothesized to increase the risk of CVD by causing systemic inflammation, or by triggering autoimmunity, for example, by cross-reactivity of heat shock proteins (hsp) with bacterial antigens (Mayr et al., 1999). Indeed, clinically healthy volunteers with sonographically documented carotid artery atherosclerosis have significantly increased antibody titers to hsp 65 compared to controls with no lesions, and in follow-up studies, those with highest titers showed highest mortality. The blocking of...

Clinical Development Of Hematopoietic Growth Factors

The clinical development of recombinant forms of HGF were directed by an extensive understanding of the biologic effects of these factors. The human gene encoding EPO was cloned in 1983 (22), and clinical development of epoetin alfa began soon after. Initial studies were focused on patients with an endogenous EPO deficiency, such as patients with severe chronic renal failure receiving dialysis. The effects of epoetin alfa were apparent in the first dose levels with an increase in hemoglobin concentration and hematocrit. A reduction in the requirement for red blood cell transfusions was ultimately proved in the pivotal phase 3 trial. Further studies focused on defining a safe rate of rise in hemoglobin and an appropriate target however, a conservative target rather than normalization of hematocrit was initially approved in the dialysis setting. In patients with underlying heart disease, the safety and benefits of correction to a normal hematocrit are still under investigation almost 20...

Failure Laws In Survival Studies

In this formula the first, age-independent term (Makeham parameter, A) designates the constant, ''nonaging'' component of the failure rate (presumably due to external causes of death, such as accidents and acute infections), while the second, age-dependent term (the Gompertz function, Reax) designates the ''aging'' component, presumably due to deaths from age-related degenerative diseases like cancer and heart disease.

Functional foods defined

Functional foods that are marketed with claims to reduce heart disease focus primarily on the risk factors of blood cholesterol, homocysteine and hypertension. This can be done by a reduced content of food components that are known to increase risk, such as saturated fat or sodium. More recently products have been designed that are enriched in components that are thought to reduce risk. The most common 'protective' ingredients include fibres, soya, omega-3 fatty acids, phytostanols and phytosterols, and (antioxidant) vitamins. These components have cholesterol or homocysteine-lowering abilities in metabolic studies. The added ingredients may be food components that are often deficient in Western diets, such as calcium and folate. Their recommended intake could, however, be achieved by 'normal' foods. The added ingredients may also be nutrients or phytochemicals that are normally

Exercise Treadmill Testing

Exercise treadmill testing is the gold standard for the assessment of cardiorespiratory fitness or aerobic capacity. The results of exercise treadmill testing can be used to establish baseline cardiorespiratory fitness to facilitate the creation of a tailored exercise prescription. Exercise treadmill testing can also be utilized following exercise training as a post-treatment measure of change. In clinical cardiology, treadmill tests are routinely used to evaluate the presence and prognosis of ischemic heart disease.

Health benefits of whole foods over isolated components

There are many claims made in the media and promotional literature about the qualities and benefits of specific (or groups of) compounds found in fruits and vegetables. We are told that wrinkles, absentmindedness, cancer and clogged arteries (among many other disorders) can be prevented, or alleviated, by consuming these compounds in the form of isolates or concentrated extracts. In such claims the words 'tested', 'effective', 'safe', 'essential' and 'proven' are freely used. In the world of nutritional science, however, the picture is not so clear. The following two quotes provide an example of this apparent contradiction. The first relates to a study of antioxidant vitamins and risk factors for cardiovascular disease, 'These results back-up the findings of previous studies and point to a positive role for antioxidant supplementation among those suffering from coronary artery disease'.25 The second statement is again related to antioxidants and chronic As with the carotenoids,...

The use of functional foods to meet dietary guidelines

Replacement of saturated or trans fat in the diet by carbohydrates or other types of fat reduces the risk of coronary heart disease.11'12 Margarines were rich sources of trans fat until about a decade ago, but food manufacturers have markedly reduced the trans fat content since reports on adverse health effects. Margarines and yogurts have been enriched with plant stanols or sterols, which lower low-density lipoprotein (LDL) cholesterol by 10 per cent and could thus make an important contribution to prevention of coronary heart disease.40 Many well-controlled trials have documented the efficacy of sterols and stanols for lowering LDL, and no major adverse effects have been noted. However, long-term safety and clinical efficacy have not been evaluated in large-scale clinical trials of the size and duration customary for new drugs. The Health Council of The Netherlands therefore discourages the use of plant sterols by consumers who would not benefit from a cholesterol-lowering effect,...

Arterial Thrombosis

Lower limb artery thrombosis was the first recognized complication of HIT (Weismann and Tobin, 1958 Roberts et al., 1964 Rhodes et al., 1973, 1977). Arterial thrombosis most commonly involves the distal aorta (e.g., saddle embolism) or the large arteries of the lower limbs, leading to acute limb ischemia with absent pulses. Sometimes, platelet-rich thromboemboli from the left heart or proximal aorta explain acute lower limb arterial ischemia (Vignon et al., 1996). Other arterial thrombotic complications that are relatively common in HIT include acute thrombotic stroke and myocardial infarction. The relative frequency of arterial thrombosis in HIT by location, namely, lower limb artery occlusion > > stroke syndrome > myocardial infarction (Benhamou et al., 1985 Kappa et al., 1987 Warkentin and Kelton, 1996 Nand et al., 1997), is reversed from that observed in the non-HIT population (myocardial infarction > stroke syndrome > > lower limb artery occlusion).

Harvard Alumni Activity Survey

The Harvard Alumni Activity Survey is a brief, seven-item, expedient measure of physical activity (Paffenbarger et al, 1978b). It was constructed for use in the Harvard Alumni Health Study, which investigated the role of physical activity as a risk factor for myocardial infarction. This self-report questionnaire asks respondents to recall the types and duration of physical activities engaged in during the past week. The survey assesses the number of flights of stairs climbed, number of city blocks walked, and what sports were played (hours per week). A physical activity index representing total energy expenditure (expressed in kilocalories per week) is estimated based on values for each activity that is derived from the literature. One year test-retest reliability is reported to be 0.73 and energy expenditure as measured using this scale has been shown to be inversely related to the risk of first heart attack (LaPorte etal, 1983).

Minnesota Leisure Time Physical Activity Questionnaire

The Minnesota Leisure Time Physical Activity Questionnaire (LTPA Taylor et al, 1978) is designed to quantify energy expenditure during leisure time physical activities. It was originally created to assess the relationship between physical activity intensity and coronary heart disease risk. Respondents indicate which activities they have engaged in over the past 12 months and then a trained interviewer collects detailed information regarding activity type, duration, and frequency for each reported activity. Intensity codes in metabolic equivalents are available for 62 leisure activities. The product of each intensity code and duration of activity in minutes (MET*min) is summed for all activities to produce a total Activity Metabolic Index (AMI), expressed in MET*min day. Light (sum of all activities with intensity codes < 4.0 METs), moderate (sum of all activities with intensity codes between 4.5 and 5.5 METs), and heavy (sum of all activities with intensity codes > 6.0 METs) AMIs...

The Combined Health Information Database

The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and heart disease, you will need to use the advanced search options. First, go to http chid.nih.gov index.html. From there, select the Detailed Search option (or go directly to that page with the following hyperlink The trick in extracting studies is found in the drop boxes at the bottom of the search page where You may refine your search by. Select the dates and language you prefer, and the format option Journal Article. At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display whole records. We recommend that you type heart disease (or synonyms) into the For these words box. Consider using the option anywhere in record to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this...

Clinical Studies 61 Bronchodilation

Banner et al. summarized studies where the effects of ephedrine and ephedra were compared to placebo in controlled studies in humans. None of the controlled trials disclosed any evidence of cardiovascular toxicity when ephedrine was given in doses as high as 1 mg kg, even when it was administered to severe asthmatics with known cardiac arrhythmias (57). The trial reported by Banner et al. studied the respiratory and circulatory effects of orally administered ephedrine sulfate, 25 mg, aminophylline, 400 mg, terbutaline sulfate, 5 mg, and placebo in 20 patients with ventricular arrhythmia by a double-blind crossover method. The study was comprised of 20 patients, with an average age of 60 years and a preexisting history of both asthma and heart disease (as evidence by the presence of frequent premature ventricular contractions). The bronchodilator effect of terbutaline was similar to that of aminophylline over 4 hours but superior to ephedrine at hour 4. Both terbutaline and ephedrine...

And Outflow Tract And Atrial And Ventricular Septation

Despite its clinical importance, to date almost nothing is known about the molecular pathways that determine cell lineages in the cardiac neural crest or that regulate outflow tract septation (14). However, it is known that if the cardiac neural crest is removed before it begins to migrate, the conotruncal septa completely fails to develop, and blood leaves both the ventricles through what is termed a persistent truncus arteriosus, a rare congenital heart anomaly in humans. Failure of outflow tract septation may also be responsible for other forms of congenital heart disease, including transposition of the great vessels, high ventricular septal defects, and tetralogy of Fallot (8,16,18).

Increasing consumption what is being done

In several programmes, emphasis is placed on the education and involvement of children, because many of the processes linked to the development of chronic disease begin in childhood. Evidence from the Bogalusa Heart Study, tracking early risk of heart disease among American children, suggests that eating habits in childhood have a potential lifelong effect on cholesterol levels and on adult coronary heart disease.32 A study of British schoolchildren found that children who ate fruit more than once per day had better lung function compared with those who did not. The difference was evident even after controlling for possible confounding factors such as social class and passive smoking.33 A further study in Italy found that even low intakes of fruit can reduce wheezing and asthma with effects being most noticeable in children with a history of respiratory problems.34 Continued attention to increasing fruit and vegetable consumption in children is viewed as a practical and important way...

Overview of Dietary Assessment in Behavioral Medicine

Nutritional status is one of the most important predictors of health risk. Research consistently demonstrates that diets rich in fruit, vegetables, whole grains, and lean meats from poultry and fish are inversely associated with risk of age-related chronic diseases such as cardiovascular disease, cancer, and diabetes (Kushi et al, 2006 Lampe, 1999 Neuhouser, 2004 Pool-Zobel et al, 1997 Prentice et al, 2004 World Cancer Research Fund AICR, 2007). Conversely, diets high in refined grains and added sugars, but low in diverse plant foods, increase risk for obesity and obesity-related disorders including cardiovascular disease, cancer, and diabetes (Boynton et al, 2007 Kristal et al, 2000 National Research Council Committee on Diet and Health, 1989 Patterson et al, 2004). Despite the strong and consistent diet-disease associations and recommendations to the public to make healthy food choices and limit or avoid added fats, sodium, and empty calorie-type foods, consumers still, for the most...

Neurological Disorders

Many strokes attributed to ephedrine have actually been caused by the ingestion of ephedrine enantiomers, pseudoephedrine (82-85), phenylpropanolamine (86-93), and even methylephedrine (77). Two cases of ischemic stroke have been reported (94,95), but in neither case was their any toxicological testing to confirm the use of ephedrine. A decade-old report described the autopsy findings in three individuals with intracerebral hemorrhage and positive toxicology testing for ephedrine however, one had hypertensive cerbrovasular disease and the other had a demonstrable ruptured aneurysm (96). Intracerebral hemorrhage has also been described in suicide and attempted suicide victims who took overdoses of pseudoephedrine (97,98). There is also a report describing a patient who developed described arteritis following the intravenous administration of ephedrine during a surgical procedure (99). On the other hand, a large study to assess risk factors for stroke in young people (age 20-49) over a...

Project Title Ace Inhibition In Single Ventriclepulmon Hypertension

Summary (provided by applicant) The overall goal of this application is to examine treatment modalities which may improve the clinical care of two groups of patients with congenital heart disease infants born with a single ventricle supplying blood flow to the lungs and body and children with pulmonary hypertension associated with congenital heart disease. The primary hypothesis in infants with single ventricle is that chronic angiotensin converting enzyme (ACE) inhibition favorably modifies the ventricular remodeling response to volume overload and improves ventricular function over the first year of life. Serial changes in ventricular geometry will be assessed using magnetic resonance imaging and compared with measurements of systolic and diastolic function, including the pressure volume relation and the Tei index, and clinical outcome measures including post-operative course and changes in the Ross heart failure classification. The beneficial effect of ACE inhibition is expected to...

Reaching beyond Researchers

Other resources explain particular age-related diseases. The Centers for Disease Control Cardiovascular Health site contains information for lay people such as fact sheets on topics that include cholesterol, heart attacks, and high blood pressure. Of particular interest to researchers are the interactive maps that supply heart attack and stroke mortality rates for the state, gender, and racial ethnic group of choice. The site includes a list of Morbidity and Mortality Reports that relate to cardiovascular disease as well as other statistical and public-health information. NIH's Osteoporosis and Related Bone Diseases-National Resource Center offers background articles on topics of interest to researchers as well as lay people these include ''Vitamin A and Bone Health,'' ''Phytoestrogens and Bone Health,'' and ''Bone Mass Measurement What the Numbers Mean.''

Differing types of claim nutritional and health claims

Claims that suggest that foods or food components have an impact on health - in improving good health or a condition related to a disease - have been called health claims.5,10 An important subgroup of claims are disease-risk reduction claims. They state that a food or its component may help to reduce the risk of a disease. Examples of such claims include 'Adequate intake of calcium may help to reduce the risk of osteoporosis', 'Adequate intake of folate by women may reduce the risk of having children with neural tube defect', 'Food low in fat and cholesterol can help to reduce the risk of coronary heart disease'.

Project Title Aging Estrogen Hsps And Myocardial Ischemia

Summary (Adapted from the Investigator's abstract) The heat shock proteins (HSPs) are an important family of endogenous, protective proteins found in all tissues. In the heart, HSP72, the inducible HSP70, is increased by ischemia and is cardioprotective. Overexpression of other HSPs also protects against cardiac injury. Aging results in a decreased heat shock response in male rats the effect on females in unknown. Women have less cardiovascular disease than men, but postmenopausal women have an increased incidence of heart disease. Although some of estrogen's protective effects can be explained by changes in lipoprotein profiles, other, unknown factors are involved. Studies in the Principal Investigator's laboratory have shown that estrogen increases levels of HSPs in male rat cardiac myocytes. We hypothesize that, as estrogen increases HSP expression and estrogen protects against CV disease, the decrease in estrogen with aging is associated with a decrease in HSP expression, and...

General Health Benefits

Studies examining the benefits of sexual activity on physical health have suggested sexual activity improves physical and psychological health in a number of domains. Sexual activity (1) Increases longevity Men with increased orgasmic frequency (i.e., had sex at least two times per week) had a 50 lower risk of mortality at a 10-year follow-up (Davey Smith et al, 1997) (2) Lowers the risk of chronic disease (e.g., heart disease and cancer) Among men, frequency of sex was associated with a lower risk of fatal coronary heart disease (Ebrahim et al, 2002). Furthermore, a national survey of US men found high ejaculation frequency (i.e., > 21 ejaculations per month) was associated with decreased risk of total prostate cancer (Leitzmann et al,

Contribution To Heart Development

An understanding of the mechanisms of human heart development provides clues to the etiology of congenital heart disease. Nevertheless, to date, the genetic regulatory mechanisms of these developmental processes are just starting to be characterized. A molecular review of heart development is outside the scope of this chapter, but several interesting molecular heart reviews have been published (14,52,53). A better understanding of the embryological origins of the heart combined with the characterization of the genes that control heart development (54) may lead to many new clinical applications to treat congenital and adult heart disease.

Project Title Alcohol Induced Immunomodulationretroviral Cardiopath

Summary Cardiomyopathy and left ventricular dysfunction are prevalent in people with AIDS or chronic alcohol use. However almost nothing is known of the combined effects of retroviral infection plus alcohol on heart disease. Our murine retrovirus infection mimics much of the cytokine dysregulation found during HIV infection, prompting inflammatory damage for cardiac toxicity. We found that alcohol consumption exacerbated many immune, oxidative, and nutritional defects due to murine retrovirus infection. We found that alcohol + retrovirus exposure was particularly toxic, increasing Th2 and reducing Th1 cytokines, dramatically lowering cardiac vitamin E, increasing oxidation of cardiac lipids and synergistically promoting severe heart damage due to Coxsackie B3 infection. Our overall hypothesis is that the combination of ethanol + retroviral infection induces immune dysfunction and oxidation for increased cardiovascular disease. These effects should promote growth and pathogenesis of...

Intramyocardial Pump Model General Concept

Although coronary blood flow is phasic and the direction of flow varies with both vessel type and location in the myocardium, it is not necessary to take this fact into account at all levels of analysis of coronary flow. In general, one will use mean values of coronary flow and pressure to describe in global terms the distribution of blood flow across the ventricular wall, control of coronary blood flow, and hemodynamic consequences of an obstruction caused by coronary artery disease. However, one has to be aware of the fact that most of the elements are nonlinear and time dependent in their physical behavior, meaning that neglecting the time-varying nature of flow and pressure can result in erroneous conclusions.

Project Title Anxiety Vagal Control Of The Heart In Coronary Disease

Summary Coronary heart disease continues to be the leading cause of death in the United States, despite risk factor reduction and technological advances in treatment options. Prospective studies implicate chronic anxiety as an independent risk factor for fatal coronary heart disease. In particular, anxiety increases the risk of sudden cardiac death substantially. The primary objective of the proposed research is to examine the role of reduced vagal control of heart rate in the increased risk of cardiac mortality associated with anxiety in a population with established coronary artery disease (CAD). A second objective is to determine whether the effects of anxiety are independent of the effects of depression. Nine hundred and fifty CAD patients will be recruited for this study from patients hospitalized for elective cardiac catheterization. Anxiety will be measured by the Hospital Anxiety Scale, the Spielberger Trait Anxiety Inventory, and the Crown-Crisp Phobic Anxiety Scale. Symptoms...

Project Title Azithromycin And Coronary Events

Summary This study is to determine whether the antibotic, azithromycin, decreases the risk of having a heart attack or other complication related to coronary artery disease in people with heart disease. Azithromycin is an antibiotic that is used to treat infections with a bacteria called Chlamydia pneumoniae. Some studies suggest that Chlamydia pneumoniae infection may be a risk factor for heart attacks and other complications related to coronary artery disease. Chlamydia pneumoniae is spread from person-to-person by sneezing and coughing (unlike a related bacteria, Chlamydia trachomatis, it is not a sexually transmitted disease). Studies show that people who have been infected with Chlamydia pneumoniae in the past have a higher chance of having a heart attack. Other studies show that Chlamydia pnreumoniae is present in the plaque, or material blocking the heart vessel, in many people with heart disease.

Racial Mortality Crossover Phenomenon

There is a notable exception to lower life expectancy for African Americans compared to whites 75 to 80 years of age. At this point, a convergence occurs whereby African Americans have more expected years remaining than whites (Wing, Manton, Stallard, Harnes, & Tyroler, 1985 Manton, 1980). We call this the racial mortality crossover phenomenon. There are also racial crossover patterns in death from heart disease and certain types of cancer (National Center for Health Statistics, 1980).

Project Title Betareceptors And Cardiovascular Pharmacogenomics

The focus of the candidate s research program is to determine the impact of beta-adrenergic receptor (betaAR) polymorphisms on drug response and cardiovascular disease. This broad research objective will be carried out through several studies. The first set of studies is focused in hypertension (HTN), which aim to test the hypotheses that the betaAR genes a) are associated with HTN b) are disease modifying in HTN, with a particular focus on the nocturnal blood pressure decline causing individuals to be either nocturnal dippers or nondippers and c) are important determinants of the antihypertensive response to beta-blockers. The latter aim will be tested in a small population, with focus on the blood pressure, and also through a pharmacogenetic substudy of the INVEST trial, a 22,000 patient outcomes trial in patients with hypertension and documented ischemic heart disease. The second group of studies focus on beta-blocker pharmacogenetics in heart failure. Beta-blockers...

Frequency of HIT in Medical Patients Treated with Porcine Mucosal UFH

Table 2 also lists the frequency of HIT observed in several prospective studies that have evaluated medical patients receiving intravenous, therapeutic-dose porcine UFH, usually for venous thromboembolism (VTE), myocardial infarction and acute coronary syndromes (MI ACS), or hemodialysis (HD). Excluding studies of HD, an overall frequency of HIT of slightly less than 1 is suggested. This is a relatively low number, particularly when one considers that, paradoxically, the frequency appears to be much higher in postoperative surgical patients who received lower (prophylactic) doses of porcine heparin (discussed subsequently).

Project Title Bone Marrow Angioblasts For Myocardial Vasculogenesis

Summary Congestive heart failure remains a major public health problem, and is frequently the result of left ventricular remodeling after myocardial infarction. We have recently shown that human adult bone marrow contains endothelial progenitors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to induce vasculogenesis after experimental myocardial infarction. This results in decreased apoptosis of hypertrophied myocytes, long- term salvage and survival of viable myocardium, reduction in collagen deposition, and sustained improvement in cardiac function. Thus, the use of cytokine-mobilized autologous human bone marrow-derived angioblasts offers the potential to significantly reduce morbidity and mortality associated with left ventricular remodeling. However, a number of studies have provided evidence that the ability of bone marrow-derived stem cells to respond to environmental demands such as injury, disease or other physiologic...

Adoption of the Regimen

Least two clinical encounters (Shah et al, 2009). In the same practice, 85 of new diabetes prescriptions were filled (Shah et al, 2008). For patients recently discharged from hospital after a myocardial infarction, 77 of discharge prescriptions were filled within 7 days (Jackevicius et al, 2006). In this situation, closed health-care systems may detect failure to fill through close monitoring of pharmacy fills. But for the open systems where patients may utilize any number of pharmacies, failure to adopt the regimen is unlikely to be detected until the next healthcare visit, perhaps as long as 6-12 months after the prescription is written. It is unknown how many persons take the first step in behavioral interventions. Many factors may influence the patient's adoption of treatment including those noted above combined with a reluctance to question or challenge the provider. Other factors may include barriers to obtaining the prescription such as cost, accessibility, and availability.

Project Title Calcium Regulation In The Diabetic Heart

Summary Heart disease is the leading cause of death in diabetic patients, and considerable evidence is now available to support the existence of a specific diabetic cardiomyopathy that is independent of coronary artery disease and hypertension. Functional and biochemical data acquired from multicellular cardiac preparations of diabetic animals support the view that cellular mechanisms controlling cytosolic Ca2+ on a beat-to-beat basis are abnormal and contribute to impaired relaxation. The goal of this project is to characterize diabetes-induced changes in the expression and function of Ca2+ regulating proteins in isolated cardiac myocytes, and to determine the role of hyperglycemia in the pathogenesis and pathophysiology of diabetic cardiomyopathy. To test the hypothesis that abnormal Ca2+ handling occurs at the single cell level, biophysical assessment of excitation-contraction coupling will be carried out in ventricular myocytes isolated from diabetic rats. Voltage clamp techniques...