Reverse Heart Disease Book

The Big Heart Disease Lie

The Big Heart Disease Lie is a book written by doctors who are members of the International Truth In Medicine Council they are also the authors of The Big Diabetes Lie. In this book you will be getting over 500 pages of scientifically proven, doctor verified information that you will not find anywhere else, not even bookstores.If you have high blood pressure or cholesterol, fatigue, shortness of breath, irregular heartbeat, swollen feet or ankles, chest pain, fainting, diabetes, asthma or allergies, pain, fatigue, inflammation, any troubling health issue, or simply want to discover the most powerful health and anti-aging program, then you really need to read this book. The book is a step by step guide that contains techniques scientifically verified and proven by doctors to reverse the symptoms of heart disease, and normalize blood pressure and cholesterol levels. These techniques have been used successfully by tens of thousands of people all over the world, and allowed them to take health into their own hands, ending the need for drugs, hospitals, doctors' visits, expensive supplements or grueling workouts. More here...

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Cardiovascular Disease

L-Carnitine supplementation in doses ranging from 2 g to 4 g day has been investigated in a number of controlled studies involving subjects with angina, heart failure, cardiogenic shock, cardiomyopathy and post myocardial infarction. Overall, positive results have been obtained and reduced mortality reported for some populations. Post myocardial infarction A dose of 4 g day l-carnitine over 12 months improved quality of life and increased life expectancy in patients who had suffered a Ml, according to a controlled study (Davini et al 1992). This included an improvement in heart rate, systolic arterial pressure, a decrease in anginal attacks, and improve

Preventing Cardiovascular Disease

The cardioprotective properties of quercetin, demonstrated in animal and in vitro studies, provide a theoretical basis for the use of quercetin in the prevention of cardiovascular disease however, current human data is less encouraging. A double-blind, placebo-controlled study investigating the effects of a quercetin-containing supplement on plasma quercetin status, risk factors for heart disease and serum platelet fatty acid levels was conducted on 27 healthy men and women with cholesterol levels of 4.0-7.2 mmol L (Conquer et al 1998). The subjects consumed a quercetin-containing supplement (1 g quercetin day) or rice flour placebo for 28 days. Quercetin intakes were approximately 50-fold greater than dietary intakes previously associated with lower coronary heart disease mortality in epidemiologic studies. Plasma quercetin concentrations were approximately 23-fold greater in subjects consuming the quercetin capsules than in the placebo group. Quercetin supplementation did not alter...

Coronary heart 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). However, the total incidence of myocardial infarction was small in both trials. Therefore, current treatment regimens for HIV infection might have no considerable impact on myocardial infarction rate and the concerns of cardiovascular complications have to be balanced against the marked benefits of antiretroviral treatment. Nevertheless, prevention of...

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.

Cardiovascular Disease Prevention

Selenium may decrease cardiovascular disease mortality however, epidemiological studies have produced mixed results. morbidity and mortality (Salonen et al 1982). A more recent study of just over 3000 middle-aged and elderly men also established an association between low serum selenium levels and a significantly increased risk of ischaemic heart disease (Suadicani et al 1992). Alternatively, no association was identified between serum selenium levels and coronary deaths or myocardial infarctions in a study of 1110 men however, a significant association with stroke mortality was detected (Virtamo et al 1985). No significant primary preventative effect was seen for selenium supplementation (200 g day) and incidence of cardiovascular disease, myocardial infarction, stroke or all cardiovascular disease mortality in the Nutritional Prevention of Cancer study (Stranges et al 2006). Lack of association was confirmed when analyses were further stratified by tertiles of baseline plasma...

Myocardial Infarction

There is some reason to believe that activated platelet activity may play a role in plaque formation if the reaction is overresponsive and can also contribute to some instances of myocardial infarction. Thus, TX production by platelets would be balanced by PGI2 production. Sticky platelets could have a negative effect on the development of myocardial infarction over the long term, and some claims have been made that chronic aspirin users could have a lower incidence of myocardial infarction, the explanation being that TX

Prospective Study of Obesity and Risk of Coronary Heart Disease Among Diabetic Women

Summary This article reports on a study undertaken to examine the relationship of obesity, measured as BMI, and weight change to incidence of coronary heart disease (CHD) among women with diabetes. The authors followed 5,897 women with type 2 diabetes in the Nurses' Health Study for up to 20 years. Women were aged 40 to 74 years and had no history of cardiovascular disease or cancer at the beginning of the follow up period. During follow up, the authors document 418 incident cases of CHD (236 of nonfatal myocardial infarction and 182 of fatal CHD). After adjustment for age, smoking, and other coronary risk factors, current BMI (body mass index) was strongly associated with increased risk of CHD among women with diabetes. Increasing BMI values from age 18 years to 1976, before diagnosis of diabetes, were also positively associated with risk of CHD. Weight gain before the diagnosis of diabetes was related to increased risk of CHD. In contrast, weight change after diagnosis of diabetes...

Cardiovascular Disease in the Medico Legal Era An Introduction

The United States is a litigious society, far more so than other regions of the world with sophisticated healthcare systems and economies comparable to ours, such as Canada, Western Europe and Great Britain, and Japan. A major focus of this litigation deals with medical malpractice, with patients or survivors suing healthcare providers for either a real or claimed injury. Cardiovascular disease represents a disproportionate number of these cases, along with failure or delay in the diagnosis of cancer, or complications following surgery. The defense of these cardiovascular law suits often requires knowledge of complex medicine, and a correlation with cardiac pathology and pathophysiology. Similarly, the plaintiff must be aware of mechanisms of cardiovascular disease and the actual pathology in order to make an effective argument to ajury. Other types of litigation such as personal injury (e.g. automobile accident), or product liability (e.g. adverse drug affects, or claims that cars or...

Heart Disease A Cardiologists POV

Summary This article, written by a cardiologist with a family history of diabetes, discusses the personal events that led to his interest in the cardiovascular effects of diabetes. The article begins with the author's recollections of his family's attitude about his grandfather's diabetes. This is followed by an account of his father's problems with high blood glucose and its effects on his heart. In addition, the author recounts his own experience with the effects of high blood glucose, its effects on his body, and his realization of the connection between diabetes and heart problems.

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...

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...

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...

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 (Seaberg 2005), a high rate of smoking among HIV patients and increased levels of tissue plasminogen 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 of...

Kawasaki Syndrome and Acquired Heart Disease

Summary This journal article provides health professionals with information on the etiology, clinical presentation, diagnosis, and management of Kawasaki syndrome (KS). This multisystem inflammatory disorder of unknown cause most commonly affects young children. Although the cause of KS is unknown, an underlying genetic predisposition is suspected based on familial cases and twin studies. When KS is not recognized and managed early, children with the condition may develop coronary artery aneurysms or associated cardiac abnormalities. KS is the leading cause of acquired heart disease in children. All of the signs and symptoms of KS are common and nonspecific, which complicates the diagnosis. Although the diagnosis often involves uncertainty, the following clinical features help distinguish KS from illnesses that mimic

NCEPDefined Metabolic Syndrome Diabetes and Prevalence of Coronary Heart Disease Among Nhanes Iii Participants Age 50

Summary Although the individual components of the metabolic syndrome are clearly associated with increased risk for coronary heart disease (CHD), the authors of this study wanted to quantify the increased prevalence of CHD among people with metabolic syndrome. The authors used the Third National Health and Nutrition Examination Survey (NHANES III) to categorize adults over 50 years of age by presence of metabolic syndrome, with or without diabetes. Metabolic syndrome is very common, with approximately 44 percent of the united States population over 50 years of age meeting the criteria. in contrast, diabetes without metabolic syndrome is uncommon (13 percent of those with diabetes). Older Americans over 50 years of age without metabolic syndrome, regardless of diabetes status, had the lowest CHD prevalence. The prevalence of CHD markedly increased with the presence of metabolic syndrome. Among people with diabetes, the prevalence of metabolic syndrome was very high, and those with...

Helicobacter Pylori Infection as a Risk Factor for Gastrointestinal Symptoms in Patients Using Aspirin to Prevent

Summary Aspirin use in the secondary prevention of ischemic heart disease may provoke gastrointestinal (GI) discomfort. This article reports on a study undertaken to register GI symptoms and complications in patients with cardiovascular disease using aspirin and to relate these symptoms to infection with H. pylori. Blood samples were obtained from 398 consecutive patients in the Coronary Care Unit at a hospital in the Netherlands samples were analyzed for serum antibody levels to H. pylori infection. Questionnaires were sent 2 weeks after discharge to assess GI symptoms. Questionnaires were returned by 314 patients (79 percent). A total of 183 out of 314 patients (46 percent) reported GI symptoms. Of the 238 patients using 80 to 100 milligrams of aspirin daily, 145 (61 percent) recorded GI symptoms. Besides aspirin, the use of calcium antagonists was correlated with GI symptoms. Of the 128 patients using calcium antagonists, 84 (66 percent) reported GI symptoms. The prevalence of GI...

Reduced Mortality In Coronary Heart Disease

The most likely mechanism by which ALA may prevent coronary heart disease (CHD) mortality is by reducing cardiac arrhythmia. In Western populations, almost 50 of all deaths from cardiovascular disease can be attributed to sudden cardiac death and the majority of sudden deaths are directly caused by acute ventricular arrhythmia (Brouwer et al 2004). A review in 2001 (Lanzmann-Petithory) and a meta-analysis of three studies in 2004 (Brouwer et al) both found in favour of a protective effect from increased ALA consumption against fatal CHD (RR 0.24). The dose associated with this trend was small only 1-3 g day ALA higher than controls (Brouwer et al 2004). A study published in 2005, which derived data from the Nurses' Health Study (Albert et al), found that women consuming ALA in the highest two quintiles had a 38-40 lower risk of sudden cardiac death than women in the lowest quintile however, the protective effect did not extend to other fatal forms of CHD or non-fatal myocardial...

Cardiovascular Disease Protection Independent Of Homocysteine Status

In the absence of a causal relationship between homocysteine and cardiovascular disease, what remains most promising for folate are studies illustrating its protective 2007 Elsevier Australia Several studies show the cardiovascular protective effects of folic acid, including the predictive value of low folate status on stroke risk (Verhaar et al 2002, Bazzano et al 2002). Few interventional studies have been conducted and on the whole results have been disappointing, which may be because the trials are commonly looking at folate in secondary prevention rather than primary. One such study was an open label trial of 500 g day folate over 2 years in 593 patients, which failed to reduce cardiovascular events (Liem et al 2003).

Ischemic Heart Disease

The underlying pathogenesis of ischemic heart disease is the gradual development of an atherosclerotic plaque. Patients develop clinical symptoms either through diminution of blood flow through a stenotic vessel or with acute ischemia due to thrombus formation on a ruptured plaque. The realization that acute thrombus formation underlies most acute presentations of ischemic heart disease has revolutionized cardiology. Four of five clinical trials using aspirin have established that it is effective in primary prevention of myocardial infarction. The side effects of gastrointestinal bleeding and, more importantly, intracranial hemorrhage, occur more frequently with aspirin use. In the lowest risk patients the use of aspirin is not warranted. Patients with even modest risk factors should be on aspirin therapy unless there is a contraindication. Most men and women over 50 years of age are aspirin candidates. Patients under 50 years of age with evidence of atherosclerotic vascular disease...

Valvular Heart Disease

Valvular heart disease of HIV-infected patients occurs as a bacterial or mycotic endocarditis. The most frequent germ is staphylococcus 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 intra

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...

Prevention Of Morbidity And Mortality Of Cardiovascular Disease

For over 25 years, fish and fish oils have been linked to cardiovascular health. This association was first recognised when significantly lower death rates from acute myocardial infarction (Ml) were found among Greenland's Inuit population, despite only moderate differences between the Inuits' blood cholesterol levels and those of other populations (Holub 2002). A high dietary omega-3 fatty acid intake in the form of marine mammals (seal, whale) and various fish were thought responsible for the protective effect (Bang et al 1980). In 1989, results from the first large, randomised, clinical trial investigating the effects of fatty fish consumption on survival and risk of secondary Ml confirmed a link to cardiovascular health (Burr et al 1989). The DART (Diet and Reinfarction study) found a modest intake of 2-3 portions weekly of fatty fish reduced mortality in men who had previously experienced a Ml and produced a relative reduction in total mortality of 29 during the 2-year follow-up,...

Keep Your Heart Healthy

Cardiovascular disease (CVD) is the leading cause of death among New Yorkers, with 27,000 CVD-related deaths reported each year (New York City Department of Health and Mental Hygiene, 2004b). One quarter of New York City adults have been diagnosed with high blood pressure, and a similar number have been diagnosed with high cholesterol, with many more remaining undiagnosed. One-sixth of New York City adults are obese, and three-fourths of New Yorkers do not get at least 30 minutes of physical activity four or more days per week. More than 500,000 adult New Yorkers (9 ) have been diagnosed with diabetes, a 2 2-fold increase in the past decade. Another 250,000 New Yorkers may have diabetes and not know it, and close to a million more with pre-diabetes are likely to eventually develop diabetes. Blood pressure and cholesterol can be controlled with diet, exercise and medications. Control of blood pressure with medications significantly reduces the incidence of stroke, heart attack and...

Heart Disease and Diabetes

Summary This brief fact sheet reminds readers of the connection between heart disease and diabetes. The fact sheet notes that many conditions that increase one's changes of getting heart disease are more common in people with diabetes. These conditions include cholesterol problems, high blood pressure (hypertension), overweight, and blood clotting problems. Heart attacks, known in the medical community as myocardial infarctions, are one of the most common heart conditions. For most people, a heart condition leads to symptoms such as chest pain or pressure, jaw pain, arm pain, shortness of breath, sweating, and pounding heartbeat. However, many people with diabetes and heart disease do not notice any symptoms at all. This is called silent ischemia. Silent ischemia is very dangerous because it may prevent patients with heart problems from seeking medical care and getting early treatment. The fact sheet lists common risk factors for heart disease, and encourages readers with those risk...

Prevention Of Cardiovascular Disease

The association between vitamin C and cardiovascular disease prevention is still unclear, although several themes are emerging as evidence accumulates. In general, laboratory, epidemiological and observational follow-up studies suggest that vitamin C is associated with reduced incidence of cardiovascular disease although not all studies are positive (Houston 2005). Studies have looked at blood levels, dietary intake and supplemental vitamin C and in some studies, vitamin C is co-administered with other nutrients (often vitamin E) making it difficult to assess the contribution of vitamin C alone (Carr & Frei 1999, Khaw et al 2001, Knekt et al 2004, Kushi et al 1996, Lopes et al 1998, MRC BHF 2002, Ness et al 1996, Nyyssonen et al 1997, Osganian et al 2003). It appears that if a protective effect is observed with supplementation, it is most likely with doses above RDI, long-term use and in populations with a substantial proportion of persons who have low or deficient intakes of...

Genetics of human coronary heart disease

Major Risk Factors For 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...

Chest Pain and Myocardial Infarction

Cardiac Risk factors Hypertension, hyperlipidemia, diabetes, smoking, and a strong family history (coronary artery disease in early or mid-adulthood in a first-degree relative). PMH History of diabetes, claudication, stroke. Exercise tolerance history of peptic ulcer disease. Prior history of myocardial infarction, coronary bypass grafting or angioplasty.

Heart Disease

Elevated homocysteine levels Elevated fasting plasma concentrations of homocysteine have a high prevalence in subjects with cardiovascular disease and have also been associated with an increased risk of atherothrombosis in most, but not all, prospective studies (van Guldener & Stehouwer 2001). Clinical studies have found that supplementation with vitamin B6 significantly reduces plasma homocysteine concentrations (Lakshmi & Ramalakshmi 1998). In practice, pyridoxine is typically recommended together with folic acid and vitamin B12. Improving outcomes after heart transplantation Cardiac transplantation represents a potentially life-saving procedure for patients with end-stage cardiac disease. Short-term survival is improving because of improved immunosuppression, but long-term survival remains limited by an aggressive form of atherosclerosis known as transplant coronary artery disease (Miner et al 2001 ).

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...

Acknowledgements

The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on heart disease. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the...

Forward

In March 2001, the National Institutes of Health issued the following warning The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with heart disease is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about heart disease, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and...

Table of Contents

Studies on Heart Federally Funded Research on Heart Chapter 2. Nutrition and Heart Finding Nutrition Studies on Heart Chapter 3. Alternative Medicine and Heart Chapter 4. Dissertations on Heart Dissertations on Heart Chapter 5. Clinical Trials and Heart Recent Trials on Heart Chapter 6. Patents on Heart Patents on Heart Patent Applications on Heart Chapter 7. Books on Heart Chapters on Heart Chapter 8. Multimedia on Heart Bibliography Multimedia on Heart Chapter 9. Periodicals and News on Heart Newsletters on Heart Academic Periodicals covering Heart The Genome Project and Heart Associations and Heart

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...

Cardiac evaluation studies

Baseline EKG usually normal in 25-50 of patients with coronary artery disease but no prior myocardial infarction. EKG evidence of ischemia often becomes apparent only during chest pain. 3. Exercise stress testing gives estimate of functional capacity along with the ability to detect EKG changes and hemodynamic response. Highly predictive when ST-segment changes are characteristic of ischemia. A normal test does not exclude coronary artery disease but suggests that severe disease is not likely.

Issues In Diagnosis And Treatment

The Hachinski Ischemic Score (HIS Hachinski, Lassen, & Marshall, 1974) as modified by Rosen, Terry, Fuld, Katzman, and Peck (1980) is an autopsy-validated index for the diagnosis of vascular dementia. This scale includes a history of sudden onset, stepwise progression, stroke risk factors, stroke or transient ischemic attack, asymmetry or focal signs on examination, and so on. Again, patients may have a combined diagnosis of AD and vascular dementia. Finally, other potentially confounding diagnoses are the frontotemporal dementias linked to neurofibrillary tangles (the tauopathies). Phosphorylated tau is the major component of neurofibrillary tangles, and some familial frontotemporal dementias are linked to mutations and polymorphisms in the tau gene on chromosome 17. Frontotempo-ral dementia may be distinguishable from AD by consensus criteria (Neary, Snowden, Gustafson, Passant, Stuss, et al., 1998) such as early loss of personal and social awareness, hyperorality, stereotyped...

Evaluation Of The Vasculature

AORTA AND OTHER MAJOR ARTERIES In general, the thoracic and abdominal portions of the aorta are opened posteriorly, between the origins of the right and left intercostal and lumbar arteries. In cases of congenital heart disease, the thoracic aorta is left attached to the heart. If an acute aortic dissection is suspected, the heart and the entire aorta should be removed intact transsection of the ascending aorta may distort or destroy the intimal tear. For the evaluation of renovascular disease, the kidneys and renal arteries are best kept together with the abdominal aorta.

Overview Of Racialethic Minority Health

Despite the fact that whites are the older group among the American population, blacks exhibit a 32 higher age-adjusted all-cause mortality rate, when compared to whites. American Indians or Alaska Natives, latinos and Asians or Pacific Islanders exhibit lower age-adjusted all-cause mortality rates by at least 28 than whites (Freid, et al., 2003). A similar scenario can be observed for selected causes of deaths such as heart disease, cancer and diabetes (Table 1). Blacks exhibit 28 and 26 higher age-adjusted mortality rates for disease of the heart and cancer,

Clinical manifestations

Cardiovascular increased circulating blood volume, increased cardiac output, increased oxygen consumption, systemic hypertension, coronary artery disease, congestive heart failure, and pulmonary hypertension. Cardiac output increases by 0.1 L min kg of adipose tissue.

Neurophysiological Factors

As discussed in Chapter 3, organic brain disorders can have a pronounced effect on behavior and abilities. This is particularly evident in Alzheimer's disease, a disorder that afflicts approximately 20 of individuals in the 75- to 84-year age range and about 47 of those over 85 (Evans et al., 1989). An even greater percentage of older Americans suffer from hypertension, another disorder that is associated with reduced intellectual functioning (Hertzog, Schaie, & Gribbin, 1978 Sands & Meredith, 1992) and which can lead to cardiovascular disease and stroke. By interfering with the oxygen flow to the brain, a major stroke can affect not only intellectual abilities but also speaking, walking, and other skills. The brain's blood supply can also be temporarily reduced by emphysema, acute infection, poor nutrition, injuries, and surgery. The loss of neuronal tissue, changes in metabolic rate, and a decline in blood circulation also have depressing effects on cognitive functioning....

Microscopic Description

The heart revealed extensive subendocardial myocardial infarction (SEMI) with granulation tissue, organizing myocytolysis, and focal immature connective tissue. All findings consistent with a 10-14 day old healing infarction. In addition, in the same region of subendocardial myocardial infarct, there was an acute myocardial infarction with extension toward the epicardial surface. This acute transmural infarction extension had predominantly occurred within the past 12-24 hours. Moreover, there were few foci with active neutrophilic inflammation, and thus consistent with 24-48 hours duration. This pattern of SEMI with acute transmural extension was apparent in multiple sections of the left ventricle. The pathologic findings consistently dated the subendocardial infarction between 10-14 days, and the acute transmural extension to 1-2 days. In addition to the acute and organizing necrosis, there was evidence of myocellular hypertrophy and multiple foci of interstitial and replacement...

Clinical Features and Pathology

Friedreich ataxia (FA) is the most common of the early-onset hereditary ataxias in Indo-European and North African populations. The disease was first described in 1863 by Nickolaus Friedreich, Professor of Medicine at Heidelberg. Although Friedreich's papers described the essential clinical and pathological features of the disease as degenerative atrophy of the posterior columns of the spinal cord leading to progressive ataxia, sensory loss and muscle weakness, often associated with scoliosis, foot deformity and heart disease, subsequent descriptions of atypical cases and of clinically similar diseases clouded classification for many years. Diagnostic criteria were established in the late 1970s, after a renewed interest in the disease prompted several rigorous clinical studies (Geoffroy et al. 1976 Harding 1981). The following clinical features were considered essential to establish the diagnosis (1) autosomal recessive inheritance, (2) onset before 25 years of age, (3) progressive...

Arrhythmogenesis and Changes in Impulse Propagation

Experimentally, fractionated electrograms have been be recorded from the surface of a myocardial infarction in a dog 8 weeks following the acute event. These fractionated electrograms are the fingerprint of delayed conduction of the type that underlies reentry. Interestingly, action potentials recorded from myocytes within these zones are normal (Gardner et al., 1985 Ursell et al., 1985). When looked at under the microscope, the muscle fibers were widely separated and disoriented by connective tissues. The slow, fragmented activation that gave rise to the fractionated electrograms, therefore, occurred in the presence of normal action potentials, indicating that the fragmentation and fractionation were not due to changes in the active generator properties of the tissue, but rather to disruption in the integrative electrotonic interaction between cells caused by fibrosis that physically disconnected the cells.

Laboratory data and other tests

The patient was admitted to rule out myocardial infarction and to work up her syncopal episodes. The day after admission she complained of chest pain, which subsided with sublingual nitroglycerin. Her ECG at the time showed ST elevations in many leads. Soon thereafter, she began gasping and became pulseless. Resuscitation efforts were unsuccessful

Stimulation of Thrombocytosis and Thrombosis

In none of the closely followed animal or human studies with TPO has there been any evidence for increased thrombotic events, but three potentially prothrombotic attributes of TPO deserve attention. These molecules are extremely potent growth factors and can markedly increase the platelet count in a short period. The deposition of platelets in an extravascular shunt in baboons is directly related to the platelet count after PEG-rHuMGDF administration (50,51). Since the extravascular shunt mimics an ulcerated atheroma in humans, these results show that except for its ability to increase the platelet count, PEG-rHuMGDF does not synergize with or exacerbate platelet deposition. Nonetheless, increasing the platelet count in individuals with active arterial thrombotic disease may exacerbate the cardiovascular disease.

HDACs In Smooth Muscle

MEF2 is required for vascular development (78) and mediates endothelial cell survival (79). In addition, genetic studies in humans implicate MEF2 in protection from coronary artery disease and myocardial infarction (80). Studies to determine the interplay between HDAC7 and MEF2 in the control of these developmental and pathophysi-ological processes are forthcoming.

Sites and Mechanisms of Drug Action

State-dependent duality of drug action has demonstrated itself dramatically in the clinical situation. That antiarrhythmics could exacerbate rather than control arrhythmias has long been known. Proarrhythmia was initially thought to be relatively uncommon, but awareness increased. More recently, the class IC drugs flecai-nide and encainide proved to have an unacceptably high association with fatal ventricular arrhythmias in the CAST CAST Investigators, 1989 Cardiac Arrhythmia Suppression Trial II (CAST-II) Investigators, 1992 . Patients in CAST had coronary artery disease and existing ventricular arrhythmias that had been well suppressed by these drugs. These patients were randomized either to placebo or to treatment with the drug that had suppressed the ventricular arrhythmia. An interesting observation was that the deaths were distributed equally throughout the period of drug treatment. As the task force of the working group on Arrhythmias of the European Society of Cardiology wrote...

Ischemia vs Nonischemia

It would certainly appear that the presentation is most consistent with ischemic heart disease. The acute onset of chest pain with radiation to the left arm is strongly suggestive of this conclusion. She did not have diaphoresis, nausea, or vomiting, all signs and symptoms of ischemic heart disease, but very variable in their presence. Furthermore, as described below, the ischemia may not have been persistent. Although one must consider other causes of chest pain, it is difficult to explain the nature of these complaints with chest wall disease (e.g. costochondritis, or myositis), muscle strain, pericarditis, pleuritis, or parenchymal pulmonary disease (including pulmonary embolism). When one adds the electrocardiographic findings to the clinical complaints, it strengthens the association even further with ischemia. The fact that the cardiac enzymes were within normal limits, simply indicates that the ischemia was transient and did not persist for sufficient time to irreversibly...

Prevention strategies whole populations highrisk groups or selected individuals

That second issue goes further than that. As Rose eloquently pointed out, those factors that best explain the occurrence of cases within a population may not best account for the rate of the disease within the population at large. For example, if the population, overall, consumes a high-fat diet, then whether or not an individual smokes cigarettes may best explain whether he she develops coronary heart disease. Meanwhile, the population-wide dietary behavior may be the main source of the elevated rate of coronary heart disease within that population. Consider another example, admittedly extreme, but it helps to make the point. If within a population everyone smoked 20 cigarettes per day, then the prime determinant of individual risk of lung cancer might well be one or more genetic polymorphisms which determine the fate of inhaled carcinogens. Yet it is the smoking that accounts for the overall high rate of lung cancer in that hapless population.

Epidemiological Triad

Another way to visualize these influences is using the classic epidemiological triad (Fig. 2), which has proved to be a robust model with epidemics such as infectious diseases, smoking, coronary heart disease, and injuries (25-27). The Host in Figure 2 encompasses the biological and behavioral influences and the physiological moderators of weight change from the ecological model. The Agent is defined as positive energy balance, and its Vectors are energy-dense food, large portion sizes, timesaving machines (e.g., cars) and time-using machines (e.g., television). These are analogous to the mediators. The Environment is the same in both models. The strategies for intervention are different for each corner of the triad however, the main lesson learned from other epidemics is that all three corners need to be addressed together. For the host, the intervention strategies encompass both prevention and treatment and range from education (awareness raising to intensive counseling), through...

Ivwhy The Focus On Environments

Obesity, like diabetes and coronary heart disease, has higher prevalence rates among the lower-socioeconomic status (SES) populations in developed countries. Low income and low educational attainment bring reduced options for low-SES groups and a lower uptake of health messages about behavioral changes for a healthy future. One of the key strengths of an environmental focus is its potential impact among lower-SES groups. By influencing the ''default'' choices in key environments, there is a much greater potential to affect overall diet and physical activity patterns in lower-SES groups than by education strategies alone. Education-based campaigns are complementary to the environmental approach, but the priority needs to be on ensuring that the healthy choices are available first, before embarking upon such campaigns to educate people about taking up those choices.

Peter A Mayes PhD DSc Kathleen M Botham PhD DSc

Unsaturated fatty acids in phospholipids of the cell membrane are important in maintaining membrane fluidity. A high ratio of polyunsaturated fatty acids to saturated fatty acids (P S ratio) in the diet is a major factor in lowering plasma cholesterol concentrations and is considered to be beneficial in preventing coronary heart disease. Animal tissues have limited capacity for desaturating fatty acids, and that process requires certain dietary polyunsaturated fatty acids derived from plants. These essential fatty acids are used to form eicosanoic (C20) fatty acids, which in turn give rise to the prostaglandins and thromboxanes and to leukotrienes and lipoxins known collectively as eicosanoids. The prostaglandins and thromboxanes are local hormones that are synthesized rapidly when required. Prostaglandins mediate inflammation, produce pain, and induce sleep as well as being involved in the regulation of blood coagulation and reproduction. Nonsteroidal anti-inflammatory drugs such as...

The Hypoxic Tumor Microenvironment Angiogenesis And Edema

Maintaining the body's pO2 constant is absolutely essential for mammalian life. A highly developed, multilevel physiological system is devoted to the body's oxygen homeostasis. One of the first physiological systems to be established during development is the blood circulation. Failure in cardiac, erythroid, or vascular development leads to early embryonic lethality, suggesting that in multicellular organisms, oxygen as well as nutrients need to be delivered by a functional circulatory system. Mammalian cells are located within a distance of 100-200 mm (the diffusion limit of oxygen) from blood vessels. To grow beyond this size, multicellular organisms and tissues need to recruit new blood vessels by vasculogenesis and angiogenesis. The establishment of a highly branched vascular system is regulated by a balance between pro- and anti-angiogenic factors. This finely tuned balance is disturbed in various diseases including some of the leading causes of mortality in the West such as...

Problems Associated With Adenoviral Retargeting In The Field Of Cancer Gene Therapy And Current Efforts

In 1995, the National Institutes of Health (NIH) director designated a special advisory panel headed by Drs. Orkin and Motulsky which produced a report about the limiting issues in the field of gene therapy and the points in the report are still valid (81). One of the main points was that vector systems still have problems and need to be improved to realize the benefit of gene therapy. Recently there have been several promising reports indicating the clinical benefits of gene therapy in severe combined immunodeficiency mice (SCID) (82) and cardiovascular disease (83,84), yet, the realization of the clinical therapeutic potential of the cancer gene therapy has not been achieved.

Broad etiological groups

Genes identified as mutated in syndrome congenital heart disease Rapid progress has been made over the last 15 years in identifying the genes underlying many monogenic malformation syndromes giving clues to some of the genes critical for development of specific organs (Donnai and Read, 2003). As an example, genes known to underlie the pathogen-esis of syndromic congenital heart disease are given in Table 13.3. Although numerically small in terms of their contribution towards morbidity and mortality, description of their pathogenesis has contributed disproportionately to the understanding of normal embryogenesis and has consequently set the stage for investigation of more complex disorders. The roles that epigenetic mechanisms play in the genesis of malformations remain a relatively unexplored and unappreciated area although they are implicated in disorders characterized by defects in imprinting (Paulsen and Ferguson-Smith, 2001) and underlying some developmental defects...

Suggested Readings

Cardiovascular disease in diabetic patients. Med Clin North Am. 2000 84 81-93. diabetic cardiomyopathy. There is left ventricular hypertrophy, extensive multifocal myocytolytic necrosis (the darker areas in the subendocardium and mid-wall), and multifocal fibrosis (the paler areas involving the papillary muscle, trabeculae, and ventricular wall). The recent and organizing necrosis, together with remote scarring, leads to replacement of large areas of functional myocardium, equivalent to myocardial infarction. diabetic cardiomyopathy. There is left ventricular hypertrophy, extensive multifocal myocytolytic necrosis (the darker areas in the subendocardium and mid-wall), and multifocal fibrosis (the paler areas involving the papillary muscle, trabeculae, and ventricular wall). The recent and organizing necrosis, together with remote scarring, leads to replacement of large areas of functional myocardium, equivalent to myocardial infarction.

Applying the Framework for Comparing Cities Health Services and Health to Four World Cities

WCP has applied elements of the framework presented earlier to study four dimensions of health and access to health care in four world cities infant mortality, coronary artery disease (CAD), avoidable hospital conditions (AHC), and patterns of aging, quality of life and use of long-term care services. Our study on the prevalence and treatment of CAD examined mortality, morbidity and treatment patterns for acute myocardial infarction, and other forms of CAD in New York, London, and Paris (Gusmano, et al., 2004). We explored the relationship between the health system and neighborhood characteristics and the

Cardioprotective Effects

Considering that GSE demonstrates antioxidant, antiplatelet and anti-inflammatory actions, it may have a role in the prevention of cardiovascular disease. A number of researchers have investigated this issue further, mainly using animal models. One series of studies was conducted by Bagchi et al (2003) using a natural, standardised, water-ethanol extract made from California red grapeseeds, which contained Grapeseed extract 646

Body Fat Distribution

In a recent study in Singapore we found that the relative risk for having at least one cardiovascular risk factor (e.g., elevated cholesterol, hypertension, diabetes mellitus) is elevated at levels of WC or WHR far below the WHO cutoff points (50). Using WHO cutoff points for classification of abdominal obesity (30) would miss a large part of the population at risk. This elevated risk could be due to a higher amount of visceral fat at low WC or to other factors, e.g., genetic factors. Further studies in Singapore are needed to determine the relationship between anthro-pometric measurements (WC and WHR) and the amount of visceral fat by CT or MRI.

Cardiovascular Protection

Epidemiological studies suggest that green tea consumption is associated with a reduced risk of cardiovascular disease (Maeda et al 2003). A 2000 prospective cohort study of 8552 people in Japan found that those consuming more than 10 cups per day, compared with those consuming fewer than 3 cups, had a decreased relative risk of death from cardiovascular disease (Nakachi et al 2000). One cross-sectional study involving 1371 men aged over 40 years found that increased green tea consumption was associated with decreased serum concentrations of total cholesterol and triglyceride and an increase in HDL, together with a decrease in LDL- and VLDL-cholesterols (Imai & Nakachi 1995).

Non Cancer Health Care and Health Maintenance

The IOM report suggested in its title that many cancer survivors are lost in transition and that the quality of care suffers when patients and providers do not know what is expected after primary treatment ends. While much of the focus of research and guidelines has been on cancer surveillance, non-cancer health care is equally as, and in many cases more important than surveillance. Most patients diagnosed with cancer today are expected to survive it.28 Studies have shown that potentially preventable conditions like heart disease and diabetes are actually the greatest threat to life for many of these patients.83,84 As a result, despite the fact that a diagnosis of cancer tends to subjugate all other concerns for a while, preventive care and the management of other medical conditions may actually be more important in the long run.

Pharmacological Toxicological Effects 51 Cardiovascular Effects

Results from a study in nine subjects found that supplementation with AGE at a dose of 2.4g day significantly inhibited the oxidation of LDL, but ingesting 6 g day of crushed raw garlic did not have a significant effect. The authors believe that this difference in response may be owing to the fact that the active ingredient in raw garlic is allicin, whereas SAC is believed to be the active component of AGE in preventing atherosclerosis. However, when compared to a-tocopherol (Vitamin E), which is well documented at preventing lipid oxidation, both AGE and raw garlic were less effective at inhibiting oxidation (p < 0.05) (12). In addition, it has been shown that 900 mg day of garlic powder vs placebo for 4 years caused a significant decrease in arterio-sclerotic plaque volume in both men and women with advanced atherosclerotic plaques and at least one cardiovascular risk factor (13). A recent meta-analysis using multiple databases, from inception until November 1998, compiled all...

Barriers to Creating a Formal Survivorship Care Plan

Cancer survivors make more office visits for cancer care with PCPs than with oncologists.90 While this may often be due to insurer mandates or specialist availability, it is important to optimize the opportunity this presents. Oncologists often lack the time to adequately provide all care to all cancer patients and survivors. Moreover, there is not sufficient manpower to sustain an entirely specialist-based model of survivor care given the nation's growing population of cancer survivors. PCPs are better positioned and qualified to ensure that the full spectrum health needs of cancer survivors are addressed, including not only issues surrounding their cancer but also health maintenance (prevention), the management of concurrent comorbid disease (e.g., heart disease, diabetes), mental health,

Preoperative laboratory evaluation

Hemoglobin menstruating females, children less than 6 months or with suspected sickle cell disease, history of anemia, blood dyscrasia or malignancy, congenital heart disease, chronic disease states, age greater than 50 years (65 years for males), patients likely to experience large blood loss.

Management Of Risk Factors In Overweightobese Persons

In patients who are overweight obese, clinical focus should be directed first to the risk factors associated with obesity. Most of these risk factors relate to cardiovascular disease, but some may indicate an increased susceptibility to type 2 diabetes. Management of the metabolic risk factors that are characteristic of the metabolic syndrome will be discussed. However, consideration will be given first to management of elevated low-density lipoprotein (LDL) cholesterol, which is the prime risk factor for development of atherosclerotic coronary heart disease.

Somatic Cardiac Abnormalities

May contribute to the high incidence of arrhythmias in the chagasic heart. Substantial changes in gap junction expression are also reported following experimental myocardial infarction in rodents and larger mammalian species, such as the dog. Most reports describe a relative loss and or reorganization of Cx43 within the epicardial border zones, a disturbance that may facilitate the development of reentrant ventricular tachycardia (Luke et al., 1991 Matsushita and Takamatsu, 1997 Peters et al., 1997). Downregulation of Cx43 has also been observed at sites distant from the infarct, although in contrast to epicardial border zones, the subcellular localization appears unchanged from normal myocardium. Similar quantitative and qualitative alterations in gap junction expression have also been observed in tissue samples taken from humans with either ischemic or hypertrophic heart disease (Peters, 1996 Severs, 1994 Kaprielian et al., 1998), supporting the utility of these animal models to...

Vasculature Segmentation Techniques

Kim et al. 11 imaged the proximal coronary artery vessel wall with highresolution 3-D cardiovascular MRI. The proximal vessel wall and lumen boundaries were obtained using an automated edge detection tool. Comparison of vessel wall thickness and luminal diameter between healthy subjects and patients with coronary artery disease showed increased wall thickness and but no significant difference in luminal diameter in patients. This was due to positive arterial remodeling in the patients, known as the Glagov effect. Yuan et al. 34 further showed that identification of a ruptured fibrous cap in in-vivo human carotid atherosclerosis using high-resolution MRI is highly associated with a recent transient ischemic attack (TIA) or stroke. Multiple contrast-weighted MR protocol was used to obtain the images. The fibrous caps were reviewed and classified as either being intact and thick, intact and thin, or ruptured. Patients were classified as symptomatic or asymptomatic depending on recent...

Role for NMR in Toxicogenomics

Compared to microarrays, differential display technology, and 2-dimensional (2D) gel electrophoresis-mass spectrometry 4 , NMR has been established over the last two decades as a valuable tool for researching the molecular basis of toxicity. The exploratory nature of the technique has led to success in relating certain pathologies to underlying mechanisms of disease, including inborn errors of metabolism and coronary heart disease 6-8 . The increasing use of NMR in clinical settings is thus envisaged in the coming years. With this evolution comes the possibility of investigating toxicological pathologies directly in a hospital environment. Wide-ranging applications of NMR in toxicology already include the clinical diagnostics described above, evaluating suitable animal models for biomarkers of toxicity 9,10 , detecting silent phenotypes in genetic models 11, 12 , and assessing environmental toxicity 13-15 .

Physical Examination

Physical examination is often of great importance in clarifying suspected etiologies. Start with a general examination, and keep in mind some of the vascular, endocrinological, and neurological causes of ED. Assess the degree of androgen-ization checking for body hair and any evidence of gynecomastia. Examine the genitalia carefully for any abnormalities. Check whether the foreskin can be retracted, and look for conditions such as phimosis or balanitis. Deep palpation of the penis can reveal fibrotic thickening (Peyronie's plaques) in a proportion of men presenting to sexual dysfunction clinics. Cremasteric and bulbocavernous reflexes should be elicited as well as saddle sensation and deep tendon reflexes of the legs. The size and consistency of the testicles should be assessed. If urinary symptoms are present, rectal sphincter tone and prostatic examination are necessary. Cardiovascular risk assessment should be undertaken see Appendix and Jackson et al. (17) .

MtDNA Damage and the Mitochondrial Theory of Aging

Several lines of evidence indirectly implicate mtDNA in longevity. The Framingham Longevity Study of Coronary Heart Disease has indicated that longevity is more strongly associated with age of maternal death than that of paternal death, suggesting that mtDNA inheritance might be involved. On the other hand, longevity was shown to be associated with certain mtDNA polymorphisms. For instance, Italian male centenarians have an increased incidence of mtDNA haplogroup J, whereas French and Japanese centenarians have increased incidences of G to A transition at mt9055 and C to A transversion at mt5178, respectively. However, a study of an Irish population failed to link longevity to any particular mitochondrial haplotype, suggesting that factors other than mtDNA polymorphism also may play a role in aging (Ross et al., 2001).

Anticoagulants Evaluated for Treatment of HIT

2005 Hursting et al., 2005) Patients undergoing renal replacement therapy (Reddy et al., 2005) Patients with renal dysfunction (Guzzi et al., 2006) Patients with hepatic dysfunction (Levine et al., 2006) Patients who are critically ill (Gray et al., 2007) Patients with coronary artery disease (Jang et al., 2007) Cost-effectiveness analysis (Arnold et al., 2006)

Contraindications

These drugs should be administered with caution to patients with cardiac, renal, or hepatic diseases. In patients with severe impairment of renal function, a test dose (0.2g kg of body weight, to produce urine flow of at least 30 to 50mL h) should be performed by the internist prior to use of intravenous mannitol. Caution should be exercised, in particular, in patients with congestive heart disease, hypervolemia, electrolyte abnormalities, confused mental states, and dehydration. Oral glycerol should be used with caution in diabetic patients because the blood glucose may rise after metabolism of the drug. When osmotic drugs are administered prior to surgery, the patient's bladder should be empty.

Agerelated Changes in Hormones and Their Receptors in Animal Models of Female Reproductive Senescence

Traditionally, the onset and progression of menopause in humans has been attributed to ovarian follicular decline. Because the follicles are the primary source of circulating estrogens, these age-related changes lead to a number of symptoms such as hot flashes, mood swings, irritability, and depression, as well as increased risk of osteoporosis, cardiovascular disease, and age-associated diseases. Recent research indicates that along with the ovarian changes at menopause, the hypothalamic and pituitary levels of the reproductive axis also undergo significant changes during reproductive aging. Indeed, current research suggests a neural, as well as hormonal, mechanism involved in the menopausal process. A number of animal models are available to study these processes, most commonly the nonhuman primates and rodents, and to a lesser extent, avian systems. Here, we will discuss Old and New World monkey models, rats, mice (wild type, transgenic, and genetically modified), and birds as...

Treatment for Priapism

For erections lasting over 4 h, apply cooling agents to the genitals and encourage moderate exercise to the legs to divert blood to the lower limbs. If the erection remains, aspirate 20-50 mL of blood from the corpus cavernosum using a 19 -21 gage butterfly using a sterile technique. This may be followed by irrigation with heparinised saline. If necessary, repeat to the other side. If there is no response proceed to ICI alpha-adrenergic agents. Either phenylephereine 10 mg (1 mL) vial diluted to 10 mL with saline and 0.5 mg (0.5 mL) injected at a time to a maximum of 10 mg (10 mL) or ephedrine 30 mg in 1 mL vial, using 15 mg (0.5 mL) should be given, and repeated once if necessary. Monitor pulse and BP continuously. Proceed with extreme caution in patients with coronary heart disease, uncontrolled hypertension, or cerebral ischemia and in men taking MAOIs as hypertensive crises may occur. See also the latest AUA guidelines (104).

Clinical Use of Lepirudin

Besides its use in patients with HIT, lepirudin has been investigated extensively in controlled clinical trials for acute coronary syndrome (ACS) (n > 14,000), including MI (Antman, 1994 Neuhaus et al., 1994) and unstable angina pectoris (Rupprecht et al., 1995 Organization to Assess Strategies for Ischemic Syndromes OASIS-2 , 1999) and in pilot studies for prophylaxis and treatment of DVT (Parent et al., 1993 Schiele et al., 1997). In patients undergoing hemodialysis (see Chapter 18) or cardiac surgery (see Chapter 19), there is observational evidence indicating safe and effective use of lepirudin. Results of three prospective clinical trials with lepirudin and an extensive postmarketing drug monitoring study in HIT patients treated in the real-world setting are described in the next section.

Krzisnik Krk Longevity

Khaw, K.T., Wareham, N., Bingham, S., Luben, R., Welch, A., and Day, N. (2004). Association of hemoglobin A1c with cardiovascular disease and mortality in adults The European prospective investigation into cancer in Norfolk. Ann. Intern. Med. 141, 413-420. Rosen, T., and Bengtsson, B.A. (1990). Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336, 285-288.

Conduction System

Serratus Anterior

Angina pectoris most commonly is caused by atherosclerotic disease. It results from myocardial ischemia that falls short of inducing cellular necrosis. Clinical findings include pain that is precipitated by exertion, but relieved by rest a sensation of pressure or burning in the chest that may last as long as 20 minutes pain radiating to the arm, jaw, and neck and tachycardia. 2. Acute myocardial infarction (MI heart attack) most commonly is caused by atherosclerotic disease. It results from myocardial ischemia that induces cellular necrosis. Clinical findings include onset at rest (usually) a sensation of pressure or burning in the chest that lasts longer than 30 minutes pain radiating to the arm, jaw, and neck nausea or vomiting sweating shortness of breath and tachycardia. Mis may be silent and without consequence. Complications of MI include congestive heart failure papillary muscle rupture, indicated by acute onset of congestive heart failure with...

Deadly infections worldwide

The World Health Organisation in its 1996 report 8 estimated that the leading cause of approximately 50 million deaths in the world in 1995 was infectious diseases, which accounted for about one-third or 17 million deaths. Other figures included diseases of the circulatory system (15 million deaths including ischaemic heart disease 7.2 million and stroke 4.6 million) and cancer 6.2 million deaths (approximately 12 ).

Body Size At Birth And Later Body Composition

People who had low birth weight tend to accumulate fat on the trunk and abdomen, a pattern of adiposity found in the insulin resistance syndrome in which central obesity, impaired glucose tolerance, hypertension, and altered blood lipid concentrations occur in the same patient (9). This disorder is associated with an increased risk of coronary heart disease (10). In two studies in the United Kingdom men who had low birth weight had high ratios of waist-to-hip circumference after allowing for adult body mass index (Table 1) (11). This association with low birth weight has been replicated in a study of men in Sweden (12). In the Swedish study birth weight was also associated with truncal fat, as measured by a high ratio of subscapular to triceps skinfold thickness. After allowing for current body mass index truncal fat increased by 0.30 standard deviations with each kilogram decrease in birth weight.

Pain control and medicines

Blood products and plasma expanders (section 11 of the Model list), Cardiovascular disorders (section 12), and Fluid and electrolyte balance (section 26) are further explained in section 5.3 of these guidelines, on the topic of Circulation. The isotonic crystalloid solutions constitute the mainstay of resuscitation of hypotensive trauma patients, and their availability and appropriate use should be assured in every hospital where severely injured patients are treated. Although dopamine is considered to be an essential medicine in the Model list, the Guidelines for essential trauma care list it as desirable, because of the cost involved in adequately training both medical and nursing staff in the safe administration of pressors by continuous IV infusion. Cardiovascular disorders (WHO EML section 12)

B CPB and Vascular Surgery

Koster and colleagues (2000b) used lepirudin instead of heparin in 57 patients who had clinically diagnosed HIT and required CPB. The primary diagnoses included coronary artery disease (n 27, including eight cases of MI), valvular heart disease (n 14), combined coronary artery and valvular disease (n 9), thoracic aortic aneurysms (n 4), ventricular septal defect resulting from MI (n 2), and atrial tumor (n 1). In that study, anticoagulation was monitored with ECT, and lepirudin was maintained in the range of 3-4 mg mL. The dose requirement for CPB was 0.016-0.035 mg kg min (1.0-2.1 mg kg h), with concurrent 24-h blood drainage of 50-2200 mL. Elimination of the drug at the conclusion of CPB was augmented through modified zero-balanced ultrafiltration and forced diuresis. However, drug removal was dependent on the prevailing renal function. Four patients with impaired renal function showed prolonged elimination and bleeding. Of the 57 patients, 54 achieved full recovery and showed no...

Lipid and Lipoprotein Metabolism

Consistently studies have demonstrated that adults with GH-deficiency have elevated concentrations of total cholesterol, low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (ApoB) compared with an age and sex matched control population or the predicted range (25,53,54). Characteristically, high density lipoprotein-cholesterol (HDL-C) is reduced and triglyceride (TG) concentrations are elevated compared with healthy controls (55). Therefore GH-deficiency is associated with a lipid profile recognized to be associated with premature atherosclerosis and cardiovascular disease.

Table 201 Therapy of ischemic heart syndromes

Eptifibatide 180 g kg bolus followed by 2 g kg min for up to 72 hours. Acute Myocardial Infarction peptide antagonist, reduced myocardial infarctions and deaths when used with heparin and aspirin in unstable angina patients. Abciximab has also been used for this indication but is only effective if percutaneous coronary intervention (PCI) is planned. Surprisingly, abciximab when used without PCI for unstable angina appears to be inferior to heparin and aspirin.

Effect of GH Replacement on Plasma Lipids and Lipoproteins in GHDeficiency

The major exception to the trend of beneficial effects on cardiovascular risk factors with GH replacement is lipoprotein (a) concentration, a proposed independent risk factor for the development of atherosclerosis and myocardial infarction (62). In studies of the effect of GH treatment, lipoprotein (a) levels rose in four of five studies (57-60). The importance of this observation is not yet known.

Relationship With Disability And Diseases

Diseases alone (e.g., subclinical cardiovascular disease (Newman et al., 2001), chronic renal insufficiency (Shiplak et al., 2004), or in combination (i.e., comorbidity)) are associated with frailty. In the CHS study, only 7.3 of frail subjects had no chronic disease compared to 23.2 in those who were not frail (Fried et al., 2001). Sixty-eight percent of frail individuals had two or more chronic conditions compared to 40 in the not frail group (Fried et al., 2001). It should be noted, though, that it was a small proportion of those with comorbidities (10.5 ) who were also frail (Fried et al., 2001). Nearly all frail individuals will have at least one chronic condition, and most will have two or more. The presence of comorbid-ities, though, is not specific for frailty.

Occupational exposure

A retrospective study ofthe effects ofoccupational exposure to carbon monoxide on mortality from heart disease (Stern et al., 1988) found that tunnel officers had higher mortality from arteriosclerotic heart disease than people in the general population ofNew York City (standardized mortality ratio (SMR) 135 90 CI 109-168). Tunnel officers also had a higher risk ofmortality from arteriosclerotic heart disease than the less-exposed bridge officers, which leads to the hypothesis that motor exhaust might increase the risk of myocardial infarction. A prospective study on mortality of professional drivers in London particularly lorry drivers showed excess deaths from stomach cancer, lung cancer, bronchitis, emphysema and asthma, although there were significantly fewer deaths than expected from all causes and circulatory diseases (Balarajan & McDowall, 1988). This pattern, however, could not be confirmed in taxi drivers. The possible relationship between occupational exposure to vehicle...

Table 204 Risk of strokeyear in patients with atrial fibrillation

Data now exists to risk-stratify patients and help the clinician choose between warfarin and aspirin. As shown in Tables 20.3 and 20.4, the SPAF study found 3 clinical and 2 echocardiographic findings which can segregate patients into high-and low-risk groups. Patients with a stroke risk of 1-2 (under age 75) should be considered for aspirin therapy and the high-risk patients (risk greater than 10 ) should receive warfarin. Patients without risk factors for bleeding and with one risk factor for embolism should be considered for warfarin therapy. Their risk of stroke is higher than the risk of serious hemorrhagic complications of warfarin. A subgroup analysis from SPAF suggests that warfarin protects against embolic stroke while aspirin protects against non-embolic stroke in patients with atrial fibrillation. In low-risk

Study Of Tamoxifen And Raloxifene

The results of the STAR trial are expected by 2006. Clearly, it will be invaluable to establish the overall benefits of the drugs with regard to breast cancer incidence, coronary heart disease, and osteoporosis. Comparisons of endometrial cancer will be especially interesting because the standard of care, i.e., self-reporting, will be employed in the STAR trial rather than routine screening with annual biopsies.

Atrial Fibrillation Special Situations

Atrial fibrillation in thyrotoxic heart disease is associated with a high rate of embo-lic phenomena. Therefore, these patients should receive warfarin to maintain an INR of 2.0-3.0 until 4 weeks after the resumption of normal sinus rhythm. Patients with risk factors such as atrial fibrillation, previous embolism or coronary artery disease should be considered for combined therapy.

Clinical Use of Argatroban

Argatroban therapy has been evaluated, in addition to HIT, in acute myocardial infarction (Theroux, 1997 Jang et al., 1999 Vermeer et al., 2000), unstable angina pectoris (Gold et al., 1993), peripheral arterial obstructive disease (Matsuo et al., 1995), stroke (Kobayashi and Tazaki, 1997 LaMonte et al., 2004a Sugg et al., 2006), PCI (Herrman et al., 1996 Jang et al., 2004), and hemodialysis (Murray et al., 2004). In each of these settings, argatroban produces predictable anticoagulant effects and is generally safe and well tolerated. In addition to its indications in HIT, argatroban is approved outside the United States for use in nonlacunar stroke (Japan, South Korea), chronic arterial occlusion (Japan, South Korea, China), and hemodialysis of antithrombin-deficient patients (Japan).

Table 206 Risk for embolic events when off anticoagulation Pauker JAMA

Antman EM. 'I can see clearly now' a new view on the use of IV GP IIb IIIa inhibitors in acute coronary syndromes. Eur Heart J 2002 23(18) 1408-11. 4. Braunwald E, Antman EM, Beasley JW et al. ACC AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction summary article J Am Coll Cardiol 2002 40(7) 1366-74. 5. Brogan GX Jr. Bench to bedside pathophysiology of acute coronary syndromes and implications for therapy. Acad Emerg Med 2002 9(10) 1029-44. 6. Chan AW, Moliterno DJ. Defining the role of abciximab for acute coronary syndromes lessons from CADILLAC, ADMIRAL, GUSTO IV, GUSTO V, and TARGET. Curr Opin Cardiol 2001 16(6) 375-83. 10. Kereiakes DJ, Montalescot G, Antman EM et al. Low-molecular-weight heparin therapy for non-ST-elevation acute coronary syndromes and during percutaneous coronary intervention an expert consensus. Am Heart J 2002 144(4) 615-24. 11. McKay RG, Boden WE. Small peptide GP IIb IIIa receptor...

The Future Of Prevention

Another unexplored aspect of chemoprevention with tamoxifen is evaluation of lower doses. This strategy may reduce side effects, while maintaining protection for the breast. Pilot studies have been completed in Italy,235,236 and clinical trials with large populations are planned. Finally, a new generation of agents that specifically modulate ERa and ERjS selectively may become available for clinical testing within the next decade.233 A number of postmenopausal diseases will be targeted, such as osteoporosis and coronary heart disease but the beneficial side effects should include a reduction in uterine and breast cancers in the general population.237 The present reduction of breast cancer in high-risk women by 50 is an important first step that has resulted from the rational application of translational research.

Table 212 NINDS trial criteria for tPA

An ischemic stroke with a clearly defined time of onset, Patients who do not undergo thrombolytic therapy and do not have an obvious embolic source for their stroke should be started on aspirin. Two large trials have shown a small but real benefit of aspirin in preventing death or disability. Since patients with stroke also have risk factors for ischemic heart disease the aspirin will be of benefit for this as well. Clopidogrel can be substituted in the aspirin-intolerant patient. Currently the combination of aspirin and clopidogrel is being examined in a large trial to see if it has any advantage over single drug therapy. A frequent cause of morbidity and mortality in the stroke patient is deep venous thrombosis and pulmonary embolism. Stroke patients should receive prophylaxis with low molecular weight heparin which has been shown to be safe and effective in these patients and does not increase the risk of bleeding. Transient Ischemic Attacks Patent foramen ovale (PFO) exists in 20...

Factors Unique To Older Minorities

More importantly, the profiles of disease and disability vary substantially across ethnic and cultural groups. Whereas the most prevalent chronic conditions among older non-Hispanic whites are cardiovascular disease, stroke, and cancer, African American elderly evidence elevated rates of hypertension and renal disease, and Hispanic elderly evidence increased rates of diabetes, cirrhosis, and gallbladder disease (Fried & Wallce, 1992 Markides, Rudkin, Angel, & Espino, 1997). Differences in disability rates are also apparent. In comparison to older non-Hispanic whites, for example, older African Americans and Hispanics appear to experience greater rates of disability, whereas the rates among older Asian Americans appear to be lower (Guralnik & Simonsick, 1993). Differences in other factors such as health behaviors associated with mental disorders are also evident. Older African American males, for example, have higher rates of smoking, and older Hispanics have elevated rates of...

Table 214 Blue toe syndrome after OKeefe

Albers GW, Amarenco P, Easton JD, Sacco RL, Teal P. Antithrombotic and thrombolytic therapy for ischemic stroke. Chest 2001 119(1 Suppl) 300-320. 5. Johnston SC. Clinical practice. Transient ischemic attack. N Engl J Med 2002 347(21) 1687-92. 9. Mohr JP, Thompson JL, Lazar RM et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Med 2001 345(20) 1444-51.

Development Of Overweight

The argument that fetal life represents a critical period for adiposity has not been totally resolved, the evidence from the infants of mothers with diabetes notwithstanding. Several large studies have shown an association between high birth weight and child adiposity (75-78) or adult adiposity after controlling for gestational age (77,78), but most did not adjust for confounding variables such as parental fatness, maternal smoking, gestational diabetes, or socioeconomic status (79). Conversely, low birth weight may be associated with an increase in intra-abdominal fat deposition that may in turn account for an increased likelihood of risk factors for cardiovascular disease, including hypertension, diabetes, and hyperlipidemia (80). However, the association between lower birth weight and the development of overweight has not been clearly demonstrated. Although babies with lower birth weight have been shown to have an increased risk of syndrome X and of heart and pulmonary disease in...

HIV and Cardiac Diseases

New and effective antiretroviral drugs have decreased the mortality of HIV infection. However, antiretroviral therapy (ART) is not without side effects. It is expected that the risk of cardiac and cardiovascular diseases will rise in the following years due to the elevated cardiovascular risk profile and increased life expectancy of HIV-infected patients (Fisher 2001, Neumann 2002a). Therefore, diagnosis and therapy of HIV-associated cardiovascular diseases should become an inherent part of current therapeutic concepts of HIV infection.

Case 20 Clinical Summary

A 38-year-old African American man presented to the emergency room with shortness of breath, chest and abdominal pains of 4 days duration. An electrocardiogram (ECG) revealed acute antero-lateral myocardial infarction and a conduction delay with A-V dissociation. He was in shock with low cardiac output and renal insufficiency. His physical exam on admission was significant for tachycardia (100-110 ppm), hypotension (80 50 mmHg), an S3 gallop and bilateral rales up to mid-lung fields. The diagnosis of acute CHF secondary to an acute myocardial infarction was made. He was treated with dobutamine, furosemide and oxygen. Shortly after endotracheal intubation he developed cardiac tachyarrhythmias with subsequent electromechanical dissociation. Resuscitation was unsuccessful.

Augmentation And Novel Treatment Strategies

Although patients who receive ECT tend to be older than those who do not (de Carle et al., 2000), there are few good studies of the use of ECT in the elderly population. ECT has been reported to be effective in elderly patients in several open or retrospective case series (Bosworth et al., 2002 Kujala et al., 2002 Little et al., 2004), with improvement in about 80 and adverse events in about 35 (Kujala et al., 2002 Little et al., 2004). Safety has been generally acceptable, with only minor complications during ECT among older patients with preexisting cardiovascular disease falls are reported with increasing frequency as the number of treatments increases (de Carle et al., 2000).

Diseases of the heart

In 245 patients with dilated cardiomyopathy characterized by unexplained left ventricular dysfunction, viral genomes were amplified by PCR in endomyocardial biopsy samples from 165 (67.4 ) of the 245 patients (Kuhl et al., 2005). HHV-6 was detected in 53 (21.6 ), and this was second in frequency to parvovirus B19, which occurred in 126 patients (51.4 ). Other viruses, including adenovirus and enterovirus, occurred at lower frequency. Multiple infections occurred in 45 samples (27.3 ) with 26 (15.8 ) showing coinfection with parvovirus B19 and HHV-6. Active or borderline myocarditis according to the Dallas criteria was not present in any case. Also, lymphocyte and macrophage infiltrates were not significantly different in virus-positive and virus-negative patients. Similar recovery of virus has not been reported in normal hearts of multiorgan donors or patients with valvular heart disease. The findings in the patients with idiopathic left ventricular dysfunction suggest that viral...

Conclusion for clinicians

HIV patients suffering from exercise-induced dyspnea should be tested for pulmonary hypertension when other pulmonary or cardiac diseases (e.g. restrictive or obstructive ventilation disorders, pneumonia, coronary heart disease) have been excluded. The incidence of pulmonary hypertension is elevated by a factor of 1,000 in HIV patients compared to the general population. Estimated numbers of unreported cases are not included.

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