Natural Treatment to Reverse Cardiovascular Disease

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. Read more here...

The Big Heart Disease Lie Summary


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Acute coronary syndromes

Acute coronary syndromes include unstable angina, non-ST-segment elevation MI (NSTE MI) and ST-segment elevation MI (STE MI) (Santiago and Tadros, 2002). It is acknowledged that with revised definition of myocardial infarction, diagnosed by cardiac troponin estimation, there will be a resultant increase in the reporting of myocardial infarction, with increased workloads for the services involved (Dalal, et al, 2004). In the Cochrane systematic review by Jolliffe, et al. (2004) the reviewers concluded that exercise-based CR is effective in reducing cardiac deaths and has many positive health-related outcomes for post-MI and CHD groups.

Congenital heart disease

The patient group includes children and young people. Exercise and physical activity levels are dependent on the differing types of congenital heart disease. There may be barriers to exercise in this group, such as current symptoms, lack of interest in exercise and health fears (Swan and Hillis, 2000). A review by Brugemann, et al. (2004) found that patients with congenital heart disease should be included in multidisciplinary CR. In addition, physical training was found to be safe. A pre-training exercise test is required to determine specific and appropriate physical workload. Furthermore, education, psycho-social support and coping strategies to help reduce anxiety are essential parts of CR for this patient group. Paediatric specialists have advocated exercise-training programmes for children with congenital heart disease. A review of literature by Imms (2004) suggests that CR programmes for children should also promote occupational performance activity and integrate exercise into...

Congenital Heart Disease Introduction

Congenital heart disease results from malformations of the heart that involve the septums, valves, and large arteries. They are classified as acyanotic or cyanotic defects. Acyanotic defects occur when a left-to-right shunt is present that allows a mixture of oxygenated and unoxygenated blood to enter the systemic circulation. The most common consequences of these defects in children are growth retardation and congestive heart failure (CHF).

Finding Genes for Cardiovascular Disease

Genetics studies of cardiovascular disease involve searches for genes in two general classes causative genes and disease-susceptibility (or disease-modifying) genes. These are sought through gene-linkage analysis or candidate-gene studies, respectively. Identifying causative genes for this disease is likely several years away at best. Before that time, however, a new understanding will have been reached regarding the relationship between inherited risks and outcomes in cardiovascular disease. With the development of new technology, we also have the promise of a detailed catalogue of disease-modifying genes that may open the door to therapeutic advances. Gene-linkage analyses involve the study of families that express the cardiovascular trait of interest. In such studies, it is important also to establish the relative risk. Relative risk is defined as the probability of developing a condition (such as cardiovascular disease) if a risk factor (such as a gene) is present, divided by the...

Cardiovascular Disease

Cardiovascular disease accounts for approximately 60 of deaths in acromegaly (25) and is the most significant predictor of mortality. Coexisting hypertension and coronary artery disease occur (25-29), in addition to a specific GH IGF-1-mediated cardiomyopathy (25). Twenty percent of patients have symptomatic heart disease, expanded extracellular fluid volume owing to sodium and fluid retention, arterial hypertension, accelerated atherosclerosis, and cardiac arrhythmias. Fifty percent of patients have hypertension, with evidence of left-ventricular dysfunction in half (29).

Mri In Acute Ischemic Stroke

Flair Mri Cerebral Infarction

Stroke is the third leading cause of death after myocardial infarction and cancer, the leading cause of permanent disability in western countries (WHO Guidelines Subcommittee, 1999), and the leading cause of disability-adjusted loss of independent life years. In addition to the tragic consequences for patients and their families, the socioeconomic impact of disabled stroke survivors is estimated to be between 35,000 and 50,000 per survivor, per year. In the face of our aging population, the incidence and prevalence of stroke are expected to rise. Therefore, an effective and widely available treatment for this devastating disease is desperately needed. Before the development of MRI and continuing until the early 1990s, the stroke field was dominated by therapeutic nihilism. Patients were treated conservatively and sent to rehabilitation units or nursing homes. Major stroke trials performed during that time focused on secondary prevention. These included two trials of carotid...

Adult Congenital Heart Disease In General Echocardiography Practice

Pediatric Echo Subcostal

The spectrum of adult congenital heart defects seen in echocardiography practice varies according to institutional practice and expertise. Half a century ago, survival with severe congenital heart disease was less common. Today, nearly 80 of such patients in industrialized societies now survive into adulthood. Most are followed up in centers that specialize in adult congenital heart diseases (CHDs), but it is not uncommon for such adults to be seen in general echocardiography practice. Congenital Heart Disease in Adults Compatible With Survival to Adulthood With No Prior Surgery or Intervention Superimposed acquired age-related heart disease, e.g., hypertension, coronary artery disease. Spectrum of Congenital Heart Disease Modified from Kisslo JA, Adams DB, Leech GJ. Essentials of Echocardiography Congenital Heart Disease. New York Ceiba-Geigy, 1988. Fig. 5. Morphological left and right ventricle. What defines right vs left ventricle are the morphological characteristics. On...

Thrombolytic Therapy in Acute Myocardial Infarction

The beneficial effect of thrombolytic therapy in the treatment of acute myocardial infarction (AMI) is now well established 13-15 . Use of thrombolytic agents has become a standard emergency treatment in such situations to the extent that globally, such drugs are administered to over 500,000 patients each year. It has been estimated that three times that number could potentially benefit from such therapy 5,16 . Although effective, these products achieve complete reperfusion in, on an average, only 50 of patients, and side effects can include risk of hemorrhage (in particular intracranial bleeding) as well as hypertension.

HRT and Risk of Cardiovascular Disease in Women With Diabetes

And ischemic heart disease (IHD), MI, and total number of deaths among a cohort of almost 20,000 Danish nurses aged 41 years and older (173). The data showed that current users of HRT smoked more, consumed more alcohol, had lower self-rated health, but were slimmer and had a lower prevalence of diabetes than never users. In current users without diabetes, HRT had no protective effect on IHD or MI compared with never users. However current users with diabetes had an increased risk of death, IHD and MI compared with never users with diabetes. These findings suggest that HRT does not protect women against IHD. Rather the effect of treatment is modified by diabetes, with an increased risk among women with diabetes using HRT.

Role of the reninangiotensin system in cardiovascular disease in diabetes

As reviewed elsewhere in this book, multiple factors, including hyperglycemia, insulin resistance, dyslipidemia, hypercoagulability, and inflammation contribute to the pathogenesis of atherosclerosis in DM. Although there is considerable evidence for a role of the RAS in vascular remodeling, inflammation, thrombosis, and atherogeneis (81-83), the role of this system in atherosclerosis in the context of the other diabetes-associated cardiovascular risk factors is not fully understood. There is a growing body of evidence from both clinical studies and experiments in diabetic rodent models suggesting that the RAS contributes to CVD in both type 1 and type 2 diabetes.

Polycystic Ovary Syndrome and Cardiovascular Risk

PCOS is associated with an increase in cardiovascular risk factors (189). In addition to obesity that is commonly present and independently associated with increased cardiovascular risk, women with PCOS have dyslipedemia, hypertension and elevated PAI-1 levels. Obesity is a prominent feature in women with PCOS as about half of the patients are obese. Also, obesity appears to confer an additive and synergistic effect on the mani Women with PCOS have higher serum triglycerides, total and LDL cholesterol and lower HDL cholesterol levels than weight-matched regularly menstruating women (190). These findings however, vary and depend on the weight, diet and ethnic background. In a large study of non-Hispanic white women, elevated LDL-C was the predominant lipid abnormality in women with PCOS (191). An additional parameter contributing to the elevated cardiovascular risk is hypertension. Obese women with PCOS have an increased incidence of hypertension and sustained hypertension is threefold...

Heart Disease

And force of the heart action, so it is given in special cases as a sedative (especially in heart disease). It was Dr William Withering (1741-1799), from Wellington, in Shropshire, who first introduced digitalin into general medical practice. He published an account of the Foxglove and some of its medical uses in 1788. It is said he got his information from a witch LILY-OF-THE-VALLEY provides a drug (convallotoxin) that has been used as a substitute for digitalin (Lloyd), which can act as a heart stimulant, thoiugh it is less powerful then digitalin. The root was used in Ireland for heart disease (Maloney), and it was widely prescribed in Russian folk medicine (Kourennoff). OLEANDER (Nerium oleander) has an active principle that operates in much the same way as digitalis, and is used in the treatment of heart conditions, particularly in Russia, where it is included in the official pharmacopeia (Thomson. 1976). Another plant with a digitalin-like action is the American shrub WAHOO...

Ischemic Stroke

Stroke remains one of the major causes of death and a leading cause of functional impairment, resulting in long-term disability. The latter is manifest by neurological dysfunction and significant reduction in the ability to perform activities of daily living. There are greater than 20 million incident strokes worldwide each year, resulting in more than 5.5 million annual deaths (World Health Report, 2002). Ischemic stroke is by far the most prevalent, accounting for about 88 of all strokes. Despite the advent of treatment using intravenous tissue-type plasminogen activator and the promise of additional acute therapies, effective pre- and post-stroke prevention are paramount for reducing the burden of stroke (Adams et al., 2005 Sacco et al., 1997). marked reduction in ischemic brain infarction and neuroprotection after cerebral ischemia in mice, with a direct correlation between the preservation of bioenergetic cellular status and the inhibition of activation of caspase cell-death...

How may selection bias affect trial findings

Exclusion of high-risk patients in clinical trials has other ramifications. Several post myocardial infarction studies that evaluated prophylactic beta-blocker therapy included patients with a broader spectrum of risk. Contrary to what one would expect, these trials showed that the benefits of beta-blockade were more pronounced in patients with complicated infarcts (and no contraindications to beta-blocker therapy) than in patients with uncomplicated infarcts.1 By excluding high-risk patients, beneficial effects may be missed. Selection bias may also increase the chances of finding favorable treatment effects. Study subjects typically have above-average education, as well as a personal interest in the research project. As a consequence, their level of adherence with the study medication is usually high. Additionally, since study subjects are usually free of other conditions and take few if any other medications (healthy volunteer effect), the likelihood of drug- drug interactions is...

What is the clinical relevance of composite outcomes

Combining events of similar severity such as cause-specific mortality, non-fatal myocardial infarction and stroke is generally accepted. In addition, the diagnostic criteria for these events are well defined and can be validated. Problems emerge when events of varying severity are combined. Adding self-reported angina, vascular procedures, and hospitalizations to major cardiovascular events is debatable. Whether a patient is hospitalized or has a costly procedure could be seen as a marker of disease severity, but it could also be influenced by whether the patient has health insurance coverage. Experience has shown that the more subjective and the least serious events that represent components of a composite outcome are the most likely to respond favorably to treatment, compared to events that are more objective and serious. In MIRACL, more than 3,000 patients with unstable angina or non-Q-wave acute myocardial infarctions were randomized to 80 mg of the lipid-lowering drug...

What if the component benefits differ

In LIFE,2 first-line treatment with the angiotensin receptor blocker losartan (Cozaar) was reported to be more effective than the beta-blocker atenolol (Tenor-min) in reducing the composite outcome -- cardiovascular mortality, stroke and acute myocardial infarction (see discussion about atenolol in Chapter 17). The major contributor to the modest 13 reduction in the composite outcome (p 0.02) was a 25 reduction in stroke risk (p 0.001). There was no significant decrease in the risk of cardiovascular (CV) mortality or myocardial infarction and, in fact, there were more infarctions in the losartan group. How should these findings be interpreted, regulated and promoted Would it be fair to conclude that losartan reduced the risk of CV mortality, stroke and myocardial infarction (with the latter trending in the wrong direction) A more rational conclusion would be to say that compared to atenolol, losartan reduced the risk of stroke, but only if the statistically significant stroke...

Whats the danger with subgroup analyses

As an example of post-hoc analyses, take the case of a placebo-controlled trial of a calcium channel blocker in patients with acute myocardial infarction.2 Although no overall mortality benefit from the active intervention was observed, a positive trend in the findings persuaded the investigators to perform subgroup analyses, which showed a significant reduction in mortality for infarction patients with normal myocardial function. The publication failed to report that mortality correspondingly increased in patients with impaired myocardial function, suggesting a negative inotropic drug effect. Additionally, this analytic exercise was not defined a priori. It should not be surprising that this post-hoc finding has yet to be confirmed in another calcium channel blocker trial. The ISIS-2 trial tested the effects of streptokinase and aspirin, individually and in combination, on short-term mortality in patients admitted with acute myocardial infarction. The trial demonstrated mortality...

Was the result for the primary outcome clearly stated in the conclusion and supported by the confidence interval

Connolly H, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997 337 581-8. 5. Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000 343 1826-32. 3. Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000 343 1826-32. 1. Hulley S, Grady D, Bush T, et al., Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in post-menopausal women. Heart and Estrogen progestin Replacement Study (HERS) Research Group. JAMA 1998 280 605-13. 3. Petitti DB. Hormone replacement therapy and heart disease prevention. Experimentation trumps observation. JAMA 1998 280 650-2. 1. Hulley S, Grady D, Bush T, et al., Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in post-menopausal women. Heart and Estrogen progestin Replacement Study (HERS) Research...

What are the challenges in attributing causation

If the universe of all possible adverse effects were known at the outset, data collection would be fairly straightforward. The challenge is capturing unanticipated adverse drug effects. After all, the general practitioner may not link his her sedative prescription to a patient's hip fracture12 and the urologist may overlook the association between the estrogen-treated patient with prostate cancer and his admission for an acute myocardial infarction or stroke. Many drugs have unexpected adverse effects that do not surface until years after their

What determines interchangeability for efficacy

Similar effects on a surrogate marker represents a very unreliable indicator that one drug may be safely substituted for another. The limitations of these markers are discussed in Chapter 19. The fact that all ACE inhibitors lower elevated systolic blood pressure does not mean that all ACE inhibitors are interchangeable. Antihypertensive treatment is most meaningful when it is documented to have actual health benefits, i.e., reduction in risk of fatal and non-fatal stroke, myocardial infarction and heart failure.

Does blood pressure lowering predict clinical benefit

Blood pressure lowering is one of the most well-known surrogate markers. It is well established that hypertension increases the risks of stroke, acute myocardial infarction and heart failure. A very large number of clinical trials of antihypertensive agents have documented that lowering blood pressure reduces the risk of these vascular complications. But can we conclude that the entire benefit of treatment is mediated through blood pressure lowering Or do antihypertensive agents have meaningful actions that are unrelated to blood pressure lowering Growing evidence indicates that the latter is the case, so the choice of antihypertensive may be important.

Can drug safety be a primary trial outcome

Of an offsetting increase in major vascular events. CLASS also reported a GI benefit, but only after redefining the study outcome post-hoc and excluding the data from the second 6 months of the one-year trial. The increase in major thrombotic events (mainly acute myocardial infarction) with the coxibs, a recognized class effect, was confirmed in 2004 in two placebo-controlled trials in patients with colon polyps.2'10 The manufacturer of rofecoxib decided on a voluntary recall of the drug from the market, whereas the manufacturer of celecoxib did not.

What went wrong

Ventricular extrasystoles on the electrocardiogram, serum cholesterol, and bone density serve as examples of surrogate endpoints. The presence of ventricular extrasystoles in coronary patients is associated with higher mortality and sudden death, elevated levels of serum cholesterol are related to the risk of acute myocardial infarction and premature death, and low bone density is linked to the risk of fractures. In principle, treatment that reduces the frequency of ventricular extrasystoles, reduces serum cholesterol, or increases bone density should reduce morbidity and mortality, if the links between the surrogates and outcome(s) are strong, and ifthe surrogate is in the causal pathway. Of course, trials using The widespread presumption that premature ventricular extrasystoles might cause sudden cardiac death served as the basis for the design of the Cardiac Arrhythmia Suppression Trial (CAST), sponsored by the National Heart, Lung, and Blood Institute. The primary objective of...

Contemporary Cardiology

Preventive Cardiology Insights Into the Prevention and Treatment of Cardiovascular Disease, Second Edition, edited by JoAnne Micale Foody, md, 2006 The Art and Science of Cardiac Physical Examination With Heart Sounds and Pulse Wave Forms on CD, by Narasimhan Ranganathan, md, Vahe Sivaciyan, md, and Franklin B. Saksena, md, 2006 Management, edited by David A. Morrow, md, 2006 Cardiovascular Disease in the Elderly, edited by Gary Gerstenblith, md, 2005 Platelet Function Assessment, Diagnosis, and Treatment, edited by Martin Quinn, mb bch bao, phd and Desmond Fitzgerald, md, frcpi, fesc, app, 2005 Diabetes and Cardiovascular Disease, Second Edition, edited by Michael T. Johnstone, md, cm, frcp(c) andAristidis Veves, md, dsc, 2005 md and Cam Patterson, md, 2005 Heart Disease Diagnosis and Therapy A Practical Approach, Second Edition, by M. Gabriel Khan, md, frcp(London), frcp(c), facp, facc, 2005 Cardiac Transplantation The Columbia University Medical Center New York-Presbyterian...

Preface to the First Edition

The cause of diabetes mellitus is metabolic in origin. However, its major clinical manifestations, which result in most of the morbidity and mortality, are a result of its vascular pathology. In fact, the American Heart Association has recently stated that, from the point of view of cardiovascular medicine, it may be appropriate to say, diabetes is a cardiovascular disease (1). But diabetic vascular disease is not limited to just the macrovasculature. Diabetes mellitus also affects the microcirculation with devastating results, including nephropathy, neuropathy, and retinopathy. Diabetic nephropathy is the leading cause of end-stage renal disease in the United States, while diabetic retinopathy is the leading cause of new-onset blindness in working-age Americans. The importance of this text on Diabetes and Cardiovascular Disease is evident by the magnitude of the population affected by diabetes mellitus. Over 10 million Americans have been diagnosed with diabetes mellitus, while...

Have We Made Progress

The explosion of health information and nutrition education programs has led to good progress on several fronts. Deaths from heart disease have declined and, to a slight degree, so have deaths from some cancers. On average, the intake of total fat and saturated fat has decreased. Food labeling provides much more useful information now. Restaurants offer more low-fat and low-calorie options on their menus. Nutritionists are now assessing our progress in meeting the goals of Healthy People 2010. These efforts will include evaluating healthful behaviors in the areas of fitness and nutrition, ensuring a safe food supply, and reducing and preventing diseases such as osteoporosis, cancer, diabetes, heart disease, and stroke.

Perioperative Cardiac Complications

Major cardiac complications presenting as myocardial infarction, myocardial ischemia, cardiac failure, or life-threatening dysrhythmias contribute significantly to perioperative morbidity and mortality. Preventive strategies are of major importance since even despite adequate treatment these events are associated with poor outcome. According to Poldermans and Boersma (2005), the incidence of a perioperative myocardial infarction is 0.185 in the United States. Approximately 50,000out of 27 million patients who are given anesthesia for surgical procedures annually suffer perioperative myocar-dial infarction. The cause is a prolonged mismatch between myocardial oxygen demand and supply owing to the stress of surgery or as the result of a sudden rupture of a vulnerable plaque followed by thrombus formation and coronary artery occlusion. of myocardial infarction by 56 (p 0.04), and the surrogate risk of cardiac death and nonfatal myocardial infarction by 67 (p 0.002). Administration of...

Vitamins and Minerals as Antioxidants

Every cell in our body needs oxygen to use the nutrients that food provides. However, when oxygen is used by cells, by-products called free radicals are formed. If allowed to accumulate, these free radicals can damage tissues, cells, and deoxyribonucleic acid (DNA, the genetic material of cells). The process of oxidative damage can be observed as the browning that occurs when sliced apples or potatoes are exposed to the air or the rancid flavor that butter and cooking oils develop when stored for long periods. Environmental pollutants such as cigarette smoke and ultraviolet light from the sun also contribute to the formation of free radicals in our bodies. Although not proved, studies suggest that excess free-radical production can increase the risk of cancer, heart disease, cataracts, and the other types of cell deterioration that are associated with aging.

Discharge And Home Healthcare Guidelines

Aortic valve insufficiency (AI) is the incomplete closure of the aortic valve leaflets, which allows blood to regurgitate backward from the aorta into the left ventricle. The retrograde blood flow occurs during ventricular diastole when ventricular pressure is low and aortic pressure is high. The backflow of blood into the ventricle decreases forward flow in the aorta and increases left ventricular volume and pressure. In compensation, the left ventricle dilates and hypertrophies to accommodate the increased blood volume. Eventually, the increase in left ventricular pressure is reflected backward into the left atrium and pulmonary circulation. Risk of premature death from AI, as well as complications and the chronic need for medication because of congenital heart disease, is approximately 50 . Dilation or distortion of the aortic root may be due to systemic hypertension, aortic dissection, syphilis, Marfan syndrome, and ankylosing spondylitis. Rheumatic heart disease and endocarditis...

Gender Ethnicracial And Life Span Considerations

AS can occur at any age, depending on the cause. Congenital stenosis is usually seen in patients younger than 30 years old. In patients between the ages of 30 and 70 years, the cause is equally attributed to congenital malformation and rheumatic heart disease. Among children born with AS, 75 are male, and overall approximately 80 with AS are male. Atherosclerosis and degenerative calcification of the aortic valve are the predominant causes for stenosis in people older than 70 years. Ethnicity and race have no known effect on the risk of AS.

Screening for fetal complications

The identification of fetal structural abnormalities allows the opportunity for in utero therapy, planning for delivery, for example, when the fetus has major congenital heart disease, parental preparation and the option of termination of pregnancy should a severe problem be diagnosed. Major structural anomalies are present in about 3 of fetuses screened at 20 weeks' gestation. Detection rates vary depending on the system examined, skill of the operator, timeallowed for thescan and quality of theultra-sound equipment. Follow-up data is important to audit the quality of the service. Women must appreciate the limitations of such scans. Local detection rates of various anomalies such as spina bifida, heart disease, facial clefting and the like should be made available. Written information should be given to women early in pregnancy explaining thenatureand purposeof such scans highlighting conditions that are not detected such as cerebral palsy and many genetic conditions. It is important...

Organization of a Pharmaceutical Company

Cific basic research areas that are technology platforms, such as genomics or protein chemistry or medicinal chemistry, biology or therapeutic focused, such as cardiovascular disease, or functional oriented (e.g., high-throughput screening or x-ray crystallography) (Fig. 1.24). Research role is the discovery and characterization of potential disease targets and possible molecules as interventions for the targets. Research needs to deliver product candidates to the development division for clinical work. Vertical organization based on drug categories often is done throughout a company from research, to development, and through marketing, forming cross-functional business units to optimize communication and coordination leading to drug development and product marketing in a specific therapeutic area.

Clinical Utility of Echocardiography

Echocardiography in Dyspnea, Ventricular Dysfunction, and Heart Failure Cardiac Murmurs and Valvular Heart Disease Infective Endocarditis Suggested Reading Cardiac ultrasonography has both practical and technical advantages over other cardiovascular imaging techniques (Table 2). Doppler echocardiography assessment of cardiovascular structure, function, and hemodynamics is a reliable noninvasive tool to localize and quantify the severity of cardiovascular disorders in a cost-effective and noninvasive manner.

Clinical Description

DCM is defined by the World Health Organization (WHO) as myocardial disorder ''characterized by dilatation and impaired contractility of the left ventricle or both left and right ventricles. It may be idiopathic, familial genetic, viral and or immune, alcoholic toxic, or associated with recognized cardiovascular disease in which the degree of myocardial dysfunction is not explained by the abnormal loading conditions or the extent of ischemic damage. The histological findings are frequently nonspecific. The usual presentation of the disease is heart failure, which is often progressive. Arrhythmias, thromboembo-lism, and sudden death are common and may occur at any stage.'' 1

Differential Diagnosis

FDCM is distinguished from other specific cardiac diseases and systemic processes resulting in secondary ventricular dilatation and dysfunction 1 eccentric hypertensive cardiomyopathy, ischemic cardiomyopathy, decompensated valvular heart disease, alcoholic cardio-myopathy, and myocarditis. Less common are cardiomyopathies resulting from amyloidosis, sarcoidosis, hemochromatosis and other metabolic disorders, and peripartum cardiomyopathy. Doxorubicin can cause toxic cardiomyopathy.

Macromolecular Composition

Since the first report of a link between C. pneumoniae and coronary heart disease (CHD) in 1988, 15 the chlamydia-arteriosclerosis theory has been challenged by a vast number of epidemiological and experimental studies, resulting, however, in contradictory outcomes. Recent meta-analysis of serological studies did not confirm the early reports of a serologic correlation. 16,17 But direct investigation of arteries by PCR and immunohistochem-istry revealed that 25 to 50 of atherosclerotic vessels contain chlamydiae compared to only 2 of healthy vessels. 17,18 There is, however, considerable variation among different studies and only poor correlation between the different detection methods. 17

Medical Circulatory Disorders Except AMI with Cardiac Catheter without Complex Diagnosis

Coronary artery disease (CAD) is the leading cause of death and illness in Western societies. A number of conditions result from CAD, including angina, congestive heart failure, and sudden cardiac death. CAD results when decreased blood flow through the coronary arteries causes inadequate delivery of oxygen and nutrients to the myocardium. The lumens of the coronary arteries become narrowed from either fatty fibrous plaques or calcium plaque deposits, thus reducing blood flow to the myocardium, which can lead to chest pain or even myocardial infarction (MI) and sudden cardiac death. Coronary Artery Disease Coronary Artery Disease (Arteriosclerosis) 249

Efficacy in Models of Ischemic Injury

APC has been shown to be effective in models of ischemic stroke in both the rabbit 131 and mouse 92,132 . Reduced ICAM-1 expression and reduced tissue CD11b were observed in the murine model, indicating the likelihood of reduced neutrophil extravasation 132 . Moreover, efficacy was demonstrated to be dependent on both EPCR and PAR-1 or PAR-3

The Mthfr Gene Product MTHFR

The MTHFR 677C T polymorphism has a relatively high frequency throughout the world. The 677TT genotype is present in about 12 of the general population and shows a heterogeneous distribution among ethnic groups with an allele frequency ranging from 0.045 in Sri Lanka to 0.3 in Caucasians and Americans (13). MTHFR 1298A C shows an allele frequency of 0.3 in Canadians, Austrians, and Dutch individuals (10,11,14). The allele frequency of MTHFR 1317T C is 0.05 in Canadian individuals (10) and 0.059 in a Turkish population (15) and was quite common in a small population of Africans (the allele frequency among nine healthy Africans was 0.39) (10). In the study of Meisel et al., none of 1000 healthy Caucasians and only 1 of 1000 coronary artery disease patients tested positive for MTHFR 1317T C (16). Some of the clinical implications of MTHFR 677C T are summarized in Chapter 2. The implications of MTHFR 677C T and MTHFR 1298A C in cardiovascular disease, cerebrovascular disease, venous...

Ultrasound screening for fetal anomalies

The detection of cardiac anomalies is of particular interest. Early prenatal detection of congenital heart disease (CHD) has increased due to advances in ultrasound resolution and the incorporation of at least a 4-chamber cardiac view in the routine anomaly scan, which is now accepted as standard in the UK. There is, however, regional variation in antenatal detection of CHD, with those obstetric centres close to cardiac units faring better than those situated in more remote areas. There also appears to be a discrepancy between countries, which reflect different obstetric practice for example, the policy of universal anomaly scanning between 20 and 22 weeks in the UK compared with targeted anomaly scanning in the USA.

Hypolipidemic 3thia Fatty Acids

High serum levels of triglyceride (TG)-rich lipoproteins, i.e. very low density lipoproteins (VLDL) and its remnants are important risk factors for coronary artery disease.1 Serum TGs can be lowered either by dietary treatment with fish oils or by pharmacological treatment with drugs of the fibrate class. Classically, the decrease in plasma TG concentrations upon fibrate treatment (Table 1) are thought to be the result of a decreased hepatic secretion of VLDL accompanied by an enhanced plasma TG clearance, possibly due to the induction of lipoprotein lipase (LPL) activity in peripheral tissues.2

Effects of sleep deprivation

Figure 3.5 Corticalplasticity is reflected by localchanges in SWA. In each panel regions with SWA increase are in red, while in blue are regions with SWA decrease. White circles indicate electrodes with significant SWA activity change. (a) Increased SWA after a rotation learning task. Six electrodes with significant differences from baseline located in the right sensorimotor area were found 3 . (b) Decreased SWA following left arm immobilization for one day was found in three electrodes in the right sensorimotor cortex 4 . (c) Increased SWA following rTMS of the left premotor cortex 5 . (d) Increased SWA at the right inferior frontalgyrus, symmetricalto Broca's area, in a stroke patient with expressive aphasia following 4 hours of speech therapy. See plate section for color version.

Immunophenotypic Analysis of Platelets

With an average diameter of 3 m, platelets are the smallest circulating cellular component in peripheral blood. The primary role of circulating platelets is to maintain hemo-stasis. The evaluation of platelets by flow cytometry has proven beneficial in the investigation of many disease states, including inherited defects such as Bernard-Soulier syndrome, Glanzmann thrombasthenia, and storage pool disease (Michelson et al., 2001). Flow cytometric techniques have been used in blood bank applications such as quality control of platelet concentrates, immunophenotyping of platelet surface receptor polymorphisms, platelet crossmatching, and detection of feto-maternal anti-platelet antibodies. Platelet hyporeactivity may result in potentially life-threatening bleeding including intracranial hemorrhage, while platelet hyperreactivity may result in intravascular thrombosis resulting in potentially life-threatening acute myocardial infarction or stroke. Consequently, antiplatelet therapies...

Background Information

In the absence of an exogenously added platelet agonist (see Basic Protocol 1), the activation state of circulating platelets in vivo, as judged by the binding of an activation-dependent monoclonal antibody or similar reagent, can be determined. Circulating activated platelets have been detected in patients with stable and unstable angina, acute myocardial infarction, acute cerebrovascular ischemia, peripheral arterial occlusive disease, diabetes mellitus, pre-eclampsia, hemodialysis, systemic inflammatory response syndrome, septic multiple organ dysfunction syndrome, myeloproliferative disorders, and Alzheimer disease. Platelet-derived microparticles are increased in acute coronary syndromes, cardiopulmonary bypass, transient ischemic attacks, and patients with prosthetic heart valves. Platelet hyporeactivity has been reported in very-low-birth-weight preterm neo-nates and may contribute to the propensity of intraventricular hemorrhage in that patient group.

Comparison of the In Vitro Sensitivity of Chlamydia pneumoniae to Macrolides and a New Benzoxazinorifamycin KRM1648

Question of persisistent infection after treatment is of potential importance because C. pneumoniae has been associated with chronic diseases, such as atherosclerosis and coronary heart disease in sero-epidemiological studies and by direct detection of C. pneumoniae in atheromatous lesions.

Lack of Autoimmunity After Innate Overactivation A Role for Interferons and the Nervous System

As discussed, autoimmune responses are induced similarly to an immune response against pathogens. Both involve an early phase of innate immune activation followed by the activation of adaptive T and B cell responses. It is noteworthy that innate immunity may be overactivated to a state resulting in suppression rather than priming of T cells. Interestingly, some clinically acute infections such as measles virus infection show a phenotype of early severe inflammatory disease and immunosuppression later. Measles patients frequently suffer from superinfectious bacterial pneumonia and often fail to react with a delayed type hypersensitivity (DTH) reaction to intradermal tuberculin protein, a classical type IV immune response according to Coombs 53 . In mice, measles virus leads to intense activation of macrophages and dendritic cells that finally results in an overactivated state associated with increased apoptosis and failure to prime T cell responses 54,55 . Consistently, an infection...

Genetic Considerations

HF is a complex disease combining the actions of several genes with environmental factors. Many HF risk factors have genetic causes or are associated with genetic predispositions. These include hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), coronary artery disease, myocardial infarction, and hypertension. Genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) and sympathetic system have also been associated with susceptibility to and or mitigation of HF. Gene variants in the alpha-2c adrenoceptor and the alpha-1 adrenoceptor have been associated with a higher risk of HF among African Americans.

Betablocking medication

Beta-blockers, unless contraindicated, are now standardised prescription in the UK and the USA following myocardial infarction (Brand, et al., 1995 Department of Health National Service Framework for Coronary Heart Disease, 2000). These guidelines recommend that patients be prescribed beta-blockers for at least 12 months following myocardial infarction. This means that most post-MI patients attending cardiac rehabilitation will require an exercise prescription that respects the effects of beta-blockade, including an altered cardio-respiratory response, changes in physical performance capability, slowed oxygen kinetics and potential side effects such as postural hypotension (Hughson and Smyth, 1983 Reents, 2000). The year 1979 appears to be a watershed for research published on the potential interactions between beta-blockade and perceived exertion. Three studies (Davies and Sargeant, 1979 Sjoberg, et al., 1979 van Herwarden, 1979) reported that the use of beta-blockade did not affect...

Current and future therapies

The limited success achieved with diet exercise coupled with the realization that obesity is a chronic disease requiring lifelong treatment has fueled the intense drive to develop an effective drug therapy. Unfortunately, this attempt has received a lot of negative press for a variety of reasons, ranging from the inappropriate use of thyroid hormone, diuretics, and addictive sympathomimetics to the withdrawal of fenfluramine dexfenfluramine owing to associated valvular heart disease and pulmonary hypertension (88,89). Although a few have questioned the wisdom of using pharmacologic agents to treat obesity (90), most health care professionals and experts in this field lament the lack of safe and effective drug(s) to complement lifestyle modifications (diet exercise). Despite the many challenges inherent in this enterprise, recent advances in the understanding of the mechanisms pathways that regulate modulate appetite and energy expenditure (albeit studied mostly in rodents) have...

Goals of Genetic Studies

Many of the promises of genetics investigations have probably been grossly overstated. The immediate potential of the ongoing and planned investigations into the genetics of cardiovascular disease is more promising for gene-directed therapy (the use of genetic information to guide the judicious use of medical interventions) than for somatic gene therapy (the use of a gene or gene product which, when introduced into a human organ, changes the function of the organ). The realistic promises of current genetics studies include the elucidation of disease mechanisms the identification of new targets for the development of therapeutic pharmacologic agents and the use of genetic markers to identify individuals for whom a particular agent is either effective or unusually hazardous. This approach, called pharmacogenomics, improves the safety and efficacy of treatments, and enhances the ability to preferentially select subjects for clinical trials based upon genetic predispostion and for...

Pigment Epithelium Derived Factor PEDF

PEDF also known as serpin F1 (SERPINF1), is a multifunctional secreted protein that has anti-angiogenic and neurotrophic functions. Found in vertebrates, this 50 kD protein holds promise in the treatment of such conditions as heart disease, cancer and choroidal neovascularization (Filleur et al., 2009). PEDF is secreted by many retinal cells including M ller cells, endothelial cells, pericytes, and pigment epithelium cells of retina (Doll et a ., 2003 Barnstable et al., 2004 Tombran-Tink et al., 2010). Studies conducted on PEDF depleted mice, showed that lack of this gene results in serious abnormalities in both, cell differentiation as well as in retinal morphology (Doll et. al., 2003). In 2003 the first hypothesis emerged that PEDF may hamper angiogenesis by direct reduction of VEGF gene expression (Yamagishi et al., 2003). Most recent data confirm also that PEDF has direct effect on vascular endothelial growth factor receptor 1 (VEGFR-1) by increasing g-secretase

Regulation Of The

Significantly decreased the creatine uptake rate but did not alter the CRT content (55- and 58-kDa bands). Creatine depletion from P-GPA supplementation increased creatine uptake capacity in the soleus and red gastrocnemius muscle, a change accompanied by 70-150 increases in CRT protein. However, the creatine uptake rate of white gastrocnemius muscle was unchanged, even though its CRT content increased by 230 , suggesting that total CRT content is unrelated to creatine uptake activity. It should be noted that unlike the previous study, this study determined the total rather than the plasma membrane content of the CRT. The relationship between creatine content and the levels of CRT remains unclear. In a human study, moderate supplementation with creatine increased creatine content of skeletal muscle without significant changes in levels of CRT protein or mRNA (Tarnopolsky et al., 2003). Disease states also affect the CRT content of skeletal and heart muscle. In humans, the CRT content...

Hair Tourniquet Syndrome

More common in infants younger than 6 mo, and the diagnosis is often delayed 3 to 4 d (28). The offending hair or thread is often concealed in natural skin wrinkles. A severely ischemic toe can be mistaken for an arterial embolism, which may arise in infants with congenital heart disease. Although complete necrosis of the toe is rare, a toe amputation has been required for some infants (29).

Macrovascular Disease And Diabetes An Overview

Both type 1 and type 2 diabetes are powerful and independent risk factors for coronary artery disease (CAD), stroke, and peripheral artery disease. More specifically, the Framingham study showed that type 2 diabetes is associated with approximately a twofold increase in CAD in men and a fourfold increase in women (41). It is also known that patients with diabetes have the same risk of acute myocardial infarction than patients without diabetes with a history of previous myocardial infarction, thus all patients with diabetes have to be considered in secondary prevention for CAD (42). Mortality from CAD in individuals with diabetes is also higher than in subjects without diabetes (43).

Effects of Estrogen on Inflammatory Markers

Recent studies have indicated that oral estrogen therapy may increase levels of CRP in healthy postmenopausal women suggesting that estrogen may initiate or aggravate inflammation (67,68). In contrast, animal studies failed to demonstrate such proinflammatory effects of estrogen when given by subcutaneous implantation or injection (69). In this regard, a recent study in postmenopausal women showed that oral but not transdermal estrogen therapy increased CRP by a first pass hepatic effect (70). Additionally, although oral HRT may increase CRP it reduces other inflammatory markers including E-selectin vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM)-1, and soluble thrombomodulin (71), indicating that the increase in CRP after oral HRT may be related to metabolic hepatic activation and not to an increased inflammatory response. However, because CRP is a predictor of adverse cardiovascular prognosis and may be involved in the process of atherosclerosis, the route...

What are the Cellular Effects of the Non Antioxidant Properties of the Tocopherols

The mechanism by which vitamin E produces cellular events could be in principle related to the known radical chain breaking properties of the molecule. This would imply that regulation of certain cellular functions is controlled by the production and elimination of lipid soluble free radicals and that vitamin E serves as a radical scavenger. The biological difficulty of controlling the propagation of radical chain reactions makes this mechanism improbable. Furthermore, if this were the mechanism of action of the tocopherols, other similar radical chain braking molecules, and in particular the eight natural tocopherol analogues, would act analogously this is however often not the case. Thus, it can be assumed that a-tocopherol modulates cellular behavior by specific interactions with enzymes, structural proteins, lipids and transcription factors. Similarly, troglitazone, an antidiabetic drug of the thiazolidinedione class, acts as an insulin sensitizer and improves hyperglycemia....

Nutrient Composition

A medium-sized raw carrot is an excellent source of beta-carotene, which is converted into vitamin A. Carrots are a relatively good source of fiber. In addition to beta-carotene, carrots contain two other carotenoids alpha-carotene and lutein. The carotenoids, which are responsible for the bright-orange color of carrots, have antioxidant properties and may help prevent cancer and heart disease. Lutein also has been looked at for its role in protecting the eye from free-radical damage and maintaining vision. Cooking carrots makes them more digestible and appears to increase the amount of vitamin A available for use in the body. However, the vitamin A content of fresh or frozen carrots is twice that of canned versions.

Primary Nursing Diagnosis

If the patient has developed endocarditis as a result of IV drug abuse, an addiction consultation is essential, with a possible referral to an appropriate treatment program. Surgical replacement of the infected valve is needed in those patients who have an infecting microorganism that does not respond to available antibiotic therapy and for patients who have developed infectious endocarditis in a prosthetic heart valve. (See Coronary Artery Disease, p. 248, for a full discussion of the collaborative and independent management of a patient following open heart surgery.)

Cardiac investigations in pregnancy

The amount of radiation received by the fetus during a maternal chest X-ray (CXR) is negligible and CXRs should never be withheld if clinically indicated in pregnancy. Transthoracic echocardiogram is the investigation of choice to exclude, confirm or monitor structural heart disease in pregnancy. Transoesophageal echocardiograms (TOE) are also safe with the usual precautions to avoid aspiration. Magnetic resonance imaging (MRI) and chest computerized tomography (CT) are safe in pregnancy. Routine investigation with electrophysiological studies and angiography are normally postponed until after pregnancy but angiography should not be withheld in, for example, acute coronary syndromes. General considerations in pregnant women with heart disease Cardiac events such as stroke, arrhythmia, pulmonary oedema and death complicating pregnancies in women with structural heart disease, are predicted by 6

The Nature Of Hypertension

Hypertension is a raised systemic arterial blood pressure (BP). However, BP is a continuously distributed variable and the numerical boundary between nor-motension and hypertension is arbitrary and is based on the increasing cardiovascular risk, in particular stroke, as BP rises (Fig. 1) 7 . A WHO-based classification of hypertension is shown in Table 1. Considering end-point trials of cardiovascular risk (more specifically, stroke), it is now widely accepted that maintaining BP below 140 90 mm Hg is beneficial and that a BP of 140 90 mm Hg is therefore considered abnormal 10 . However, the level at which pharmacological treatment is used differs between Europe and North America. In North America patients with a diastolic BP of 85 mm Hg or greater are more likely to be given drug treatment to lower BP, but in Europe the criterion for starting antihypertensive drug therapy is approximately 10 mm Hg higher. An isolated numerical definition of hypertension of 140 90 mm Hg or more fails...

Description Medical Cardiac Arrhythmias and

Junctional tissue may take over as the heart's pacemaker if the sinus node fails to produce an impulse or if that impulse is blocked in its conduction through the AV node. Junctional escape rhythms may be caused by digitalis toxicity, acute infections, oxygen deficiency, inferior wall myocardial infarction, or stimulation of the vagus nerve. If the junctional tissue becomes irritable or increasingly automatic, it may override the sinus node and pace at a faster rate. Nonparoxysmal junctional tachycardia is often the result of enhanced automaticity, usually called irritability, which can be the result of digitalis toxicity, damage to the AV junction after an inferior myocardial infarction or rheumatic fever, or excessive administration of catecholamines or caffeine. Paroxysmal junctional tachycardia (a rapid rhythm that starts and stops suddenly) is usually the result of a re-entry mechanism.

Sleeprelated breathing disorders

OSA is associated with considerable morbidity and mortality, particularly from hypertension, cardiovascular disease, and insulin resistance 16 . Furthermore, the excessive daytime sleepiness associated with OSA can result in decreased quality of life 18 and increased risk for automobile accidents 19 or serious industrial accidents 20 .

Clinical Significance Of Nucleoside Transporters

Nucleoside transporters themselves can serve as drug targets. As stated above, the endogenous nucleoside adenosine functions as a signaling molecule and regulates a number of physiological processes via binding to specific cell surface receptors.1'2 Nucleoside transporter-mediated cellular uptake represents a major mechanism for the termination of adenosine signaling. By enhancing local adenosine concentrations, ENT inhibitors can potentiate the adenosine effect and produce therapeutic benefits. Coronary vasodilators such as dipyridamole, dilazep, and draflazine are potent hENT1 inhibitors that can substantially increase and prolong the cardiovascular effects of adenosine.2 Dipyridamole is used clinically as a vasodilator, and draflazine has been shown to exert cardioprotective effect in humans.134 Adenosine is an endogenous neuroprotective agent. By binding to A1 and A2 receptors, adeno-sine decreases excitatory amino acid neurotransmission, inhibits inflammation, and promotes...

Pdl Pacher md phd and Csaba Szabo md phd

Macro- and microvascular disease are the most common causes of morbidity and mortality in patients with diabetes mellitus (DM). Diabetic vascular dysfunction is a major clinical problem, which underlies the development of various severe complications including retinopathy, nephropathy, neuropathy, and increase the risk of stroke, hypertension, and myocardial infarction (MI). Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, are closely associated with oxidative and nitrosative stress, which can trigger the development of cardiovascular disease. Recently, emerging experimental and clinical evidence indicates that high-circulating glucose in DM is able to induce oxidative and nitrosative stress in the cardiovascular system, with the concomitant activation of an abundant nuclear enzyme, poly(ADP-ribose) poly-merase-1 (PARP) . This process results in acute loss of the ability of the endothelium to generate nitric oxide (NO endothelial dysfunction) and also...

Oxidative and Nitrosative Stress in Diabetic Cardiomyopathy

The development of myocardial dysfunction independent of coronary artery disease in DM has been well documented, both in humans and experimental studies in animals (86-90). Diabetic cardiomyopathy is characterized by complex changes in the mechanical, biochemical, structural, and electrical properties of the heart, which may be responsible for the development of an early diastolic dysfunction and increased incidence of cardiac arrhythmias in diabetic patients. The mechanism of diastolic dysfunction remains unknown but it does not appear to be as a result of changes in blood pressure, microvascular complications, or elevated circulating glycated hemoglobin levels (86-90).

Leading Causes of Death

Figure 10.1 illustrates mortality patterns for non-Hispanic white females in the United States for the years 1999 and 2000. The top row of panels shows the age-specific death rate per 100,000 individuals on a log-log scale. The columns plot all causes of death, death by heart disease, and death by cancer. Figure 10.1 Age-specific mortality patterns by cause of death. Data averaged for the years 1999 and 2000 for non-Hispanic white females in the United States from statistics distributed by the National Center for Health Statistics, http nchs , Worktable Orig291. The top row of panels shows the age-specific death rate per 100,000 individuals on a log-log scale. The columns plot all causes of death, death by heart disease, and death by cancer. The second row of panels shows the same data, but plots the age-specific acceleration of death instead of the age-specific rate of death. Acceleration is the derivative (slope) of the rate curves in the top row. The bottom row takes...

Role Of Transthoracic Echocardiography

Transthoracic echocardiography (TTE) can be helpful in the management of AF by (1) identifying pathological conditions that may predispose to AF, and (2) identifying conditions that may increase the risk of thromboembolism (Table 1). For patients who present with their initial episode of AF, a search is usually made to determine the most likely associated systemic condition. The most common associated conditions include a history of systemic hypertension or coronary artery disease. Also to be considered are mitral valve disease (especially rheumatic mitral stenosis), pneumonia sepsis, clinical or subclinical thyrotoxicosis (especially in the elderly), pericarditis, pulmonary embolism, pharmaceuticals (e.g., aminophylline), and excess caffeine or alchohol ingestion (Table 2). Patients are often referred for a TTE to investigate for occult mitral stenosis, to assess the severity of mitral regurgitation (with consideration of mitral valve surgery if it is severe), for assessment of left...

Global Burden of Traffic Accidents

Currently, traffic accidents comprise the most common cause of traumatic deaths throughout the world and the most common cause of death and disability in the 15- to 44-yr-old age group in developed countries. In 2002, about 1.2 million people were killed in road traffic accidents, and by the year 2020, according to WHO data (1), this figure is projected to almost double, making traffic accidents the third (from the ninth) leading cause of death and disability worldwide (following ischemic heart disease and mental depression). Despite a large number of cars and accidents in high-income countries, however, the percentage of fatalities is low (Table 1). A good marker of the motorization progress in a particular country is the percentage of pedestrians among all victims of traffic accidents, e.g., high in the low-income countries and eastern Europe (due primarily to a lack of road infrastructure and the absence of a separation between pedestrian and car streams).

Polycystic ovary syndrome

Syndrome may be the presentation of a complex genetic trait disorder. The features of obesity, hyperinsulinaemia, and hyperandrogenaemia which are commonly seen in PCOS are also known to be factors which confer an increased risk of cardiovascular disease and non-insulin dependent diabetes mellitus (NIDDM) 6 . There are studies which indicate that women with PCOS have an increased risk for these diseases which pose long-term risks for health, and this evidence has prompted debate as to the need for screening women for PCOS 7 .

Important Issues To Be Addressed

Although we have achieved major accomplishments towards the development ofFTIs and GGTIs as therapeutic agents for cancer and cardiovascular diseases, there are several important issues that remain tobe addressed. We still do not know the precise mechanism by which these agents inhibit tumor growth. Although we have recently discovered the PI-3 kinase AKT-2 survival pathway as a target for FTI-induced apoptosis in human tumors, we still do not know which farnesylated protein upstream of PI3-kinase in this pathway is targeted by FTIs (81). The kinetics of inhibition of AKT-2 activity by FTI-277 are fast and suggest a farnesylated protein with a short half-life. Although RhoB has a short half-life, we have demonstrated that RhoB does not affect AKT-2 activity (81). Furthermore, we have shown that both farnesylated and geranylgeranylated RhoB suppress human tumor growth in nude mice arguing against RhoB being a target for FTIs (86). Downstream of AKT-2, we do know that phosphorylation of...

Natural History Of

With the progression of CAN and the development of sympathetic deficits and disabling symptoms such as orthostatic hypotension, a poor prognosis has been reported with up to a 60 5 year mortality (39). However, other studies have not predicted such a dire outlook, as 90 of asymptomatic subjects with reduced HRV without the presence of symptoms were still alive after 10 years (36). However, the presence of symptoms, (again in particular postural hypotension) was associated with reduced survival (73 alive after 10 years). The precise cause of death in these subjects is controversial most probably reflect coexistent renal and cardiovascular disease, but a small number of deaths remain unexplained and the potential causes are discussed (see Cardiac Denervation Syndrome).

Clinical manifestation

Cardiovascular findings usually the last lesions to be recognized peripheral pulses often severely diminished hypertension coronary artery disease causes angina pec-toris and subsequent myocardial infarction mitral valve prolapse gastrointestinal hemorrhage, usually gastric in origin less commonly, hemorrhaging occurs in urinary tract or cerebrovascular system

Epa And Dha Possess Different Metabolic Properties

It is generally accepted that high levels of plasma cholesterol represent an important risk factor for coronary artery disease. However, more resent research suggests that high serum levels of triglyceride (TG)-rich lipoproteins, i.e, very low density lipoprotein (VLDL) and its remnants are also important risk factors.1,2 Serum lipids can be lowered either by dietary treatment with fish oil3,4 or by pharmacological treatment with drugs of the fibrate class.5 Fibrate action has been partly ascribed to increased fatty acid oxidation, decreased TG synthesis and secretion, and enhanced clearance of VLDL from serum due to a down-regulation of hepatic apoC-III gene-expression.6,7

Manifestations of the Spectrum of Mps I Disease

The broad range of severity, both in overall disease status as well as in individual components of the disease, leads to a very heterogeneous population of patients in varying stages of disease progression within the various body systems. At the severe end of the disease spectrum, Hurler patients have severe developmental problems, whereas Hurler-Scheie patients show little or no mental retardation but may experience learning disabilities. Scheie patients do not lose intellectual function, in general. Hurler patients can experience cardiac failure due to stiffening of the heart as well as coronary artery disease. Their valvular disease does not progress fast enough in most cases to be the primary cardiac problem. In contrast, intermediate and milder patients have valvular disease problem as their dominant cardiac problem, often beginning at age 8 to 10, and continuing through their teenage years and

Stroke and Cerebrovascular Disease

Fecal incontinence is a common complication after stroke and affects about 30-40 of patients in the acute phase and 11 at 3 and 12 months 16-18 . The occurrence of bowel and urinary symptoms is related to the size of vascular lesion in particular, fecal incontinence is associated with the severity of the stroke 18 . Large ischemic frontoparietotemporal lesions can induce a higher incidence of urinary and bowel symptoms than can frontal injury alone. In the Copenhagen Stroke Study, patients with fecal incontinence in the first week after stroke were significantly more frequently women and more often had a history of former stroke comorbidity of other disabling diseases than patients without fecal incontinence 18 . The same study reported that lesions in patients with fecal incontinence were significantly more often due to a hemorrhage, were larger in size, and more often involved the cerebral cortex than those in patients without fecal incontinence. Patients with fecal incontinence...

Surgical Kidney Ureter and Major Bladder Procedures for Nonneopolycystic with CC

Complications include liver, pancreatic, spleen, and lung cysts aneurysms of the cerebral artery or abdominal aorta colonic diverticula and mitral valve prolapse. Approximately 40 of adult patients die of coronary or hypertensive heart disease. About 10 to 40 of people with ADPKD have berry aneurysms, and 9 die as a result of subarachnoid hemorrhages.

Quality of life and comorbidities in patients with restless legs syndrome

Several authors found that patients with RLS have impaired quality of life compared to the general population 1,88,89 or to patients with either cardiovascular disease or type 2 diabetes 90 primarily in the physical, but also some mental health domains (e.g. social functioning, role limitation due to emotional reasons). RLS also appears to be associated with unfavorable lifestyle behaviors, adverse effects on daytime functioning 91 , and a high incidence of psychosocial impairment 10,19,90 . Severe sleep deprivation might be responsible for diminished daytime functioning. However, the uncomfortable, often painful sensations render activities associated with sitting quietly (e.g. working on a computer, resting, watching a movie or play, long travel, etc.) extremely challenging. Consequently, patients with serious symptoms may be forced to alter their lifestyle and social life in order to avoid these situations. Recent studies indicate that RLS, in addition to significantly diminishing...

Molecular Genetics

Mutation detection strategies were initially complicated by the presence of two partial pseudogenes, ABCC6-C1 and ABCC6-C2, in the human genome. They are both products of large genomic duplications containing 5' portions of ABCC6 as well as part of the neighboring pM5 gene, located upstream of ABCC6. ABCC6-C1 contains the promoter region as well as the first nine exons of ABCC6, whereas ABCC6-C2 is nearly identical to the 5' untranslated region and exons 1-4. They are located in close proximity to ABCC6 on the short arm of chromosome 16. Both are highly homologous to their origin and differ only in a few nucleotide positions. 19 Current mutation detection methods employ gene-specific primers (Table 1) which allow detection of over 70 of mutations using denaturing high-performance liquid chromatography (dHPLC) through WAVE technology (TransgenomicTM) as a screening technique 20 and over 80 with direct sequencing of the entire ABCC6 coding region. Mutation detection has not only solved...

Mendelian and Complex Disorders

In contrast, complex disorders, such as cardiovascular disease, diabetes, cancers, and psychiatric disorders, are common in the general population. In these disorders, genetics plays a significant role, but the biology of the disease is due to a tangled web of genetic and environmental interactions. Consequently, complex disorders generally do not display the distinct inheritance patterns seen in Mendelian disorders.

Platelet Platelet Interactions

Increased platelet activation may lead to platelet aggregation and thrombosis. This can result in clinical syndromes such as myocardial infarction and stroke, both of which are major causes of morbidity and mortality. Reduced platelet-platelet interaction can result in bleeding problems, which although much rarer can also be serious.

Contraindications for Anaesthesia

There are only a few contraindications for anaesthesia in LRPE and EERPE. Absolute contraindications are elevated intracranial pressure or non-treatable disorders of coagulation. Advanced stages of heart failure, severe chronic obstructive pulmonary diseases, elevated intrapulmonary shunts and a ventriculoperito-neal shunt are relative contraindications 8-10 . Anaesthesia in these patients may require extended monitoring and postanaesthetic care. Surgery should be delayed for at least 6 weeks in patients with a recent myocardial infarction or a percutaneous coronary intervention with implantation of coronary stents, to avoid re-infarction or a deleterious stent thrombosis.

Nutritional Consequences Of Interesterification

Perhaps chemical interesterification's greatest advantage over hydrogenation lies in nutrition. At present, there are still unsettled nutritional concerns regarding trans fatty acids and their possible links to coronary heart disease 105-107 . Trans fatty acids are present in many edible fats and oils produced worldwide, yet these substances occur in great proportions in partially hydrogenated margarines. Barring non-hydrogenated margarines, literature data indicate that the typical trans fatty acid content of margarines is 10-27 in the United States and 10-50 in Canada 108,109 .

Apoptosis In Ischemic Injury

An important feature of ischemic injury is the accompanied regulation of apoptotic genes. These genes either participate in the execution of apoptosis or have a regulatory role. Expression of caspases, including caspases-2, -3, and -8 is induced following ischemia of the brain and kidneys in the rat (3739). In failing sheep hearts, ischemia is associated with gene expression of caspases -2 and -3 (40). Induction of Fas, Fas ligand, and the adapter protein FADD has also been documented following ischemia of the brain, heart, and kidneys (41-43). For ischemic liver, however, the tumor necrosis factor-a (TNF-a) system, rather than Fas, is upregulated (44). Another class of apoptotic genes that are induced by ischemia is the inhibitor of apoptosis protein (IAP). When cultured kidney cells are subjected to hypoxia to simulate ischemia, IAP2 is specifically upregulated (45). Upregulation of IAP2 results from hypoxic gene transcription, and yet can be dissociated from hypoxia-inducible...

Study Design Issues In Clinical Trials

The ultimate goal of a therapeutic intervention is to cure the disease. Given that a cure is not possible for essentially every neuromuscular and neurometabolic disorder, the goal is control of symptoms and functional improvement. Consequently, to determine the efficacy of a therapeutic intervention, the ultimate evidence of efficacy is an improvement in quality of life and functional capacity as well as a reduction in morbidity and mortality. An evaluation of the effect of an intervention on these clinical outcomes usually requires very large numbers of subjects followed for a long period of time to detect significant differences as is possible with common conditions such as cancer, heart disease and diabetes. Most of the neuromuscular and neurometabolic disorders are relatively rare and the recruitment of hundreds to thousands of patients is not feasible. Another issue is that of the cost of running such trials which can run into millions of dollars for clinical outcome evaluations....

Concluding Remarks

The association of apoptosis with ischemia reveals a new set of perspectives for treatment of ischemic diseases. Pharmacological inhibition of caspases has proven to be effective in diminishing ischemic damage in several experimental models. Promising results have also been achieved through genetic modulation of apoptotic genes, including Bcl-2. While critical evaluation and in-depth studies of these approaches are emerging, new strategies targeting other apoptotic events are expected. These, in combination with conventional methods, may lead to new therapies for ischemic diseases such as myocardial infarction, stroke, or ischemic failure of the liver and kidneys.

Homocysteine And Vascular Disease

Retrospective case-control studies have consistently suggested that total homocysteine is an independent risk factor for cardiovascular disease, with an increase in plasma tHcy of 5 mol L being associated with an increase in risk of approx 1.5-1.6 (9). Prospective studies have been less positive, but a recently updated meta-analysis confirmed that, overall, they were also supportive, suggesting an increment in risk of 1.20 (1.14, 1.25) for a 5- mol L increase in tHcy (10). However, Christen et al. (11) reviewed 43 studies and found that prospective studies showed a smaller or no association between tHcy and cardiovascular disease (CVD). Cleophas et al. (12) produced a pooled odds ratio (OR) of 1.49 (1.33-1.67) (where OR is the odds of coronary artery disease (CAD) in patients with elevated tHcy levels odds of CAD in patients with normal tHcy levels) in prospective cohort studies. However, they stated that the relevance of these results was minimized by significant heterogeneity in...

The Relationship Between Homocysteine And Folate

Plasma total homocysteine is strongly influenced by B-group vitamins, with folate status being the most important determinant of tHcy in the general population (3). Epidemiological studies cannot fully exclude the possibility that folate and vitamins B6 and B12 may have an association with cardiovascular risk and atherogenesis that is independent of tHcy levels. In fact, two recent studies have shown an association between low serum folate and CVD (25,26), whereas vitamin B6 has previously been shown to have an independent effect on CVD incidence (27). Folate supplementation, however, has been consistently shown to reduce tHcy, whether given as supplements or fortified foodstuffs (28,29), and more recently increased fruit and vegetable consumption has also been shown to modestly reduce tHcy (30). At least nine large randomized clinical trials of decreasing tHcy are currently in progress (9). These studies have sample sizes ranging from 2000 to 12,000 and are assessing a variety of end...

Genetic Factors Influencing Homocysteine

The relationship between folate and tHcy is strongly influenced by genetic factors, particularly the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene (37). The activity of MTHFR is crucial in determining the distribution between folate species used for homo-cysteine remethylation and DNA RNA synthesis. Individuals homozygous for the thermolabile variant of the gene (TT) comprise 10-15 of Caucasian populations and have reduced MTHFR activity and a significant elevation in tHcy if folate intake is low (36). This is associated with hypomethylation of DNA (37). However, they also have an increased intra-cellular methylenetetrahydrofolate pool and, hence, improved purine and pyrimidine syntheses, which may contribute to a protection against cancer in certain contexts (5). Epidemiological studies have failed to show a consistent relationship between the C677T polymorphism and CVD, although because many of these studies have failed to take folate status into...

Epilogue future clinical applications and limitations

There are a number of different potential sources of cells for tissue regeneration and repair. These include mature, somatic cells and adult stem cells, which may be obtained from the patient him herself, as well as the embryonic cells represented by hES cells and fetal germ cells. As somatic cells are committed to a particular cell lineage and commonly have a low proliferative potential, the orthodox view is that their ability to repair tissue will be low. And as the plasticity of adult stem cells is currently under dispute, theoretically hES cells may serve best as a source of any cell type for transplantation. For example hES cell-derived mesovascular progenitor cells have the characteristic of a high prolifer-ative activity (Protocol 7 and Figure 6), which may render them a good potential source of cells for building functional blood vessels, ex vivo and in vivo, for the treatment of ischaemia and cardiovascular disease.

Other hormonal changes

Both adrenal and ovarian androgen levels start to decline, from as early as 20 years of age through to the per-imenopause stabilizing by the time of the FMP. Some testosterone continues to be produced by ovarian theca cells. The drop in androgen levels is particularly profound in premature ovarian failure, spontaneous or iatrogenic. Oestrogen therapy can increase sex hormone binding globulin levels which leads to further falls in free androgen levels. The main postmenopausal oestrogen is oestrone which is produced mainly in peripheral adipose tissue and the postmenopausal ovary by aromatization of adrenal androstenedione. The somatotrophic axis becomes less active with ageing leading to insulin resistance and a rise in central adiposity. This in turn leads to the change in body shape from the female gynaecoid shape to the male android shape, itself an independent risk factor for coronary heart disease. There are a number of factors involved in perimenopausal weight gain including...

Therapeutic Applications

Marketed since 1960, streptokinase is one of the oldest and most cost-effective thrombolytic agents in routine clinical use. It is indicated for use by either the intravenous or intra-coronary route in the management of acute myocardial infarction, for the lysis of intracoronary thrombi, and for the improvement of ventricular function. Early administration of streptokinase is correlated with greater clinical benefit, the greatest benefit being evident when streptokinase is administered within the first 4 h of symptom onset. Streptokinase is also employed for the lysis of pulmonary emboli, acute arterial thrombi, and emboli, as well as the lysis of acute and extensive thrombi of the deep veins 51,54 . Along with urokinase, it is also utilized for degrading fibrin clots in arteriovenous catheters, including clots in external arteriovenous shunts of patients on hemodialysis. Varidase (Wyeth) is another commercial preparation containing streptokinase, and is indicated for use in treating...

Cardiovascular Safety Pharmacology

The definitive cardiovascular safety pharmacology study is the conscious telemetrized dog or non-human primate model. If profiling in the first and second tier screening assays does not identify cardiovascular risk, compounds can be advanced directly into a definitive GLP telemetry study in support of regulatory filing. For a compound or class of compound that do not have a sufficiently large window between hERG and other cardiovascular ion channels and target IC50 margins, they should be profiled in exploratory in vivo ambulatory radiot-elemetry implanted animals to assess the potential to prolong the QT interval and other cardiovascular parameters. The doses and concentrations used in this in vivo study should reflect 3x, 10x, and 30x of the projected efficacious therapeutic Cmax. Depending on the indication, compounds that do not significantly alter cardiovascular parameters in telemeterized animals, at 10x projected efficacious therapeutic Cmax may be progressed into further...

Clinical Significance

As noted above insulin resistance is an acknowledged cardiovascular risk factor. Thus, several large longitudinal studies of cardiovascular risk factors indicate that patients with insulin resistance are at increased risk for myocardial infarction. In fact, some authors have attributed the lower than predicted benefit of blood pressure lowering on myocardial infarction risk to the adverse metabolic effects of thiazides, including insulin resistance. Since most patients treated with thiazides are hypertensive, the potential added risk of insulin resistance (and hyperlipidemia, see below) should be taken into account when prescribing antihypertensive agents. If thiazides are used to treat hypertension, the relative risks and benefits must be carefully considered and very low doses (e.g., hydrochlorothiazide 6.25-12.5 mg day) should be tried first in an effort to reduce the risk of the developing insulin resistance. Also careful attention to maintaining a normal serum potassium...

Lipoprotein Glycation Oxidation and Glyco Oxidation

It has been postulated that enhanced glycation, oxidation, and glyco-oxidation of lipoproteins may underlie the development of macrovascular disease in diabetes. This is quite an attractive hypothesis because it would explain the individual variation in the development of complications in diabetes. Regardless of the similarity in glycemic control and cardiovascular risk factors, the development of complications would also depend on differences in oxidative stress and variations in the antioxidant defenses and in differences in the immune response to the modified lipoproteins. A short summary of the large body of evidence showing that modified lipoproteins may be relevant to the accelerated development of atherosclerosis in diabetes is presented next.

Hypertrophy of the Heart Invariably Leads to Failure

We have already explained how coronary artery disease can lead to failure by causing infarction (cell death) of part of the ventricular muscle when a coronary artery becomes occluded. Because cardiac muscle does not regenerate, such a lesion will be permanent. Another common source of heart failure is ventricular overload. Like any muscle, the heart tries to adapt to an increased workload by hypertrophy of its individual muscle fibers. Although such an adaptation is usually successful in skeletal muscle, it can lead to disaster in the heart.

Known sex hormone effects on vessel walls 41 General concepts

Sex hormones have gender-specific effects on cardiovascular risk factors such as lipid metabolism, obesity (central weight gain, i.e. android) and glucose metabolism possibly explaining the differences in cardiovascular disease (CVD) risk between men and women (Carani et al. 1997 Fonseca 2009 Liu et al. 2002 Vitale et al. 2010). All of these risk factors, along with blood pressure, are also risk factors of retinopathy and as such are another link between sex hormones and the development and progression of retinopathy (Cunha-Vaz 2011).

The Body Tries To Defend the Heart and the Brain

Ischemia will occur if blood pressure falls below 50 mm Hg and at even higher pressures if coronary artery disease is present. If the hypotension is severe, myocardial ischemia can depress the heart, which will further lower the blood pressure. Once this positive feedback situation begins, the circulation can collapse suddenly. Injury to other organs can be more insidious. Reduced blood flow to the renal cortex for more than a day can result in death of cortical tissue and renal failure. Furthermore, an increase in pulmonary capillary permeability often results in adult respiratory syndrome (ARDS), characterized by poor oxygenation of the blood and reduced pulmonary compliance. ARDS currently accounts for most of the late deaths in otherwise successfully resuscitated patients.

Specific Forms of Shock

In its most severe form, heart failure can cause cardiogenic shock. When the cardiac output becomes too low, ischemia in the periphery occurs which begins the downward spiral associated with the shock state. What makes cardiogenic shock so difficult to treat is that often the primary lesion itself is often irreparable, as in myocardial infarction or end-stage heart failure. Cardiogenic shock can also result from the abrupt appearance of a valve lesion or filling of the pericardial space with fluid that constricts the heart and opposes diastolic filling (pericardial tamponade). Fluid resuscitation will obviously be less effective in cardiogenic shock, although further elevation of preload may still improve cardiac output in selected patients. A Swan-Ganz catheter is often used to make sure that only enough fluid is added to achieve an optimal ventricular filling pressure.

Lipoprotein Oxidation and Glyco Oxidation

Several clinical studies further strengthened the morphological findings described above. Regnstrom and associates (167) have shown that the degree of susceptibility to oxidation of LDL isolated from 35 male survivors of MI was positively correlated with the severity of coronary atherosclerosis. Several other investigators described increased oxidizability of LDL in patients with coronary heart disease (168), and patients with carotid or femoral atherosclerosis (169).

Suggested Readings

Clinical aspects of heart failure, in Braunwald E, Ed., Heart disease a textbook of cardiovascular medicine. Philadelphia Saunders, 1992. Smith TW, Braunwald E, Kelly RA. The management of heart failure, in Braunwald E, Ed., Heart disease a textbook of cardiovascular medicine. Philadelphia Saunders, 1992. Weil M, von Planta EC, Rackow. Acute circulatory failure, in Braunwald E, Ed., Heart disease a textbook of cardiovascular medicine. Philadelphia Saunders, 1992.

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