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).

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.

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).

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.

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...

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.

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...

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.

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...

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.

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.

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

Aging, Heart Disease and Its Management Facts and Controversies, edited by Niloo M. Edwards, md, Mathew S. Maurer, md, and Rachel B. Wellner, md, 2003 Murmurs on CD, Second Edition, by Jules Constant, md, 2003 Primary Angioplasty in Acute Myocardial Infarction, edited by James E. Tcheng, md, 2002 B. Berger, md, Alexander Battler, md, and David R. Holmes, Jr., md, 2002 Management of Cardiac Arrhythmias, edited by Leonard I. Ganz, md, 2002 Diabetes and Cardiovascular Disease, edited by Michael T. Johnstone and Aristidis Veves, md, dsc, 2001 Interpretation, by Thomas M. Blake, md, 1999 Platelet Glycoprotein IIb IIIa Inhibitors in Cardiovascular Disease, edited by A. Michael Lincoff, md, and Eric J. Topol, md, 1999 Minimally Invasive Cardiac Surgery, edited by Mehmet C. Oz, md and Daniel J. Goldstein, md, 1999 Management of Acute Coronary Syndromes, edited by Christopher P. Cannon, md, 1999

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.

The Power of the Food Guide Pyramid

The Food Guide Pyramid was developed by the U.S. Department ofAgriculture. The pyramid incorporates many principles that emphasize a plant-based diet that is low in fat, high in fiber, and rich in important vitamins, minerals, and other nutrients. All of these factors contribute to optimal health and help you to control your weight and to reduce the risk of heart disease and some types of cancer. The arrangement of the food groups in a pyramid shape calls attention to the kinds of foods to eat more of and those to eat in moderation.

Definition Of Cardiac Rehabilitation

There are many aspects to the management of coronary heart disease (CHD), including pharmacological treatment, cardiac investigations, secondary prevention and revascularisation. Secondary prevention consists of a number of activities or measures that may be taken by patients with established disease, in order to reduce their risk of a further event (Lockhart, et al., 2000). Cardiac rehabilitation (CR) is acknowledged not only as integral in the management of patients with CHD, but also as the primary vehicle in delivering secondary prevention. Many definitions of CR exist, for example the World Health Organisation classifies CR as 'The sum of activities required to influence favourably the underlying cause of the disease, as well as to ensure the patient the best possible physical, mental and social conditions, so that they may, by their own efforts, preserve or resume when lost, as normal a place as possible in the life of the community' (World Health Organisation, 1993).

With Subcortical Infarcts And Leukoencephalopathy

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is associated with mutations in the NOTCH 3 protein, which maps to chromosome 19q12. NOTCH signaling is important in development, but in adults, NOTCH 3 expression is limited to vascular smooth muscle cells, where its function is unknown. Pathologically, there are granular deposits in small cerebral arteries producing ischemic stroke because of vessel wall thickening, fibrosis, and occlusion. These deposits are found in small arteries throughout the body, and diagnosis may be confirmed by the presence of the osmiophilic granules in the basement membrane of vascular smooth muscle cells on skin biopsies.

The Genetic Architecture of Quantitative Traits

Identifying genetic risk factors for cardiovascular disease might be facilitated by studying the genetic architecture of cholesterol metabolism or blood pressure rather that the presence or absence of cardiovascular disease itself. Cholesterol metabolism is an example of an intermediate trait or endophenotype for cardiovascular disease. That is, it is related to the disease and may be useful as a proxy measure of the disease.

The Metabolic Syndrome in HIVinfected Individuals

A constellation of laboratory and physical abnormalities, termed the metabolic syndrome, is associated with increased risk of cardiovascular morbidity and mortality (Table 2). This syndrome is seen in 24 of the US population overall its prevalence is increasing in the US. The metabolic syndrome encompasses disturbances in glucose, insulin, and lipid metabolism, associated with abdominal obesity. The presence of the metabolic syndrome roughly doubles cardiovascular disease mortality. In other studies, the risk for cardiovascular disease with metabolic syndrome is even higher. 14 by IDF criteria. Despite this low overall number, many patients in this study (49 ) had at least two features of the metabolic syndrome but were not classified as having the metabolic syndrome, typically because waist circumference was not in the metabolic syndrome range. The metabolic syndrome was more common in those individuals currently receiving protease inhibitors. Although the formally defined metabolic...

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...

Deep Vein Thrombosis and Pulmonary Embolism 321

To reveal an increased risk for thromboembolism, the examiner should pay special attention to the following conditions in the patient's medical history deep venous thrombosis, thrombophlebitis, pulmonary embolism, myocardial infarction, angina pectoris, other signs of coronary disease, cardiac arrhythmias, occlusion of arterial vessels, embolic events, strokes, pro

The Bottom Line on Fats

Dietary fat is a source of energy, but high-fat diets, especially diets high in saturated fat, increase the risk of gaining excessive amounts of weight and of developing diabetes, coronary artery disease, high blood pressure, and several types of cancer. This increased risk is the reason that health experts encourage us to reduce our intake of total and saturated fats by

Life Span and the Aging Process

This increase was likely due to several factors, but perhaps the most important was the improvement of sanitation, hygiene, and public health from 1900 to 1998. These improvements included purification of drinking water, treatment of wastewater, widespread vaccination, and improved access to health care. However, even as these sanitary measures were adopted, other elements of modern life emerged as strong influences on life span, such as diet, exercise, and socioeconomic status. Studies have shown that individuals who exercise regularly, eat a diet lower in saturated fats, and avoid unnecessary risk-taking live longer. This may be because such a lifestyle reduces the risk of developing cardiovascular disease and cancer, the top causes of death in developed countries.

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

Teach the patient factors that may precipitate anginal episodes and the appropriate measures to control episodes. Teach the patient the modifiable cardiovascular risk factors and ways to reduce them. Manage risk factors, including hypertension, diabetes mellitus, obesity, and hyperlipidemia.

Supplements Foods or Functional Foods

May protect against coronary artery disease, abnormal blood clotting, cancer May protect against coronary artery disease, macular degeneration, and cancer May protect against colon cancer, coronary artery disease May protect against cancer, coronary artery disease, diabetes May help prevent coronary artery disease and breast cancer

Ageing stress and the brain

Ageing of the brain is an important factor in overall ageing and mortality, and new insights have clarified the relationship between neuroregulation and ageing. First, neuronal loss in normal ageing is now known to be a minor change. Loss of synapses through dystrophic neuronal change is the hallmark of normal ageing. Second, similar dystrophic changes occur in the brain with chronic stress. In both instances, forebrain sites experience loss of synaptic input from brainstem regulatory nuclei. Third, functional ageing is attributed in part to lifetime stress, under the concept of 'allostatic load'. Being inseparable from the functions of appraising and responding to stress, the brain is an ultimate mediator of stress-related mortality, through hormonal changes that lead to proximate pathologies like hypertension, glucose intolerance, cardiovascular disease and immunological impairment. In chronic stress the brain shows clear allostatic compensations that lead to pathology....

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...

Diabetes And Circulatory Problems

People with diabetes, especially those with type 2 diabetes, are two to five times more likely to have problems with circulation to the heart, the legs, and the head when compared to individuals without diabetes. This is because diabetes predisposes a person to a condition called atherosclerosis. If you imagine a blood vessel as a water or drainage pipe, then atherosclerosis is buildup in the pipe narrowing the channel and impairing the flow. In the case of the blood vessel the buildup, called plaque, consists of a core of inflammatory cells, cholesterol, and lipids with a fibrous cap of smooth muscle cells (see Figure 3-1). The plaque can narrow the blood vessel, impairing blood flow. Occasionally the fibrous cap can rupture, and when this happens a blood clot forms, causing an acute blockage of the blood vessel. If the acute blockage happens in one of the blood vessels to the heart, it results in a heart attack. If it occurs in one of the blood vessels supplying brain tissue, it...

Content Of Cardiac Rehabilitation

Cardiac rehabilitation is a multifaceted intervention offering education, exercise and psychological support for patients with coronary heart disease and their families and involves a variety of specialist health professionals (Bethell, et al., 2001). Cardiac rehabilitation can promote recovery, enable patients to achieve and maintain better health, and reduce the risk of death in people who have heart disease (National Health Service Centre for Reviews and Dissemination, 1998). The challenge of CR, along with all the other aspects of secondary prevention, is the prevention of subsequent cardiovascular events, while maintaining adequate physical functioning and independence and a good quality of life (Giannuzzi, et al., 2003). Cardiac rehabilitation is a relatively new element in the care of the coronary patient in the UK, first being adopted around the late 1980s (Fearnside, et al., 1999). Cardiac rehabilitation is now embedded as an essential component in the management of heart...

Central Nervous System Cerebrovascular Accidents

Faecal incontinence may affect up to 40 of subjects immediately following a stroke, with a frequency of up to 15 of those who survive 3 years. It is associated with a higher mortality and greater likelihood of need for long-term (institutional) care (exceeding dementia as a reason for requesting nursing home placement). In the immediate poststroke period, incontinence has been shown to be associated with female gender, a history of previous stroke, and comorbidity of other disabling diseases, especially diabetes mellitus and hypertension. The cerebral lesions in those with incontinence are significantly more often a haemorrhage, larger in size, and more often involved the cerebral cortex than those without faecal incontinence 26 . The pathophysiology of urinary incontinence following a stroke has been categorised into three main mechanisms disruption of neuromicturition pathways, stroke-related cognitive and language deficits and concurrent neuropathy and medication use. Presumably,...

Goals Of Clinical Trials

To compare the efficacy of the test drug to that of the active competitor in terms of the composite endpoint of the prevention of death, nonfatal stroke, nonfatal systemic embolic events, and nonfatal myocardial infarction in patients with arterial fibrillation (AF). The efficacy endpoints in Example 3.2.7 are the occurrence of prespecified events. For the primary objectives, these events include all strokes and systemic embolic events while the secondary efficacy endpoints consist of death, nonfatal stroke, nonfatal systemic embolic events, and nonfatal myocardial infarction. As a result, the primary and secondary efficacy endpoints contain some overlapping events such as nonfatal strokes. The first tertiary objective is to evaluate the performance of the test drug on the prespecified subgroup based on the primary efficacy endpoint for the patients with a poor outcome. On the other hand, the second tertiary objective is to detect a possible interaction between the age (equal to 75...

Phase I cardiac rehabilitation

Phase I, which in most cases is the initial stage of the patient's cardiac rehabilitation pathway, is considered as the in-patient stage, or after a 'step change' in the patient's cardiac condition. These step changes include myocardial infarction, onset of angina, any emergency hospital admission for coronary heart disease, cardiac surgery or angioplasty and or stent, and first diagnosis of heart failure (SIGN, 2002).

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.

Phase III cardiac rehabilitation

The structure of phase III is usually at least two supervised exercise sessions per week, lasting over a period of between 6 and 12 weeks. One session of education per week may be offered. Physical training is often the key component of phase III CR, but psycho-social counselling and education regarding risk factors and lifestyle are important. Strategies to enable a reduction in depression, anxiety and uncertainty, accepting the heart disease and learning to cope with it are discussed as appropriate. As with earlier phases of CR, the involvement of family and significant others continues to be important. Risk stratification prior to patients commencing phase III exercise classes is essential and will be examined in Chapter 2.

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.

Acute Rheumatic Fever Introduction

Acute rheumatic fever is an autoimmune disease responsible for cardiac valve disease or rheumatic heart disease. It is associated with infections caused by the group A streptococcus and occurs about 2 to 6 weeks following a streptococcal upper respiratory infection. It is prevented by adequate treatment of the infection with appropriate antibiotic therapy within 9 days of onset of streptococcal infection before further complications can occur. Because rheumatic heart disease does not occur after only one attack and children are susceptible to recurrent attacks of rheumatic fever, it is vital that an initial episode is diagnosed and treated, and that long-term prophylactic therapy (5 years or more) is given following the acute phase. There is no specific test for rheumatic fever the diagnosis is based upon the manifestations using the revised Jones criteria as a guideline. Jones criteria consist of major manifestations (polyarthritis, carditis, chorea, subcutaneous nodules, and...

Approach To Risk Stratification

Risk stratification can be considered as the crux of assessment prior to entry into CR, but this approach should form part of a process of sound clinical reasoning. The reader will find reference to commonly used coronary heart disease (CHD) risk-stratification guidelines for supervised exercise. These guidelines are produced by authoritative organisations well respected in this field - American Heart Association (AHA, 2001), SIGN (2002) and the American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR, 2004).

Therapeutical Approaches for HCM Are Symptom Oriented

Septal myectomy can abolish the gradient caused by severe outflow tract obstruction. Alcohol septal ablation initiates controlled septal myocardial infarction to reduce the gradient. Dual-chamber pacing allows substantial reduction of the gradient and more aggressive medical treatment. Patients at high risk for SCD with important outflow tract gradient benefit from biventricular pacing properties of an implantable cardioverter defibrillator.

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

Inflammation Following Cerebral Ischemia

Reperfusion of ischemic parenchyma activates pro-inflammatory effectors, thereby exacerbating cerebral injury. As demonstrated in both animals and humans, inflammation leads to the release of proteases and free radicals by infiltrating neutrophils and increased leukocyte adhesion leading to capillary plugging, both of which are deleterious and expand the zone of irreversible injury ( Bednar et al. 1991, 1997 Dawson et al. 1996 del Zoppo et al. 1991 Dirnagl et al. 1999 Matsuo et al. 1994 Shimakura et al. 2000 Small et al. 1999 Sughrue and Connolly 2004 Yano et al. 2003). A major component of the inflammatory response involves the complement cascade. Complement is deposited on apoptotic neurons following cerebral ischemia (Cowell et al. 2003a Huang et al. 1999 Schafer et al. 2000). While the majority of systemic complement is produced hepatically, extrahepatic cells are also capable of manufacturing complement proteins (Morgan and Gasque 1996, 1997). Although the origin of neuronal...

Implementation Of Randomization

Note that the randomization procedure described above is probably the most frequently employed procedure for conducting clinical trials in the pharmaceutical industry with sample sizes smaller than a few thousands. For most clinical trials sponsored by the NIH or other cooperative groups, the sample size can be quite large. For example, the ISIS-2 (1988) study randomized 17,187 patients with suspected acute myocardial infarction to four treatment groups and 22,071 male physicians were enrolled to receive one of the four treatments in the U.S. Physician's Health Study (1989). An even larger study is the GUSTO (1993) study which enrolled a total of 41,021 patients with evolving myocardial infarction. As a result, it may not be feasible to adopt the randomization procedure described above. As an alternative, a centralized randomization center may be established for random assignment of treatments either by mail or by telephone. If the time between the screening and request for random...

Generalization Of Controlled Randomized Trials

In early 1970s, a high cholesterol level was known to be a risk factor for developing coronary heart disease. To confirm this, a trial known as the Lipids Research Clinics Coronary Primary Prevention Trials (CPPT) was initiated by the National Heart, Lung, and Blood Institute to test the hypothesis whether lowering cholesterol can prevent the development of coronary heart disease. In the CPPT trial, a total of 4000 healthy, middle-age males were randomized to receive either the cholesterol-lowering agent cholestyramine or its matching placebo (Lipids Research Clinics Program, 1984). The primary endpoint was the incidence of coronary heart disease after a seven-year follow-up. A statistically significant reduction of 1.7 in 7-year incidence of coronary heart diseases was observed for the cholestyramine group as compared to the placebo (8.1 versus 9.8 ). An expert panel recommended to extrapolate the results for the treatment of high cholesterol in populations that had never been...

Abnormalities of the V Wave

Shown is a jugular pulse tracing from a patient with severe constrictive pericarditis. Note the double descent with a dominant Y descent and relatively small X' descent. K indicates a pericardial knock sound. (From E. Craige, Heart Sounds. In E. Braunwald ed. , Heart Disease 2nd ed. . Philadelphia Saunders, 1984). Severe constrictive pericarditis. Shown is a jugular pulse tracing from a patient with severe constrictive pericarditis. Note the double descent with a dominant Y descent and relatively small X' descent. K indicates a pericardial knock sound. (From E. Craige, Heart Sounds. In E. Braunwald ed. , Heart Disease 2nd ed. . Philadelphia Saunders, 1984).

Gastrointestinal disorders

This poorly understood inflammatory condition is primarily a condition of preterm infants and those with congenital heart disease. It presents as an acute abdomen in the days or weeks after birth and varies in severity from mild to fatal. Diagnosis is clinical, aided by characteristic X-ray changes such as air in the bowel wall or biliary tree. Treatment is conservative with cessation of enteral feeding and with antibiotics or surgery.

Primary Nursing Diagnosis

The treatment needs to be initiated rapidly, within 6 hours of the onset of symptoms. Medical management for patients with CVAs typically includes support of vital functions and ongoing surveillance to identify early neurological changes as the patient's condition evolves. Although the hallmark of stroke is the abrupt onset of neurological symptoms and deficits due to the interruption of the vascular supply to a specific brain region, therapeutic intervention may save tissue that is at risk for infarction. Recombinant tissue-plasminogen activator (rt-PA) can improve outcome for some patients with acute nonhemorrhagic ischemic stroke if it is given within 3 hours of the onset of symptoms.

Creating a Professional Will

Nless a therapist is invulnerable and immortal, it is a good idea to prepare a professional will. One focus of this book is the therapist as human. Part of our humanity is our mortality and our vulnerability. Unpleasant as it is to think about, all of us are vulnerable to the unexpected. At any time a drunk driver, a stroke, a mugging, a heart attack, a fire, a plane crash, and countless other misfortunes may bring our life to a sudden and unexpected end. It is an ethic of both personal and professional responsibility to take our mortality and vulnerability into account in our planning.

Previous Medical History And Comorbidity

Limitation of functional capacity will often be attributable not to coronary heart disease but to co-morbid conditions. This may mean that functional capacity assessed by means of walking is both ineffective and inappropriate. Can we, therefore, effectively prescribe exercise to accommodate this diversity, and can we implement outcomes to measure the effectiveness of our interventions

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

Group Sequential Designs

Patients with reduced left ventricular function after myocardial infarction (MI) are at risk of congestive heart failure (CHF) and life-threatening ventricular arrhythmia. Moss et al. (2002) reported the results of the Multicenter Automatic Defibrillator Implantation Trial II that was designed to evaluate the potential survival benefit of a prophylactically implanted defibrilla-tor (in the absence of electrophysiological testing to induce arrhythmia) in patients with a prior myocardial infarction and a left ventricular ejection faction of 0.30 or less. Over a period of 4 years, a total of 1,232 patients were randomized in a 3 2 ratio to receive an implanted defibrillator (742 patients) or conventional medical therapy (490 patients). The defibrillator was implanted using the standard technique. Every effort was made to achieve defibrillation within a 10-J safety margin. The primary endpoint was all causes death. This trial employed a triangular sequential design (Whitehead, 1997) that...

Rosiglitazone And Pioglitazone

They usually take a few days to work, so you should not expect glucose levels to fall for at least a week or two. The medicine does depend on having enough insulin to be effective. In addition to their glucose-lowering effect, thiazolidinediones lower triglycerides and free fatty acid levels and raise total cholesterol, LDL cholesterol, and HDL cholesterol. Pioglitazone, when compared to rosiglitazone, is more effective in lowering triglycerides and raising HDL cholesterol. It also does not raise LDL cholesterol as much as rosiglitazone does. Since lipid abnormalities are associated with heart disease, it has been proposed that the lipid changes seen with these drugs (especially pioglitazone) might be beneficial. In small research studies these drugs have been shown to prevent the reblockage of coronary arteries after they have been opened with a procedure called coronary angioplasty. These medicines also seem to help fatty liver, an important abnormality found in many people with...

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...

Steps Towards Clinical Translation

Has found C3a receptor antagonism protects mice from transient, but not permanent cerebral ischemia. Although transient and permanent MCA occlusion resulted in similar degrees of endothelial ICAM-a expression and granulocyte infiltration into post-ichemic cortex, C3aR antagonism markedly diminished this phenomenon only in cases involving reperfusion. These findings suggest that translational efforts to bring anti-complement therapies to the bedside in patients suffering acute ischemic stroke should concentrate on administration in the setting of known reperfusion, for example following proven recanalization with IV TPA or endovascular methods. Along these lines, clinical studies regarding anti-inflammatory stroke therapies have been discouraging thus far. For example, the Enlimomab (anti-ICAM-1) antibody Acute Stroke Trial was halted following enrollment of 625 patients, as Enlimomab treated patients demonstrated worse outcomes than placebo treated patients (Furuya et al. 2001)....

Type 2 diabetes and igt

Type 2 diabetes in the United States is increasing at an alarming rate it is predicted that as many as 10 of the country's population will have diabetes by the year 2025 (83). Individuals with type 2 diabetes pass through a stage of IGT prior to diabetes onset (Fig. 1) (84,85). Depending on the criteria used for the diagnosis of IGT, 30-40 million Americans now have IGT, with 20 or more of the elderly being affected (86). This compares with the 16 million individuals who now have type 2 diabetes. As the average lifespan of Americans continues to increase, the frequency of progression of IGT to type 2 diabetes will also probably increase. IGT has two major associated problems increased cardiovascular disease and the progression to type 2 diabetes. The risk of cardiovascular disease with IGT is not as great as that seen in overt type 2 diabetes, but it is clearly greater than in age-matched controls (87). Progression to type 2 diabetes increases if individuals with IGT decrease their...

Outcomes in Diabetic Patients

Meta-analyses of ACE inhibitor trials provide compelling evidence that ACE inhibitors reduce cardiovascular events and mortality related to acute myocardial infarction (MI) and heart failure (90,91). Because diabetes is an independent risk factor for CVD (92) and the RAS and diabetes appear to interact at multiple levels, it is possible that diabetes may affect the efficacy of ACE inhibition on CVD. Several recent reports have provided retrospective analyses of data from diabetic subgroups, which participated in large ACE inhibitor trials. Although some of these trials were not designed to specifically address the effects of ACE inhibition in diabetes, comparison of the relative effects of ACE inhibition in the diabetic and nondiabetic subgroups may provide important insight into the role of the RAS in CVD in diabetes.

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.

Dysmetabolic Metabolic Syndrome Syndrome X

The obesity in the abdomen tends to be deep or visceral adiposity, which is associated with accelerated atherosclerosis and coronary artery disease (104). The presence of visceral fat in this syndrome is an example of the fact that not all forms of obesity are functionally the same and that different forms can pose different health risks. Patients with fat distributed in subcutaneous regions around the gluteofemoral areas and upper abdomen are at much less risk for complications such as hypertension, lipid abnormalities, and insulin resistance than those with visceral fat (124,125). The idea that adipose tissue releases important metabolites has been fueled by recent findings showing that fat may not be just a storage compartment but rather an active source for production of proteins central to obesity, insulin resistance, and lipid disorders. Adipose tissue has been demonstrated to produce leptin (126), resistin (127,128), and Acrp 30 AdipoQ (129-132), which have been proposed to...

Description Medical Diabetes

Long-term complications such as disease of the large and small blood vessels lead to cardiovascular disease (coronary artery disease, peripheral vascular disease, hypertension), retinopa-thy, and renal failure. Diabetic patients also have nerve damage (neuropathy) that can affect the peripheral nerves, resulting in numbness and pain of the hands or feet.

An Echo Shifting Approach for T2Weighted DSCMRI

Onstrated in the assessment of acute stroke patients and provided information on perfusion parameters from the entire brain (Fig. 7.3) (Flacke et al. 2000). Although the method is promising, a comparison of obtained rCBV and rCBF needs to be validated against a conventional EPI technique.

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

Heart Rate As A Measure Practicalities of measuring heart rate

Personal HR monitors, with a wireless chest-strap electrode transmitter and wristwatch receiver (e.g. Polar, Cardiosport brands), has made a simple, inexpensive and accurate measuring of HR possible. These devices, however, rely on a normal sinus rhythm. If there are disturbances to the normal ECG (e.g. atrial fibrillations or ectopic beats), the monitor will not be able to adjust for these. The next stage up from this is the use of more costly and sophisticated 3-to-12-lead ECG telemetry. For some patients who have undergone coronary bypass surgery, surgical sternal sutures sometimes interfere with the electrodes on the chest strap, and prevent it picking up a valid ECG signal.

Neuroplasticity and sleep

Changes in sleep activity, and particularly in local slow-wave activity (SWA) during NREM sleep, are highly sensitive markers of plastic changes in the cortex. For example, it was found that a brief ( 1 hour), simple motor learning task induced an increase in the SWA of the involved parietal cortex 140 (Figure 3.5a) conversely, immobilization of the non-dominant (left) arm led to a decrease in SWA at the corresponding cortical region 139 (Figure 3.5b). Local increases in SWA were also found in healthy subjects following high-frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS), a paradigm known to induce potentiation 138 (Figure 3.5c), while in stroke patients with expressive (Broca's area) aphasia a 4-hour program of speech therapy produced focal increases in SWA in the perile-sional area (Figure 3.5d). Additional findings from other EEG studies, showing local increases in SWA or sleep spindle activity that were significantly correlated with performance improvement in...

Patents and the Rise of Biotechnology Companies

In the same year, the Food and Drug Administration (FDA) approved Genentech's drug tPA (tissue plasminogen activator). This is a human blood protein that helps to dissolve fibrin, the major protein involved in forming blood clots at the site of an injury. After the healing process is complete and clotting is no longer required at the site of the injury, the body normally releases tPA to activate an enzyme called plasmin, which dissolves fibrin. However, it was discovered that tPA could also be used as a powerful drug in the treatment of certain heart attacks. Sometimes a blood clot forms spontaneously in the body. If the clot forms or lodges in the coronary arteries of the heart, the clot blocks blood flow to the heart muscle, resulting in what is commonly called a heart attack. If tPA is given to such patients within four hours of onset, the recovery is truly remarkable. Such patients are able to leave the hospital the next day with little or no after effects of the heart attack. A...

Impaired glucose tolerance is a disease

The prediabetes state of IGT is associated not only with progression to diabetes but also with increased coronary artery disease mortality therefore, it should be recognized, diagnosed, and treated early (see ref. 1 and Chapter 5 of this book). Moreover, the demonstration that lifestyle intervention can substantially prevent or delay the progression of IGT to type 2 diabetes underscores the need for early diagnosis (1). The accelerated heart disease in IGT probably stems from the presence of insulin resistance and its associated metabolic syndrome, which are defined in Table 2 according to the NCEP ATP III report (1). Three of five elevated factors, which are easy to measure, constitute the metabolic syndrome. Certain components of the syndrome, such as low HDL, elevated triglycerides, and hypertension, are well-known risk factors for cardiovascular disease. Other components that are less commonly measured in the clinical setting, such as elevated small, dense LDL cholesterol (the...

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.

Insulin resistance is a state of inflammation

In addition to the fact that components of the metabolic syndrome contribute to cardiovascular disease, increasing data suggests insulin resistance is a proinflammatory state in itself. Adipose tissue secretes substances (adipokines) that decrease insulin-mediated glucose uptake and or promote vascular inflammation (Table 3). Adipocytokines circulate at higher levels in obese animals or in humans with increased viceral adiposity. Tumor necrosis factor-a (TNF-a) directly suppresses activation of tyrosine kinase on the insulin receptor, resulting in insulin resistance (22). TNF-a levels are not only high in atherosclerotic vessels, promoting inflammation, but are elevated in damaged myocardium and have been implicated in heart failure (23). Adiponectin (Acrp 30) also arises from fat but, in contrast to TNF-a, is low in the circulation of obese humans and animals, enhances insulin-mediated glucose uptake, and inhibits inflammatory responses (24). Leptin is another substance from fat...

Nongenomic Actions Extranuclear Actions

The TH-related compound demonstrated with low metabolic activity and low affinity for nuclear thyroid hormone receptors, DITPA was able to increase cardiac contractility and peripheral circulation without significant effects on heart rate as well as improve hemodynamic performance in animal models of congestive heart failure after myocardial infarction 105 . Preliminary studies have been performed in patients with heart failure demonstrating a significant improvement in systolic cardiac index and systemic vascular resistance 106 . Future studies are needed with this and similar compounds to clarify if such drugs may represent a novel class of drugs for the treatment of heart failure.

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...

Consequences of fetal growth disorder

Of structurally normal fetuses is also associated with abruption and pre-eclampsia. Both these outcomes are associated with IUGR. Poor growth is also associated with perinatal death due to prematurity. It has been shown that growth restriction in early pregnancy is associated with an increased risk of spontaneous preterm birth. Labour appears to be initiated by the activation of the fetal hypothalamo-pituitary adrenal axis. In sheep, the effector hormone from the adrenal is cortisol, whereas in primates and - it is assumed - in the human, it is likely to be androgenic precursors of oestrogen. The effect in both species is stimulation of labour. Therefore, spontaneous preterm delivery may be a physiologically indicated response to a poor environment. Poor growth is also directly related to prematurity in the context of elective delivery for suspected fetal compromise. Poor fetal growth is also associated with increased morbidity and mortality in infancy. For example, the risk of sudden...

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.

Predisposing factors for anaphylaxis

Other factors that may predispose to severe disease are the use of medications that may interfere with the normal physiological response to an allergen, i.e. the epinephrine (formerly adrenaline) response. The typical drugs implicated are the cardiac drugs called angiotensin converting enzyme (ACE) inhibitors which inhibit the physiological angiotensin reaction to hypertension, and the more familiar beta blockers prescribed for ischaemic heart disease. The latter may inhibit the generation of a faster heartbeat to maintain organ profusion in the face of allergen-mediated fall in blood pressure.

Biology and Atherosclerosis

Decrease in VCAM-1 expression (49), potentially consistent with some in vitro work and again indicative of possible issues with in vitro vs in vivo findings. Regardless, the decrease in atherosclerosis is fairly consistent and in keeping with early surrogate marker studies in humans. For example, the PPAR-y agonists in clinical use have been shown to lower levels of circulating MMP9 (50,51), replicating the responses seen in vitro with VSMCs (38) and macrophages (37). PPAR-y agonists also decrease circulating levels of C-reactive protein (CRP) and levels of CD40 ligand (CD40L), both suggestive of an antiinflammatory effect (50). Several PPAR-y agonists have been found to decrease carotid intimal-medial thickness, a parameter linked with cardiovascular risk (52,53). These studies have all bolstered ongoing clinical trials examining the impact of PPAR ligands on cardiovascular endpoints. Independent of these direct effects on atherosclerosis, it remains possible that PPAR-y agonists...

Peroxisome Proliferator Activated Receptora in Vascular Biology Inflammation and Atherosclerosis

The clinical trials using fibrates could be considered in some sense tests of the cardiovascular effects of PPAR-a agonists. In the Veterans Affairs HDL Intervention Trial, patients with a prior history of cardiovascular disease and a relatively average LDL, low HDL, and only modestly elevated triglycerides experienced fewer recurrent cardiac events in response to the fibrate gemfibrozil as compared to placebo (23). It remains both

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...

Diabetes and vascular disease

From Contemporary Cardiology Diabetes and Cardiovascular Disease, Second Edition Edited by M. T. Johnstone and A. Veves Humana Press Inc., Totowa, NJ this chapter. In addition to coronary artery disease (CAD), patients with type 2 diabetes have a high prevalence and rapid progression of peripheral arterial disease (PAD), cerebral vascular disease, and complications of percutaneous coronary intervention including restenosis (6). The previously conventional view that high-grade occlusive, stenotic coronary lesions represent the final step in a continuum that begins with fatty streaks and culminates in high-grade stenosis has given way to a different paradigm because of evidence that thrombotic occlusion is frequently the result of repetitive rupture of minimally stenotic plaques. Thus, as many as two-thirds of lesions responsible for acute coronary syndromes (ACS) are minimally obstructive (less than 50 stenotic) at a time immediately before plaque rupture (9,10). Multiple episodes of...

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...

Antiplatelet therapy and diabetes

People with type 2 diabetes have a high incidence of overt cardiovascular and particularly CAD (1,2,5). Thus, it appears likely that subclinical atherosclerosis is often present even in entirely asymptomatic subjects. Accordingly, many physicians believe the treatment guidelines such as those promulgated by the Adult Treatment Panel of the National Cholesterol Education Program (69) for subjects with known overt CAD should be applied to all people with type 2 diabetes, even those without signs or symptoms of cardiovascular disease (CVD). Based on this rationale, prophylaxis with daily aspirin is appropriate for all people with type 2 diabetes who have no specific contraindications (see Therapeutic Implications).

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

In Vivo Applications Liver Transduction

The potential of liver-directed, HDAd-mediated gene therapy was investigated for the phenotypic correction of hypercholesterolemia in the apolipoprotein E-deficient mouse model. 6 Apolipoprotein E, a 34-kDa plasma glycoprotein, is a component of all plasma lipoproteins except low-density lipoprotein (LDL) and plays a major role in lipoprotein catabolism by acting as a ligand for the LDL-receptor (LDLR) and the LDLR-related protein for transport of excess cholesterol from the peripheral tissues to the liver for excretion. The apoE_ _ mouse is an excellent model for cardiovascular disease because they develop severe hypercholesterolemia and atherosclerotic lesions similar to those found in humans. Chan and coworkers investigated correction of hypercholesterolemia in apoE_ _ mice with either a FGAd or a HDAd expressing apoE. 6 Injection of apoE_ _ mice with FGAd resulted in an immediate rise in plasma apoE levels and a concomitant drop in plasma cholesterol levels to within normal range....

Effects of growth hormone and insulinlike growth factor 1 deficiency on ageing and longevity

Approved (Butterfield et al 1997) and non-approved administration of GH to ageing people, at 'so-called' rejuvenation clinics. These medical acts were reinforced by reports that GH deficiency increases the risk for cardiovascular disease (Rosen et al 1993) and leads to premature mortality (Rosen & Bengtsson 1990).

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