Universitatea Ovidius Constana Facultatea de Medicin Murean Ana-Maria MG I, gr.

10, seria B

HEART DISEASES

Bibliography: http://en.wikipedia.org/wiki/Heart_diseases

HEART DISEASES

Heart disease or cardiopathy is an umbrella term for a variety of different diseases affecting the heart. As of 2007, it is the leading cause of death in the United States, England, Canada and Wales killing one person every 34 seconds in the United States alone. Types of heart diseases: Coronary heart disease, Cardiomyopathy, Cardiovascular disease, Ischaemic heart disease, Heart failure Hypertensive heart disease, Inflammatory heart disease, Valvular heart disease.

Coronary heart disease

Coronary heart disease refers to the failure of the coronary circulation to supply adequate circulation to cardiac muscle and surrounding tissue. Coronary heart disease is most commonly equated with Coronary artery disease although coronary heart disease can be due to other causes, such as coronary vasospasm. Coronary artery disease is a disease of the artery caused by the accumulation of atheromatous plaques within the walls of the arteries that supply the myocardium. Angina pectoris (chest pain) and myocardial infarction (heart attack) are symptoms of and conditions caused by coronary heart disease.Over 459,000 Americans die of coronary heart disease every year. In the United Kingdom, 101,000.

Cardiomyopathy
Cardiomyopathy literally means "heart muscle disease" (Myo= muscle, pathy= disease) It is the deterioration of the function of the myocardium (i.e., the actual heart muscle) for any reason. People with cardiomyopathy are often at risk of arrhythmia and/or sudden cardiac death.

Extrinsic cardiomyopathies cardiomyopathies where the primary pathology is outside the myocardium itself. Most cardiomyopathies are extrinsic, because by far the most common cause of a cardiomyopathy is ischemia. The World Health Organization calls these specific cardiomyopathies.

Congenital heart disease

A congenital heart defect (CHD) is a defect in the structure of the heart and great vessels of a newborn. Most heart defects either obstruct blood flow in the heart or vessels near it or cause blood to flow through the heart in an abnormal pattern, although other defects affecting heart rhythm (such as long QT syndrome) can also occur. Heart defects are among the most common birth defects and are the leading cause of birth defect-related deaths. Symptoms and signs are related to the type and severity of the heart defect. Some children have no signs while others may exhibit shortness of breath, cyanosis, chest pain, syncope, sweating, heart murmur, respiratory infections, underdeveloping of limbs and muscles, poor feeding, or poor growth, build up of blood and fluid in lungs, feet, ankles and legs. Congenital heart defects cause abnormal heart structure resulting in production of certain sounds called heart murmur. Doctors can sometimes detect it with stethescope. However, all heart murmurs are not caused by congenital heart defects. CHD symptoms frequently present early in life, but it's possible for some CHDs to go undetected throughout life. The cause may be due to a genetic predisposition or an environmental exposure during pregnancy.Known genetic causes of heart disease includes chromosomal abnormalities such as trisomies 21, 13, and 18, as well as a range of newly recognised genetic point mutations, point deletions and other genetic abnormalities as seen in syndromes such as Velo-Cardio-Facial Syndrome, familial ASD with heart block, Alagille syndrome, Noonan syndrome, and many more. Known antenatal environmental factors include maternal infections (Rubella), drugs (alcohol, hydantoin, lithium and thalidomide) and maternal illness (diabetes mellitus, phenylketonuria, and systemic lupus erythematosus). Classification: Hypoplasia can affect the heart, which typically results in the failure of either the right ventricle or the left ventricle to develop adequately, leaving only one side of the heart capable of pumping blood to the body and lungs. Hypoplasia of the heart is rare but is the most serious form of CHD; it is called hypoplastic left heart syndrome when it affects the left side of the heart and hypoplastic right heart syndrome when it affects the right side of the heart. In both conditions, the presence of a patent ductus arteriosus (and, when hypoplasia affects the right side of the heart, a patent foramen ovale) is vital to the infant's ability to survive until emergency heart surgery can be performed, since without these pathways blood cannot circulate to the body (or lungs, depending on which side of the heart is defective). Hypoplasia of the heart is generally a cyanotic heart defect. Obstruction defects occur when heart valves, arteries, or veins are abnormally narrow or blocked. Common obstruction defects include pulmonary valve stenosis, aortic valve stenosis, and coarctation of the aorta, with other types such as bicuspid aortic valve stenosis and subaortic stenosis being comparatively rare. Any narrowing or blockage can cause heart enlargement or hypertension.

The septum is a wall of tissue which separates the left heart from the right heart. It is comparatively common for defects to exist in the interatrial septum or the interventricular septum, allowing blood to flow from the left side of the heart to the right, reducing the heart's efficiency. Ventricular septal defects are collectively the most common type of CHD, although approximately 30% of adults have a type of atrial septal defect called probe patent foramen ovale. Septal defects may or may not cause cyanosis depending on the severity of the defect. Cyanotic heart defects are called such because they result in cyanosis, a bluish-grey discoloration of the skin due to a lack of oxygen in the body. Such defects include persistent truncus arteriosus, total anomalous pulmonary venous connection, tetralogy of Fallot, transposition of the great vessels, and tricuspid atresia. Defects : Aortic stenosis Atrial septal defect (ASD) Atrioventricular septal defect (AVSD) Brugada syndrome Cardiomyopathy Dextrocardia DiGeorge's Syndrome Double inlet left ventricle (DILV) Double outlet right ventricle (DORV) Ebstein's anomaly Hypoplastic left heart syndrome (HLHS) Hypoplastic right heart syndrome (HRHS) levo-Transposition of the great arteries (l-TGA) Patent ductus arteriosus (PDA) Pulmonary atresia Pulmonary stenosis tetralogy of Fallot (ToF) pentralogy of Chantrall dextro-Transposition of the great arteries (d-TGA) Tricuspid atresia Truncus arteriosus Ventricular septal defect (VSD) Bicuspid aortic valve Mitral stenosis Shone's syndrome/ Shone's complex / Shone's anomaly Scimitar syndrome (SS) This is an incomplete list, which may never be able to satisfy certain standards for completion. You can help by expanding it with reliably sourced additions. Coarctation of the aorta (CoA) Interrupted aortic arch (IAA) Sometimes CHD improves with no treatment necessary. At other times the defect is so small and does not require any treatment. Most of the time CHD is serious and requires surgery and/or medications. Medications include diuretics, which aid the baby in eliminating water, salts, and digoxin and in strengthening the contraction of the heart. This

slows the heartbeat and removes some fluid from tissues. Some defects require surgical procedures to repair as much as possible to restore circulation back to normal. In some cases, multiple surgeries are needed to be performed to help balance the circulation. Interventional cardiology now offers patients minimally invasive alternatives to surgery. Device closures can now be treated with a standard transcatheter procedure using a closure device mounted on a balloon catheter.

Nutritional diseases Ischemic (or non-ischaemic) cardiomyopathy Commonly used term "ischemic
cardiomyopathy," referring to myocardial ischemia and infarction, is not supported by current cardiomyopathies classification schemes. Ischemic cardiomyopathy is a weakness in the muscle of the heart due to inadequate oxygen delivery to the myocardium with coronary artery disease being the most common cause. Anemia and sleep apnea are relatively common conditions that can contribute to ischemic myocardium and hyperthyroidism can cause a 'relative' ischemia secondary to high output heart failure. Individuals with ischemic cardiomyopathy typically have a history of myocardial infarction (heart attack), although longstanding ischemia can cause enough damage to the myocardium to precipitate a clinically significant cardiomyopathy even in the absence of myocardial infarction. In a typical presentation, the area of the heart affected by a myocardial infarction will initially become necrotic as it dies, and will then be replaced by myocardial scarring (fibrosis). This fibrotic tissue is akinetic; it is no longer muscle and cannot contribute to the heart's function as a pump. If the akinetic region of the heart is substantial enough, the affected side of the heart (i.e. the left or right side) will go into failure, and this failure is the functional result of an ischemic cardiomyopathy. In some individuals, severe emotional stress may lead to "takotsubo cardiomyopathy", a specific cardiomyopathy which has a particular aetiology Intrinsic cardiomyopathies: An intrinsic cardiomyopathy is defined as weakness in the muscle of the heart that is not due to an identifiable external cause. This definition was used to categorize previously idiopathic cardiomyopathies although specific external causes have since been identified for many. For example, alcoholism has been identified as a cause for some forms of dilated cardiomyopathy. To make a diagnosis of an intrinsic cardiomyopathy, significant coronary artery disease should be ruled out (amongst other things). The term intrinsic cardiomyopathy does not describe the specific etiology of weakened heart muscle. The intrinsic cardiomyopathies consist of a variety of disease states, each with their own causes. Many intrinsic cardiomyopathies now have identifiable external causes including drug and alcohol toxicity, certain infections (including Hepatitis C), and various genetic and idiopathic (i.e., unknown) causes. Intrinsic cardiomyopathies are generally classified into four types,[2][7] but additional types are also recognized: Dilated cardiomyopathy (DCM), the most common form, and one of the leading indications for heart transplantation. In DCM the heart (especially the left ventricle) is enlarged and the pumping function is diminished. Approximately 40% of cases are familial, but the genetics are poorly understood compared with HCM. In some cases it

manifests as peripartum cardiomyopathy, and in other cases it may be associated with alcoholism. Hypertrophic cardiomyopathy (HCM or HOCM), a genetic disorder caused by various mutations in genes encoding sarcomeric proteins. In HCM the heart muscle is thickened, which can obstruct blood flow and prevent the heart from functioning properly. Arrhythmogenic right ventricular cardiomyopathy (ARVC) arises from an electrical disturbance of the heart in which heart muscle is replaced by fibrous scar tissue. The right ventricle is generally most affected. Restrictive cardiomyopathy (RCM) is an uncommon cardiomyopathy. The walls of the ventricles are stiff, but may not be thickened, and resist the normal filling of the heart with blood. A rare form of restrictive cardiomyopathy is the obliterative cardiomyopathy, seen in the hypereosinophilic syndrome. In this type of cardiomyopathy, the myocardium in the apices of the left and right ventricles becomes thickened and fibrotic, causing a decrease in the volumes of the ventricles and a type of restrictive cardiomyopathy. Noncompaction cardiomyopathy has been recognized as a separate type since the 1980s. The term refers to a cardiomyopathy where the left ventricle wall has failed to grow properly from birth and has a spongy appearance when viewed during an echocardiogram. Symptoms and signs may mimic those of almost any form of heart disease. Chest pain is common. Mild myocarditis or cardiomyopathy is frequently asymptomatic; severe cases are associated with heart failure, arrhythmias, and systemic embolization. Manifestations of the underlying disease (e.g., Chagas' disease) may be prominent. Most patients with biopsy-proven myocarditis report a recent viral prodrome preceding cardiovascular symptoms. ECG abnormalities are often present, although the changes are frequently nonspecific. A pattern characteristic of left ventricular hypertrophy may be present. Flat or inverted T waves are most common, often with low-voltage QRS complexes. Intraventricular conduction defects and bundle branch block, especially left bundle branch block, are also common. An echocardiogram is useful to detect wall motion abnormalities or a pericardial effusion. Chest radiographs can be normal or can show evidence of congestive heart failure with pulmonary edema or cardiomegaly. Treatment depends on the type of cardiomyopathy, but may include medication, implanted pacemakers, defibrillators, or ventricular assist devices (LVADs), or ablation. The goal of treatment is often symptom relief, and some patients may eventually require a heart transplant. Treatment of cardiomyopathy (and other heart diseases) using alternative methods such as stem cell therapy is commercially available but is not supported by convincing evidence. Famous cases: In 1966, the addition of cobalt compounds to stabilize beer foam in Canada led to cardiomyopathy, which came to be known as beer drinker's cardiomyopathy Dave Williams of Drowning Pool died of cardiomyopathy in 2002. Dr. Robert Atkins, inventor of "The Atkins Diet" suffered from cardiomyopathy in the years before his death from a fall. Alexei Cherepanov, 19 year old professional ice hockey player, died of cardiomyopathy during an ice hockey game in 2008. Andy Hallett, a 33 year old actor from the television series Angel, died of congestive heart failure in 2009, brought on by a cardiomyopathy from a tooth infection five years earlier. Michael James Hegstrand aka Road Warrior Hawk an American professional wrestler. Slash, guitarist for Guns N

Roses, survived cardiomyopathy . Reggie Lewis, captain and all-star of the Boston Celtics, died from hypertrophic cardiomyopathy at age 27. Marc-Vivien Foe, Cameroonian international & West Ham United professional football (soccer) player, collapsed and died of hypertrophic obstructive cardiomyopathy (HOCM) aged 28 during a FIFA Confederations Cup Match on 26 June 2003. Cuttino Mobley, a retired NBA player who last played for the LA Clippers, was forced to retire after being diagnosed with hypertrophic cardiomyopathy in late 2008. Hank Gathers, a college basketball star recruit who played for Loyola Marymount University, collapsed during a free throw attempt against UCSB and later again against the University of Portland. The second time he never got up and was pronounced dead on arrival. Nick Carter of the Backstreet Boys was diagnosed with cardiomyopathy after suffering chest pains. Katie Gallagher, who placed second on the TV reality show Survivor: Palau, was diagnosed with viral cardiomyopathy several years later. The Amazing Jonathan was diagnosed with "a serious heart condition" in March 2007. The performer's website identified the condition as cardiomyopathy and went on to assert that, due to a combination of weight loss and blood thinners, he was doing well and did not intend to retire.

Hypertensive cardiomyopathy
Symptoms: Fatigue Irregular pulse Swelling of feet Weight gain Nausea Shortness of breath Difficulty sleeping flat in bed Bloating Greater need to urinate at night Conditions (potential complications) Left ventricular hypertrophy Coronary heart disease Congestive heart failure Hypertensive cardiomyopathy

Valvular cardiomyopathy Inflammatory cardiomyopathy Cardiomyopathy secondary to a systemic metabolic disease

Alcoholic cardiomyopathy
Alcoholic cardiomyopathy is a disease in which the chronic long-term abuse of alcohol leads to heart failure. Alcoholic cardiomyopathy is a type of dilated cardiomyopathy. Due to the direct toxic effects of alcohol on heart muscle, the heart is unable to pump blood efficiently, leading to heart failure. It can affect other parts of the body if the heart failure is severe. It is most common in males between the ages of 35-50. Symptoms presented by the occurrence of alcoholic cardiomyopathy are the result of the heart failing and usually occur after the disease has progressed to an advanced stage. Therefore the symptoms have a lot in common with other forms of cardiomyopathy. These symptoms can include: Ankle, feet, and leg swelling Overall swelling Loss of appetite Shortness of breath, especially with activity Breathing difficulty while lying down Fatigue, weakness, faintness Decreased alertness or concentration Cough containing mucus, or pink, frothy material Decreased urine output (oliguria) Need to urinate at night (nocturia) Palpitations Irregular or rapid pulse Diagnosis: Abnormal heart sounds, murmurs, EKG abnormalities, and enlarged heart on chest x-ray may lead to the diagnosis. Echocardiogram abnormalities and cardiac catheterization or angiogram to rule out coronary artery blockages, along with a history of alcohol abuse can confirm the diagnosis. Treatment for alcoholic cardiomyopathy involves lifestyle changes, including complete abstinence from alcohol use, a low sodium diet, and fluid restriction, as well as medications. Medications may include ACE inhibitors, beta blockers, and diuretics which are commonly used with other forms of cardiomyopathy to reduce the strain on the heart. Persons with congestive heart failure may be considered for surgical insertion of an ICD or a pacemaker which can improve heart function. In cases where the heart failure is irreversible and worsening, heart transplant may be considered. Treatment will possibly prevent the heart from further deterioration but is unlikely to reverse the reduced function that has already occurred.

Diabetic cardiomyopathy
Of the causes leading to cardiac dysfunction, diabetes is the most prevalent. Indeed, it is the single most important risk factor for coronary artery disease and over 30%

diabetics in the United-States are diagnosed with heart disease. Furthermore, two-thirds of diabetics will eventually die of some sort of cardiovascular disease. Aside from large vessel disease and accelerated atherosclerosis, which is very common in diabetes, diabetic cardiomyopathy (DCM) is a clinical condition diagnosed when ventricular dysfunction develops in patients with diabetes in the absence of coronary atherosclerosis and hypertension.DCM may be characterized functionally by ventricular dilation, myocyte hypertrophy, prominent interstitial fibrosis and decreased or preserved systolic function in the presence of a diastolic dysfunction. Signs & Symptoms: One particularity of DCM is the long latent phase, during which the disease progresses but is completely asymptomatic. In most cases, DCM is detected with concomitant hypertension or coronary artery disease. One of the earliest signs is mild left ventricular diastolic dysfunction with little effect on ventricular filling. Also, the diabetic patient may show subtle signs of DCM related to decreased left ventricular compliance or left ventricular hypertrophy or a combination of both. A prominent a wave can also be noted in the jugular venous pulse, and the cardiac apical impulse may be overactive or sustained throughout systole. After the development of systolic dysfunction, left ventricular dilation and symptomatic heart failure, the jugular venous pressure may become elevated, the apical impulse would be displaced downward and to the left. Systolic mitral murmur is not uncommon in these cases. These changes are accompanied by a variety of electrocardiographic changes that may be associated with DCM in 60% of patients without structural heart disease, although usually not in the early asymptomatic phase. Later in the progression, a prolonged QT interval may be indicative of fibrosis. Given that DCMs definition excludes concomitant atherosclerosis or hypertension, there are no changes in perfusion or in atrial natriuretic peptide levels up until the very late stages of the disease, when the hypertrophy and fibrosis become very pronounced. Pathophysiology: While it has been evident for a long time that the complications seen in diabetes are related to the hyperglycemia associated to it, several factors have been implicated in the pathogenesis of the disease. Etiologically, four main causes are responsible for the development of heart failure in DCM: microangiopathy and related endothelial dysfunction, autonomic neuropathy, metabolic alterations that include abnormal glucose use and increased fatty acid oxidation, generation and accumulation of free radicals, and alterations in ion homeostasis, especially calcium transients. Microangiopathy: Microangiopathy can be characterized as subendothelial and endothelial fibrosis in the coronary microvasculature of the heart. This endothelial dysfunction leads to impaired myocardial blood flow reserve as evidence by echocardiography. About 50% of diabetics with DCM show pathologic evidence for microangiopathy such as sub-endothelial and endothelial fibrosis, compared to only 21% of non-diabetic heart failure patients. Over the years, several hypotheses were postulated to explain the endothelial dysfunction observed in diabetes. It was hypothesized that the extracellular hyperglycemia leads to an intracellular hyperglycemia in cells unable to regulate their glucose uptake, most predominantly, endothelial cells. Indeed, while hepatocytes and myocytes have mechanisms allowing them to internalize their glucose transporter, endothelial cells do not possess this ability. The consequences of increased intracellular glucose concentration are

fourfold, all resulting from increasing concentration of glycolytic intermediates upstream of the rate-limiting glyceraldehyde-3-phosphate reaction which is inhibited by mechanisms activated by increased free radical formation, common in diabetes. Four pathways, enumerated below all explain part of the diabetic complications. First, it has been widely reported since the 1960s that hyperglycemia causes an increase in the flux through aldose reductase and the polyol pathway. Increased activity of the detoxifying aldose reductase enzyme leads to a depletion of the essential cofactor NADH, thereby disrupting crucial cell processes . Second, increasing fructose 6-phosphate, a glycolysis intermediate, will lead to increased flux through the hexosamine pathway. This produces N-acetyl glucosamine that can add on serine and threonine residues and alter signaling pathways as well as cause pathological induction of certain transcription factors. Third, hyperglycemia causes an increase in diacylglycerol, which is also an activator of the Protein Kinase C (PKC) signaling pathway. Induction of PKC causes multiple deleterious effects, including but not limited to blood flow abnormalities, capillary occlusion and pro-inflammatory gene expression. Finally, glucose, as well as other intermediates such as fructose and glyceraldehyde-3-phosphate, when present in high concentrations, promote the formation of advanced glycation endproducts (AGEs). These, in turn, can irreversibly cross link to proteins and cause intracellular aggregates that cannot be degraded by proteases and thereby, alter intracellular signalling. Also, AGEs can be exported to the intercellular space where they can bind AGE receptors (RAGE). This AGE/RAGE interaction activates inflammatory pathways such as NFB, in the host cells in an autocrine fashion, or in macrophages in a paracrine fashion. Neutrophil activation can also lead to NAD(P)H oxidase production of free radicals further damaging the surrounding cells. Finally, exported glycation products bind extracellular proteins and alter the matrix, cell-matrix interactions and promote fibrosis. A major source of increased myocardial stiffness is crosslinking between AGEs and collagen. In fact, a hallmark of uncontrolled diabetes is glycated products in the serum and can be used as a marker for diabetic microangiopathy. Myocardial metabolic abnormalities: Possibly one of the first difference alteration noticed in diabetic hearts were metabolic derangements. Indeed, even in the 1950s, it was recognized that cardiac myocyte from a diabetic patient had an abnormal, energy-inefficient metabolic function, with almost no carbohydrate oxidation. The changes seen in DCM are not dissimilar to those of ischemia, and might explain why diabetics are more susceptible to ischemic damage, and are not easily preconditioned. Further, diabetes leads to a persistent hyperglycemia very often accompanied by a hyperlipidemia. This alters substrate availability to the heart and surely affects its metabolism. Under normal conditions, fatty acids are the preferred substrate in the adult myocardium, supplying up to 70% of total ATP. They are oxidized in the mitochondrial matrix by the process of fatty acid -oxidation, whereas pyruvate derived from glucose, glycogen, lactate and exogenous pyruvate is oxidized by the pyruvate dehydrogenase complex, localized within the inner mitochondrial membrane. Substrate choice in the adult heart is mainly regulated by availability, energy demand and oxygen supply. Therefore, it is not surprising that alterations are present in diabetes and contribute greatly to its pathogenesis. Cardiomyocytes, unlike endothelial cells, have the ability to regulate their

glucose uptake. Thus, they are mostly spared from the complications associated with hyperglycemia that plague endothelial cells. In order to protect themselves from the extracellular hyperglycemia, cardiac cells can internalize their insulin-dependent glucose transporter, GLUT4. When looking at the carbohydrate utilization of the myocardium, diabetic hearts not only show a decrease in glucose utilization but also a very pronounced decrease in lactate utilization, to a greater extent than glucose utilization. The mechanisms are unclear but are not related to lactate transport or lactate dehydrogenase expression. Further, due to a deficient carbohydrate uptake, the diabetic myocardium shows increases in intracellular glycogen pool, possibly through augmented synthesis or decreased glycogenolysis. However, as a downside to this decrease glucose uptake, cardiomyocytes are faced with a reduced glucose oxidation rate and a dramatically increased fatty acid -oxidation to almost 100% of ATP production. This is translated into a dramatic increase of fatty acid transporter, especially CD36 that is postulated to have an important role in the etiology of cardiac disease. Interestingly, it seems that the decrease in carbohydrate oxidation precedes the appearance of hyperglycemia in type II diabetes. It is likely due to the increased oxidation due to the hyperlipidemia and altered insulin signaling. The rate of uptake of lipids, unlike that of glucose, is not regulated by a hormone. Therefore, increased circulating lipids will increase uptake and thereby fatty acid oxidation. This, in turn, increases the concentration of citrate in the cell, a very potent inhibitor of phosphofructokinase, the first rate-limiting step of glycolysis. When the rate of uptake is greater than the rate of oxidation, fatty acids are shuttled to the triglyceride synthesis pathway. Increasing triglyceride stores prevent lipotoxicity but decrease heart function. Why are all those alterations detrimental to the heart? Emerging evidence supports the concept that alterations in metabolism contribute to cardiac contractile dysfunction. In animal models, contractile failure begins as a diastolic dysfunction, and progresses occasionally to systolic dysfunction ultimately leading to heart failure. Normalizing energy metabolism in these hearts reversed the impaired contractility. During diabetes, metabolic remodeling precedes the cardiomyopathy and it is valid to hypothesize that these changes may contribute to cardiac dysfunction. Indeed, when treating animal models with metabolic modulators at an early age, prior to any sign of cardiomyopathy, improvements of heart function can be noted. Thus, it is evident that metabolic derangements seen in DCM not only precede the pathology, but also contribute greatly to its development. Autonomic neuropathy: While the heart can function without help from the nervous system, it is highly innervated with autonomic nerves, regulating the heart beat according to demand in a fast manner, prior to hormonal release. The autonomic innervations of the myocardium in DCM are altered and contribute to myocardial dysfunction. Unlike the brain, the peripheral nervous system does not benefit from a barrier protecting it from the circulating levels of glucose. Just like endothelial cells, nerve cells cannot regulate their glucose uptake and suffer the same type of damages listed above. Therefore, the diabetic heart shows clear denervation as the pathology progresses. This denervation correlates with echocardiographic evidence of diastolic dysfunction and results in a decline of survival in patients with diabetes from 85% to 44%. Other causes of denervation are ischemia from microvascular disease and thus appear following the development of microangiopathy.

Altered ion homeostasis Unlike most other cell types, the heart has constantly and rapidly changing ionic status, with various ion currents going in out of the cell during each beat cycle. More importantly, calcium is a major player of cardiac electromechanical events, energy metabolism and contractile function. It moves across the sarcolemma, sarcoplasmic reticulum and mitochondrial membranes through various organelle specific channels by active transport as well as passive diffusion. Around 30-40% of the ATP production of a cardiomyocyte is primarily used by the sarcoplasmic reticulum Ca2+-ATPase (SERCA) and other ion pumps. Thus, it is evident that any alteration in homeostasis will have serious consequences on the hearts function and possibly its integrity and structure. In DCM, such alterations have been noted since the late 80s. Indeed, studies indicate a decrease in the ability of the cell to remove Ca2+ through Na+-Ca2+ exchange and Ca2+-pump systems in the sarcolemma of diabetic rat hearts. More recently, decreased SERCA activity was shown to be a major contributor to the development of cardiac dysfunction in diabetes and decreased expression of the channel was also reported. These differences are partly explained by altered calcium signaling at the level of the ryanodine receptor, a key regulator of SERCA[37] as well as increases in phospholamban observed in diabetic hearts. Originally, these abnormalities were thought to be associated with intracellular calcium overload; however, subsequent evidence blames altered [Ca2+]i transients with unchanged basal concentrations. These alterations are not limited to calcium currents. Increases in intracellular sodium concentrations also play a causative role of ischemic damage sensitivity in diabetes and are related to a decrease in the Na+-H+ pump activity due to hyperglycemia. Furthermore, there is a decrease in a Na+-K+ ATPase subunit expression, correlating with a decrease in expression of the Na+-Ca2+ exchanger. More importantly, several potassium current abnormalities are observed. DCM causes alterations in transcription and surface expression of potassium channel proteins, which are theorized to be under the control of insulin-signaling cascade. Indeed, abnormalities in K+ can be restored in vitro following incubation with insulin. Further, altered duration of the action potential, known to be increased in DCM, was shown to result mainly from a decreased K+ transmembrane permeability Treatment: Conventional therapies At present, there is not a single clinically effective treatment for diabetic cardiomyopathy. Treatment centers around intense glycemic control through diet, oral hypoglycemics and frequently insulin and management of heart failure symptoms. There is a clear correlation between increased glycemia and risk of developing diabetic cardiomyopathy, therefore, keeping glucose concentrations as controlled as possible is paramount. Thiazolidinediones are not recommended in patients with NYHA Class III or IV heart failure secondary to fluid retention. As with most other heart diseases, angiotensin-converting enzyme (ACE) inhibitors can also be administered. An analysis of major clinical trials shows that diabetic patients with heart failure benefit from such a therapy to a similar degree as non-diabetics. Similarly, beta blockers are also common in the treatment of heart failure concurrently with ACE inhibitors. Unfortunately, their use in diabetic patients is more sensitive due to their

adverse effect on glycemia. However, one blocker in particular stands out, carvedilol. Due to its metabolic modulating properties, it was shown to be beneficial in combination with ACE inhibition, without affecting glycemia. Nutritional interventions Transition metals Given that many mechanisms involved in the pathogenesis of DCM have a basis in free radical chemistry, and that many of the anti-oxidant defenses of the cells rely on trace metals, it is worthy to consider supplementation of certain metals as part of a potential comprehensive treatment. Indeed, in rats, selenium supplementation had a possible beneficial effect on the electrical activities of the diabetic heart, possibly due to the restoration of the diminished K+ currents and partially related to a restoration of the cells glutathione redox cycle . Further, it is known that zinc deficiency is a risk factor for cardiomyopathies. Indeed, studies have shown an increased risk of developing diabetes correlating with decreased Zn concentrations as well as Zn chelators inducing diabetes in some mammalian species. While the potential of Zn to improve DCM symptoms has yet to be evaluated, its benefits have been addressed in another complication of diabetes in patients, peripheral neuropathy where it was shown to help control glycemia and attenuate some of the symptoms. Finally, a robust clinical study, although short-term, has shown that oral magnesium supplementation may be effective in reducing plasma fasting glucose levels and raising HDL cholesterol in patients with Type 2 diabetes, although the long-term benefits and safety of magnesium treatment on glycemic control remain to be determined. Thiamine Another nutritional intervention would be thiamine supplementation. As explained above, endothelial, as well as peripheral nerve dysfunctions are caused by the inability for these types of cells to regulate their glucose uptake. This results in increases of intermediates upstream of the inhibited GAPDH. It was recently shown that high thiamine supplementation activates an enzyme, transketolase, which metabolizes the accumulating glyceraldehyde-3-phosphate. This in turn prevents the complications associated with hyperglycemia. Although no clinical study was performed to corroborate these results in patients, a highly bioavailable version of thiamine was given to diabetic dogs and was shown to prevent retinopathy, a complication of diabetes related to endothelial dysfunction. In vitro, thiamine was also shown to diminish AGE production, PKC activity, inflammation and flux through the hexosamine pathway, the four causes of endothelial dysfunction. Taurine Taurine is a semi-essential sulphur amino acid derived from methionine and cysteine metabolism. Recent studies have provided a role for taurine in fetal development and in diminishing the effects of diabetes in a diabetic mother and its offspring. Furthermore, experimental data suggest that taurine could have beneficial effects in diabetes. However, clinical studies have been too small and too short to have any real significance and its effects on the heart have not been documented.

Restrictive cardiomyopathy

Restrictive cardiomyopathy (RCM) is a form of cardiomyopathy in which the walls are rigid, and the heart is restricted from stretching and filling with blood properly. It is the least common cardiomyopathy. Presentation: Rhythmicity and contractility of the heart may be normal, but the stiff walls of the heart chambers (atria and ventricles) keep them from adequately filling, reducing preload and end-diastolic volume. So blood flow is reduced, and blood that would normally enter the heart is backed up in the circulatory system. In time, restrictive cardiomyopathy patients develop diastolic dysfunction and eventually heart failure. Causes It is possible to divide the causes into primary and secondary. Primary Lffler's syndrome endocardial fibroelastosis Secondary infiltrative cardiac amyloidosis haemochromatosis sarcoidosis interstitial postradiation fibrosis Other causes include scleroderma, Churg-Strauss syndrome, cystinosis, lymphoma, Gaucher's disease, hemochromatosis, Fabry's disease, pseudoxanthoma elasticum, hypereosinophilic syndrome, carcinoid, Noonan's syndrome, reactive arthritis, and Werner's syndrome. Treatment Therapy for restrictive cardiomyopathy is limited. Diuretics may help relieve symptoms Heart failure resulting from restrictive cardiomyopathy will usually eventually have to be treated by cardiac transplantation.

Atherosclerosis
Classification and external resources Changes in endothelial dysfunction in atherosclerosis (note text comments about geometry error) Atherosclerosis (also known as Arteriosclerotic Vascular Disease or ASVD) is the condition in which an artery wall thickens as the result of a build-up of fatty materials such

as cholesterol. It is a syndrome affecting arterial blood vessels, a chronic inflammatory response in the walls of arteries, in large part due to the accumulation of macrophage white blood cells and promoted by Low-density lipoproteins (plasma proteins that carry cholesterol and triglycerides) without adequate removal of fats and cholesterol from the macrophages by functional high density lipoproteins (HDL), (see apoA-1 Milano). It is commonly referred to as a hardening or furring of the arteries. It is caused by the formation of multiple plaques within the arteries. The atheromatous plaque is divided into three distinct components: The atheroma ("lump of gruel", from , athera, gruel in Greek,), which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery Underlying areas of cholesterol crystals Calcification at the outer base of older/more advanced lesions. The following terms are similar, yet distinct, in both spelling and meaning, and can be easily confused: arteriosclerosis, arteriolosclerosis, and atherosclerosis. Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from the Greek arteria, meaning artery, and sclerosis, meaning hardening); arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries); atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque. The term atherogenic is used for substances or processes that cause atherosclerosis. Atherosclerosis, though typically asymptomatic for decades, eventually produces two main problems: First, the atheromatous plaques, though long compensated for by artery enlargement (see IMT), eventually lead to plaque ruptures and clots inside the artery lumen over the ruptures. The clots heal and usually shrink but leave behind stenosis (narrowing) of the artery (both locally and in smaller downstream branches), or worse, complete closure, and, therefore, an insufficient blood supply to the tissues and organ it feeds. Second, if the compensating artery enlargement process is excessive, then a net aneurysm results. These complications of advanced atherosclerosis are chronic, slowly progressive and cumulative. Most commonly, soft plaque suddenly ruptures (see vulnerable plaque), causing the formation of a thrombus that will rapidly slow or stop blood flow, leading to death of the tissues fed by the artery in approximately 5 minutes. This catastrophic event is called an infarction. One of the most common recognized scenarios is called coronary thrombosis of a coronary artery, causing myocardial infarction (a heart attack). Even worse is the same process in an artery to the brain, commonly called stroke. Another common scenario in very advanced disease is claudication from insufficient blood supply to the legs, typically due to a combination of both stenosis and aneurysmal segments narrowed with clots. Since atherosclerosis is a body-wide process, similar events occur also in the arteries to the brain, intestines, kidneys, legs, etc. Causes: Atherosclerosis develops from low-density lipoprotein molecules (LDL) becoming oxidized (ldl-ox) by free radicals, particularly reactive oxygen species (ROS). When oxidized LDL comes in contact with an artery wall, a series of reactions occur to repair the damage to the artery wall caused by oxidized LDL. The LDL molecule is globular shaped

with a hollow core to carry cholesterol throughout the body. Cholesterol can move in the bloodstream only by being transported by lipoproteins. The body's immune system responds to the damage to the artery wall caused by oxidized LDL by sending specialized white blood cells (macrophages and T-lymphocytes) to absorb the oxidized-LDL forming specialized foam cells. Unfortunately, these white blood cells are not able to process the oxidized-LDL, and ultimately grow then rupture, depositing a greater amount of oxidized cholesterol into the artery wall. This triggers more white blood cells, continuing the cycle. Eventually, the artery becomes inflamed. The cholesterol plaque causes the muscle cells to enlarge and form a hard cover over the affected area. This hard cover is what causes a narrowing of the artery, reduces the blood flow and increases blood pressure. Some researchers believe that atherosclerosis may be caused by an infection of the vascular smooth muscle cells. Chickens, for example, develop atherosclerosis when infected with the Marek's disease herpesvirus. Herpesvirus infection of arterial smooth muscle cells has been shown to cause cholesteryl ester (CE) accumulation. Cholesteryl ester accumulation is associated with atherosclerosis. Also, cytomegalovirus (CMV) infection is associated with cardiovascular diseases. Symptoms: Atherosclerosis typically begins in early adolescence, and is usually found in most major arteries, yet is asymptomatic and not detected by most diagnostic methods during life. Atheroma in arm, or more often in leg arteries, which produces decreased blood flow is called peripheral artery occlusive disease (PAOD). According to United States data for the year 2004, for about 65% of men and 47% of women, the first symptom of atherosclerotic cardiovascular disease is heart attack or sudden cardiac death (death within one hour of onset of the symptom). Most artery flow disrupting events occur at locations with less than 50% lumen narrowing (~20% stenosis is average). [The reader might reflect that the illustration above, like most illustrations of arterial disease, overemphasizes lumen narrowing, as opposed to compensatory external diameter enlargement (at least within smaller arteries, e.g., heart arteries) typical of the atherosclerosis process as it progresses, see Glagov[5] and the ASTEROID trial,[6] the IVUS photographs on page 8, as examples for a more accurate understanding. The relative geometry error within the illustration is common to many older illustrations, an error slowly being more commonly recognized within the last decade.] Cardiac stress testing, traditionally the most commonly performed non-invasive testing method for blood flow limitations, in general, detects only lumen narrowing of ~75% or greater, although some physicians claim that nuclear stress methods can detect as little as 50%. Atherogenesis Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of arteries involving the concomitant accumulation of fatty substances called plaques. One recent theory suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to formation of atheromatous plaques in the arterial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The bulk of these lesions is made of excess fat,

collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing, stenosis of the artery opening, called the lumen; stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerosis process by itself. Cellular Micrograph of an artery that supplies the heart with significant atherosclerosis and marked luminal narrowing. Masson's trichrome. The first step of atherogenesis is the development of so called "fatty streaks", which are small sub-endothelial deposits of monocyte-derived macrophages. The primary documented driver of this process is oxidized Lipoprotein particles within the wall, beneath the endothelial cells, though upper normal or elevated concentrations of blood glucose also plays a major role and not all factors are fully understood. Fatty streaks may appear and disappear. Low Density Lipoprotein particles in blood plasma, when they invade the endothelium and become oxidized creates a risk for cardiovascular disease. A complex set of biochemical reactions regulates the oxidation of LDL, chiefly stimulated by presence of enzymes, e.g. Lp-LpA2 and free radicals in the endothelium or blood vessel lining. The initial damage to the blood vessel wall results in a "call for help," an inflammatory response. Monocytes (a type of white blood cell) enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes. The monocytes differentiate macrophages, which ingest oxidized LDL, slowly turning into large "foam cells" so-described because of their changed appearance resulting from the numerous internal cytoplasmic vesicles and resulting high lipid content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die, and further propagate the inflammatory process. There is also smooth muscle proliferation and migration from tunica media to intima responding to cytokines secreted by damaged endothelial cells. This would cause the formation of a fibrous capsule covering the fatty streak. Calcification and lipids Intracellular microcalcifications form within vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells adjacent to the atheromas. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques. A similar form of an intramural calcification, presenting the picture of an early phase of arteriosclerosis, appears to be induced by a number of drugs that have an antiproliferative mechanism of action (Rainer Liedtke 2008). Cholesterol is delivered into the vessel wall by cholesterol-containing low-density lipoprotein (LDL) particles. To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if there is insufficient high-density lipoprotein (HDL), the lipoprotein particle that removes cholesterol from tissues and carries it back to the liver. The foam cells and platelets encourage the migration and proliferation of smooth muscle cells, which in turn ingest lipids, become replaced by collagen and transform into

foam cells themselves. A protective fibrous cap normally forms between the fatty deposits and the artery lining (the intima). These capped fatty deposits (now called 'atheromas') produce enzymes that cause the artery to enlarge over time. As long as the artery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing ("stenosis") of the opening ("lumen") occurs. The artery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an aneurysm is created. Visible features Severe atherosclerosis of the aorta. Autopsy specimen. Although arteries are not typically studied microscopically, two plaque types can be distinguished: The fibro-lipid (fibro-fatty) plaque is characterized by an accumulation of lipid-laden cells underneath the intima of the arteries, typically without narrowing the lumen due to compensatory expansion of the bounding muscular layer of the artery wall. Beneath the endothelium there is a "fibrous cap" covering the atheromatous "core" of the plaque. The core consists of lipid-laden cells (macrophages and smooth muscle cells) with elevated tissue cholesterol and cholesterol ester content, fibrin, proteoglycans, collagen, elastin, and cellular debris. In advanced plaques, the central core of the plaque usually contains extracellular cholesterol deposits (released from dead cells), which form areas of cholesterol crystals with empty, needle-like clefts. At the periphery of the plaque are younger "foamy" cells and capillaries. These plaques usually produce the most damage to the individual when they rupture. The fibrous plaque is also localized under the intima, within the wall of the artery resulting in thickening and expansion of the wall and, sometimes, spotty localized narrowing of the lumen with some atrophy of the muscular layer. The fibrous plaque contains collagen fibers (eosinophilic), precipitates of calcium (hematoxylinophilic) and, rarely, lipid-laden cells. In effect, the muscular portion of the artery wall forms small aneurysms just large enough to hold the atheroma that are present. The muscular portion of artery walls usually remain strong, even after they have remodeled to compensate for the atheromatous plaques. However, atheromas within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat, i.e., the pulse. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead to a loss of elasticity and stiffening of the artery as a whole. The calcification deposits, after they have become sufficiently advanced, are partially visible on coronary artery computed tomography or electron beam tomography (EBT) as rings of increased radiographic density, forming halos around the outer edges of the atheromatous plaques, within the artery wall. On CT, >130 units on the Hounsfield scale (some argue for 90 units) has been the radiographic density usually accepted as clearly representing tissue calcification within arteries. These deposits demonstrate unequivocal evidence of the disease, relatively advanced, even though the lumen of the artery is often still normal by angiographic or intravascular ultrasound. Rupture and stenosis Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma ulcerates which leads to immediate blood clotting at the site of atheroma ulcer. This triggers a cascade of events that leads to clot enlargement

which may quickly obstruct the lumen (opening) of the artery itself. A complete blockage leads to ischemia of the myocardial (heart) muscle and damage. This process is the myocardial infarction or "heart attack." If the heart attack is not fatal, fibrous organization of the clot within the lumen ensues, covering the rupture but also producing stenosis or closure of the lumen, or over time and after repeated ruptures, resulting in a persistent, usually localized stenosis or blockage of the artery lumen. Stenoses can be slowly progressive, whereas plaque ulceration is a sudden event that occurs specifically in atheromas with thinner/weaker fibrous caps that have become "unstable." Repeated plaque ruptures, ones not resulting in total lumen closure, combined with the clot patch over the rupture and healing response to stabilize the clot, is the process that produces most stenoses over time. The stenotic areas tend to become more stable, despite increased flow velocities at these narrowings. Most major blood-flow-stopping events occur at large plaques, which, prior to their rupture, produced very little if any stenosis. From clinical trials, 20% is the average stenosis at plaques that subsequently rupture with resulting complete artery closure. Most severe clinical events do not occur at plaques that produce high-grade stenosis. From clinical trials, only 14% of heart attacks occur from artery closure at plaques producing a 75% or greater stenosis prior to the vessel closing. If the fibrous cap separating a soft atheroma from the bloodstream within the artery ruptures, tissue fragments are exposed and released, and blood enters the atheroma within the wall and sometimes results in a sudden expansion of the atheroma size. Tissue fragments are very clot-promoting, containing collagen and tissue factor; they activate platelets and activate the system of coagulation. The result is the formation of a thrombus (blood clot) overlying the atheroma, which obstructs blood flow acutely. With the obstruction of blood flow, downstream tissues are starved of oxygen and nutrients. If this is the myocardium (heart muscle), angina (cardiac chest pain) or myocardial infarction (heart attack) develops. Diagnosis of plaque-related disease Microphotography of arterial wall with calcified (violet colour) atherosclerotic plaque (haematoxillin & eosin stain) Areas of severe narrowing, stenosis, detectable by angiography, and to a lesser extent "stress testing" have long been the focus of human diagnostic techniques for cardiovascular disease, in general. However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen narrowing present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility and sometimes sudden death. Plaques that have ruptured are called complicated plaques. The lipid matrix breaks through the thinning collagen gap and when the lipids come in contact with the blood, clotting occurs. After rupture the platelet adhesion causes the clotting cascade to contact with the lipid pool causing a thrombus to form. This thrombus will eventually grow and travel throughout the body. The thrombus will travel through different arteries and veins and eventually become lodged in an area that narrows. Once the area is blocked, blood and

oxygen will not be able to supply the vessels and will cause death of cells and lead to necrosis and poisoning. Serious complicated plaques can cause death of organ tissues, causing serious complications to that organ system. Greater than 75% lumen stenosis used to be considered by cardiologists as the hallmark of clinically significant disease because it is typically only at this severity of narrowing of the larger heart arteries that recurring episodes of angina and detectable abnormalities by stress testing methods are seen. However, clinical trials have shown that only about 14% of clinically-debilitating events occur at locations with this, or greater severity of narrowing. The majority of events occur due to atheroma plaque rupture at areas without narrowing sufficient enough to produce any angina or stress test abnormalities. Thus, since the later-1990s, greater attention is being focused on the "vulnerable plaque." Though any artery in the body can be involved, usually only severe narrowing or obstruction of some arteries, those that supply more critically-important organs are recognized. Obstruction of arteries supplying the heart muscle result in a heart attack. Obstruction of arteries supplying the brain result in a stroke. These events are lifechanging, and often result in irreversible loss of function because lost heart muscle and brain cells do not grow back to any significant extent, typically less than 2%. Over the last couple of decades, methods other than angiography and stress-testing have been increasingly developed as ways to better detect atherosclerotic disease before it becomes symptomatic. These have included both (a) anatomic detection methods and (b) physiologic measurement methods. Examples of anatomic methods include: (1) coronary calcium scoring by CT, (2) carotid IMT (intimal media thickness) measurement by ultrasound, and (3) IVUS. Examples of physiologic methods include: (1) lipoprotein subclass analysis, (2) HbA1c, (3) hs-CRP, and (4) homocysteine. The example of the metabolic syndrome combines both anatomic (abdominal girth) and physiologic (blood pressure, elevated blood glucose) methods. Advantages of these two approaches: The anatomic methods directly measure some aspect of the actual atherosclerotic disease process itself, thus offer potential for earlier detection, including before symptoms start, disease staging and tracking of disease progression. The physiologic methods are often less expensive and safer and changing them for the better may slow disease progression, in some cases with marked improvement. Disadvantages of these two approaches: The anatomic methods are generally more expensive and several are invasive, such as IVUS. The physiologic methods do not quantify the current state of the disease or directly track progression. For both, clinicians and third party payers have been slow to accept the usefulness of these newer approaches Physiologic factors that increase risk Various anatomic, physiological & behavioral risk factors for atherosclerosis are known. These can be divided into various categories: congenital vs acquired, modifiable or not, classical or non-classical. The points labelled '+' in the following list form the core components of "metabolic syndrome". Factors add to each other multiplicatively, with two factors increasing the risk of atherosclerosis fourfold. Hyperlipidemia, hypertension and cigarette smoking together increases the risk seven times.

Yet, many infarctions involve only very small amounts of tissue and are termed clinically silent, because the person having the infarction does not notice the problem, does not seek medical help or when they do, physicians do not recognize what has happened. Modifiable Having diabetes or Impaired glucose tolerance (IGT) + Dyslipoproteinemia (unhealthy patterns of serum proteins carrying fats & cholesterol): + High serum concentration of low-density lipoprotein (LDL, "bad if elevated concentrations and small"), and / or very low density lipoprotein (VLDL) particles, i.e., "lipoprotein subclass analysis" Low serum concentration of functioning high density lipoprotein (HDL "protective if large and high enough" particles), i.e., "lipoprotein subclass analysis" An LDL:HDL ratio greater than 3:1 Tobacco smoking, increases risk by 200% after several pack years Having high blood pressure +, on its own increasing risk by 60% Elevated serum C-reactive protein concentrations Nonmodifiable Advanced age Male sex Having close relatives who have had some complication of atherosclerosis (eg. coronary heart disease or stroke) Genetic abnormalities, e.g. familial hypercholesterolemia Lesser or uncertain The following factors are of relatively lesser importance, are uncertain or nonquantitated:Being obese (in particular central obesity, also referred to as abdominal or male-type obesity) + A sedentary lifestyle Postmenopausal estrogen deficiency High carbohydrate intake Intake of trans fat Elevated serum levels of triglycerides + Elevated serum levels of homocysteine Elevated serum levels of uric acid (also responsible for gout) Elevated serum fibrinogen concentrations Elevated serum lipoprotein(a) concentrations Chronic systemic inflammation as reflected by upper normal WBC concentrations, elevated hs-CRP and many other blood chemistry markers, most only research level at present, not clinically done. Stress or symptoms of clinical depression Hyperthyroidism (an over-active thyroid) Elevated serum insulin levels + Short sleep duration Chlamydia pneumoniae infection Dietary risk factors The relation between dietary fat and atherosclerosis is a contentious field. The USDA, in its food pyramid, promotes a low-fat diet, based largely on its view that fat in the

diet is atherogenic. The American Heart Association, the American Diabetes Association and the National Cholesterol Education Program make similar recommendations. In contrast, Prof Walter Willett (Harvard School of Public Health, PI of the second Nurses' Health Study) recommends much higher levels, especially of monounsaturated and polyunsaturated fat. Writing in Science, Gary Taubes detailed that political considerations played into the recommendations of government bodies. These differing views reach a consensus, though, against consumption of trans fats. The role of dietary oxidized fats / lipid peroxidation (rancid fats) in humans is not clear. Laboratory animals fed rancid fats develop atherosclerosis. Rats fed DHA-containing oils experienced marked disruptions to their antioxidant systems, as well as accumulated significant amounts of peroxide in their blood, livers and kidneys. In another study, rabbits fed atherogenic diets containing various oils were found to undergo the greatest amount of oxidative susceptibility of LDL via polyunsaturated oils. In a study involving rabbits fed heated soybean oil, "grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated". Rancid fats and oils taste very bad even in small amounts; people avoid eating them.[19] It is very difficult to measure or estimate the actual human consumption of these substances. [20] In addition, the majority of oils consumed in the United States are refined, bleached, deodorized and degummed by manufacturers. The resultant oils are colorless, odorless, tasteless and have a longer shelf life than their unrefined counterparts.[21] This extensive processing serves to make peroxidated, rancid oils much more elusive to detection via the various human senses than the unprocessed alternatives. The French paradox is the observation that despite having a diet similar to those United States in terms of fat intake, rates of heart disease are lower in France. There is evidence to suggest the French paradox is due to underestimation of the rates of heart disease in France. Prognosis Lipoprotein imbalances, upper normal and especially elevated blood sugar, i.e., diabetes and high blood pressure are risk factors for atherosclerosis; homocysteine, stopping smoking, taking anticoagulants (anti-clotting agents), which target clotting factors, taking omega-3 oils from fatty fish or plant oils such as flax or canola oils, exercising and losing weight are the usual focus of treatments that have proven to be helpful in clinical trials. The target serum cholesterol level is ideally equal or less than 4 mmol/L (160 mg/dL), and triglycerides equal or less than 2 mmol/L (180 mg/dL). Evidence has increased that people with diabetes, despite their not having clinically-detectable atherosclotic disease, have more severe debility from atherosclerotic events over time than even non-diabetics that have already suffered atherosclerotic events. Thus diabetes has been upgraded to be viewed as an advanced atherosclerotic disease equivalent. Treatment If atherosclerosis leads to symptoms, some symptoms such as angina pectoris can be treated. Non-pharmaceutical means are usually the first method of treatment, such as cessation of smoking and practicing regular exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases, and, with improvements, have increasingly become the most effective method over the long term.

However, medicines are criticized for their expense, patented control and occasional undesired effects. Statins In general, the group of medications referred to as statins has been the most popular and are widely prescribed for treating atherosclerosis. They have relatively few short-term or longer-term undesirable side-effects, and multiple comparative treatment/placebo trials have fairly consistently shown strong effects in reducing atherosclerotic disease 'events' and generally ~25% comparative mortality reduction in clinical trials, although one study design, ALLHAT, was less strongly favorable. The newest statin, rosuvastatin, has been the first to demonstrate regression of atherosclerotic plaque within the coronary arteries by IVUS (intravascular ultrasound evaluation). The study was set up to demonstrate effect primarily on atherosclerosis volume within a 2 year time-frame in people with active/symptomatic disease (angina frequency also declined markedly) but not global clinical outcomes, which was expected to require longer trial time periods; these longer trials remain in progress. However, for most people, changing their physiologic behaviors, from the usual high risk to greatly reduced risk, requires a combination of several compounds, taken on a daily basis and indefinitely. More and more human treatment trials have been done and are ongoing that demonstrate improved outcome for those people using more-complex and effective treatment regimens that change physiologic behaviour patterns to more closely resemble those that humans exhibit in childhood at a time before fatty streaks begin forming. The statins, and some other medications, have been shown to have antioxidant effects, possibly part of their basis for some of their therapeutic success in reducing cardiac 'events'. The success of statin drugs in clinical trials is based on some reductions in mortality rates, however by trial design biased toward men and middle-age, the data is as, as yet, less strongly clear for women and people over the age of 70. For example, in the Scandinavian Simvastatin Survival Study (4S), the first large placebo controlled, randomized clinical trial of a statin in people with advanced disease who had already suffered a heart attack, the overall mortality rate reduction for those taking the statin, vs. placebo, was 30%. For the subgroup of people in the trial that had Diabetes Mellitus, the mortality rate reduction between statin and placebo was 54%. 4S was a 5.4-year trial that started in 1989 and was published in 1995 after completion. There were 3 more dead women at trial's end on statin than in the group on placebo drug whether chance or some relation to the statin remains unclear. The ASTEROID trial has been the first to show actual disease volume regression (see page 8 of the paper, which shows cross-sectional areas of the total heart artery wall at start and 2 years of rosuvastatin 40 mg/day treatment); however, its design was not able to "prove" the mortality reduction issue since it did not include a placebo group, the individuals offered treatment within the trial had advanced disease and promoting a comparison placebo arm was judged to be unethical. Primary and secondary prevention Combinations of statins, niacin, intestinal cholesterol absorption-inhibiting supplements (ezetimibe and others, and to a much lesser extent fibrates) have been the most successful in changing common but sub-optimal lipoprotein patterns and group

outcomes. In the many secondary prevention and several primary prevention trials, several classes of lipoprotein expression (less correctly termed "cholesterol-lowering") altering agents have consistently reduced not only heart attack, stroke and hospitalization but also all-cause mortality rates. The first of the large secondary prevention comparative statin/placebo treatment trials was the Scandinavian Simvastatin Survival Study. (4S) with over 15 more extending through the more recent ASTEROID trial published in 2006. The first primary prevention comparative treatment trial was AFCAPS/TexCAPS with multiple later comparative statin/placebo treatment trials including EXCEL., ASCOT and SPARCL.While the statin trials have all been clearly favorable for improved human outcomes, only ASTEROID showed evidence of atherosclerotic regression (slight). For both human and animal trials, those which have shown evidence of disease regression had all utilized more aggressive combination agent treatment strategies, nearly always including niacin. Diet and dietary supplements Vitamin B3, AKA niacin, in pharmacologic doses, (generally 1,000 to 3,000 mg/day), sold in many OTC and prescription formulations, tends to improve (a) HDL levels, size and function, (b) shift LDL particle distribution to larger particle size and (c) lower lipoprotein(a), an atherosclerosis promoting genetic variant of LDL. Additionally, individual responses to daily niacin, while mostly evident after a month at effective doses, tends to continue to slowly improve further over time. (However, careful patient understanding of how to achieve this without nuisance symptoms is needed, though not often achieved.) Research work on increasing HDL particle concentration and function, beyond the usual niacin effect/response, even more important, is slowly advancing. Dietary changes to achieve benefit have been more controversial, generally far less effective and less widely adhered to with success. One key reason for this is that most cholesterol, typically 80-90%, within the body is created and controlled by internal production by all cells in the body (true of all animals), with typically slightly greater relative production by hepatic/liver cells. (Cell structure relies on fat membranes to separate and organize intracellular water, proteins and nucleic acids and cholesterol is one of the components of all animal cell membranes.) Caldwell B Esselstyn Jr. MD has had an article published in Preventive Cardiology 2001;4: 171-177 in which he has published angiograms showing regression of atherosclerosis brought about by a very low fat vegan diet in some cases with cholesterol lowering medications. While the absolute production quantities vary with the individual, group averages for total human body content of cholesterol within the U.S. population commonly run about ~35,000 mg (assuming lean build; varies with body weight and build) and ~1,000 mg/day ongoing production. Dietary intake plays a smaller role, 200300 mg/day being common values; for pure vegetarians, essentially 0 mg/day, but this typically does not change the situation very much because internal production increases to largely compensate for the reduced intake. For many, especially those with greater than optimal body mass and increased glucose levels, reducing carbohydrate (especially simple forms) intake, not fats or cholesterol, is often more effective for improving lipoprotein expression patterns, weight and blood glucose values. For this reason, medical authorities much less frequently promote the low dietary fat concepts than was commonly the case prior to about year 2005. However, evidence has increased that processed, particularly industrial non-enzymatic

hydrogenation produced trans fats, as opposed to the natural cis-configured fats, which living cells primarily produce, is a significant health hazard. Dietary supplements of Omega-3 oils, especially those from the muscle of some deep salt water living fish species, also have clinical evidence of significant protective effects as confirmed by 6 double blind placebo controlled human clinical trials. There is also a variety of evidence, though less robust, that homocysteine and uric acid levels, including within the normal range promote atherosclerosis and that lowering these levels is helpful, up to a point. In animals Vitamin C deficiency has been confirmed as an important role in development of hypercholesterolemia and atherosclerosis, but due to ethical reasons placebo-controlled human studies are impossible to do. Vitamin C acts as an antioxidant in vessels and inhibits inflammatory process. It has therapeutic properties on high blood pressure and its fluctuation, and arterial stiffness in diabetes. Vitamin C is also a natural regulator of cholesterol and higher doses (over 150 mg/kg daily) may confer significant protection against atherosclerosis even in the situation of elevated cholesterol levels. The scale of vitamin C benefits on cardiovascular system led several authors to the theory, that vitamin C deficiency is the primary cause of cardiovascular diseases. The theory was unified by twice Nobel prize winner Linus Pauling and Matthias Rath. They suggest, that clinical manifestations of cardiovascular diseases are merely overshoot of body defense mechanisms, that are involved in stabilisation of vascular wall, after it is weakened by the vitamin C deficiency and the subsequent collagen degradation. They discuss several metabolic and genetic predispositions and their pathomechanism. Trials on Vitamin E have been done, but they have failed to find a beneficial effect, for various reasons, but for some patients at high risk for atherosclerosis there may be some benefits. Menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), intake is associated with reduced risk of CHD mortality, all-cause mortality and severe aortic calcification. It has been suggested that excess iron may be involved in development of atherosclerosis, but one study found reducing body iron stores in patients with symptomatic peripheral artery disease through phlebotomy did not significantly decrease all-cause mortality or death plus nonfatal myocardial infarction and stroke.Further studies may be warranted. Surgical intervention Other physical treatments, helpful in the short term, include minimally invasive angioplasty procedures that may include stents to physically expand narrowed arteries and major invasive surgery, such as bypass surgery, to create additional blood supply connections that go around the more severely narrowed areas. Prophylaxis Patients at risk for atherosclerosis-related diseases are increasingly being treated prophylactically with low-dose aspirin and a statin. The high incidence of cardiovascular disease led Wald and Law to propose a Polypill, a once-daily pill containing these two types of drugs in addition to an ACE inhibitor, diuretic, beta blocker, and folic acid. They maintain that high uptake by the general population by such a Polypill would reduce cardiovascular mortality by 80%. It must be emphasized however that this is purely theoretical, as the Polypill has never been tested in a clinical trial.

Medical treatments often focus predominantly on the symptoms. However, over time, the treatments which focus on decreasing the underlying atherosclerosis processes, as opposed to simply treating the symptoms resulting from the atherosclerosis, have been shown by clinical trials to be more effective. In summary, the key to the more effective approaches has been better understanding of the widespread and insidious nature of the disease and to combine multiple different treatment strategies, not rely on just one or a few approaches. In addition, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, adopting more aggressive combination treatment strategies has generally produced better results, both before and especially after people are symptomatic. Because many blood thinners, particularly salicylates such as warfarin and aspirin thin the blood by interfering with Vitamin K, there is recent evidence that blood thinners which work by this mechanism, can actually worsen arterial calcification in the long term even though they thin the blood in the short term. Recent research An indication of the role of HDL on atherosclerosis has been with the rare Apo-A1 Milano human genetic variant of this HDL protein. A small short-term trial using bacterial synthetized human Apo-A1 Milano HDL in people with unstable angina produced fairly dramatic reduction in measured coronary plaque volume in only 6 weeks vs. the usual increase in plaque volume in those randomized to placebo. The trial was published in JAMA in early 2006. Ongoing work starting in the 1990s may lead to human clinical trials probably by about 2008. These may use synthesized Apo-A1 Milano HDL directly. Or they may use gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDLipoprotein. Methods to increase high-density lipoprotein (HDL) particle concentrations, which in some animal studies largely reverses and remove atheromas, are being developed and researched. Niacin has HDL raising effects (by 10 - 30%) and showed clinical trial benefit in the Coronary Drug Project and is commonly used in combination with other lipoprotein agents to improve efficacy of changing lipoprotein for the better. However most individuals have nuisance symptoms with short term flushing reactions, especially initially, and so working with a physician with a history of successful experience with niacin implementation, careful selection of brand, dosing strategy, etc. are usually critical to success. However, increasing HDL by any means is not necessarily helpful. For example, the drug torcetrapib is the most effective agent currently known for raising HDL (by up to 60%). However, in clinical trials it also raised deaths by 60%. All studies regarding this drug were halted in December 2006. The ASTEROID trial used a high-dose of rosuvastatinthe statin with typically the most potent dose/response correlation track record (both for LDLipoproteins and HDLipoproteins.) It found plaque (intima + media volume) reduction. Several additional rosuvastatin treatment/placebo trials for evaluating other clinical outcomes are in progress. The actions of macrophages drive atherosclerotic plaque progression. Immunomodulation of atherosclerosis is the term for techniques which modulate immune system function in order to suppress this macrophage action.[56] Immunomodulation has been pursued with

considerable success in both mice and rabbits since about 2002. Plans for human trials, hoped for by about 2008, are in progress. Research on genetic expression and control mechanisms is progressing. Topics include PPAR, known to be important in blood sugar and variants of lipoprotein production and function; The multiple variants of the proteins that form the lipoprotein transport particles. Some controversial research has suggested a link between atherosclerosis and the presence of several different nanobacteria in the arteries, e.g., Chlamydophila pneumoniae, though trials of current antibiotic treatments known to be usually effective in suppressing growth or killing these bacteria have not been successful in improving outcomes. The immunomodulation approaches mentioned above, because they deal with innate responses of the host to promote atherosclerosis, have far greater prospects for success. The National Heart, Lung, and Blood Institute (NHLBI) and National Center for Complementary and Alternative Medicine (NCCAM) sponsored The Trial to Assess Chelation Therapy (TACT). The purpose of this study is to determine the safety and effectiveness of ethylene diamine tetra-acetic (EDTA) chelation therapy in individuals with coronary artery disease. EDTA chelation therapy involves repeated administrations of a synthetic amino acid to reduce atherosclerotic plaque and other mineral deposits throughout the cardiovascular system. The results of TACT will provide either a significant positive result or an informative null result upon which rational clinical decision-making and health policy can be based. The Hemorheologic-Hemodynamic Theory The theory of atherogenesis described above is presented largely as fact. While representing the mainstream view, this theory has several weaknesses. Aggressive reduction of serum LDL-cholesterol using high dose statin therapy still leaves significant risk of adverse cardiovascular events in high-risk patients. Despite lowering serum LDLcholesterol to less than 100 mg/dL, the estimated risk of adverse events in patients with established coronary artery disease is estimated to be 9% per year. This, in conjunction with the failure of torcetrapib in clinical trials, should prompt reexamination of mainstream atherogenesis theory. Further, oxidized LDL is widely distributed in both arteries and veins, the latter of which do not develop atherosclerosis. The distribution of the putative precursor lesion, the fatty streak, correlates poorly with the distribution of fibrous plaques. The mainstream theory of atherogenesis does not explain the localization of fibrous plaques to the vicinity of changing arterial geometry, such as branches, curves, and dilatations. Mainstream theory provides no explanation for accelerated atherosclerosis associated with hypertension. Finally, mainstream theory cannot explain the presence of fibrous plaques in synthetic arteriovenous grafts. The hemorheologichemodynamic theory holds that atherosclerosis is a disease of stasis of blood, which promotes the organization of a thrombus into an atherosclerotic plaque.Stasis of blood predisposes to thrombosis, as described in Virchow's triad. Risk factors for atherosclerosis create larger areas of decreased shear (flow) by increasing blood viscosity, arterial stiffness, or both. Both of these abnormalities are seen in association with aging, hypertension, diabetes mellitus, cigarette smoking, and obesity. The hemorheologichemodynamic theory posits that the same pathologic process, thrombosis, leads to both plaque development and its complication, superimposed thrombosis and infarction. The name reflects the fact that the interaction of hemorheologic, i.e., blood flow, and

hemodynamic, i.e., blood velocity, pulsatility, and arterial geometry, factors lead to atherosclerosis. Viscosity and localized stasis In arteries during systole, there is a gradient of blood velocity with the highest velocity in the center of the vessel and the lowest against the arterial wall. In areas of vascular branching, curving and dilatation, focal blood pooling occurs in the low shear environment against the arterial wall if blood velocity exceeds a critical value of Reynolds number (see below). This phenomenon is seen in nature when rapidly flowing water encounters an obstruction, forming eddies and pools. Blood is a non-Newtonian fluid, and its viscosity progressively increases with decreasing shear. In areas of pooling, a vicious cycle can develop in which increased viscosity leads to decreased flow, further increasing viscosity and decreasing flow, leading ultimately to stasis and thrombosis in the absence of adequate fibrinolytic activity. Decreased blood flow promotes thrombosis by decreasing influx of fibrinolytic molecules and decreasing efflux of activated clotting factors. Platelets activated by high shear in the central column of blood can be directed to the vicinity of the arterial wall by eddy currents. In these areas, decreased blood flow decreases endothelial production of molecules with antithrombotic activity such as nitric oxide and prostacyclin, further promoting thrombosis. This is akin to endothelial dysfunction which in mainstream atherogensis theory is thought to be caused by putative cytopathic effects of oxidized lowdensity lipoprotein. Arterial stiffening Increased arterial stiffness accelerates atherosclerosis by increasing peak arterial blood velocity, thereby increasing Reynold's number, which indicates the propensity for a flowing fluid to develop pools and eddy currents in association with changing arterial geometry. In the normally compliant aorta, a portion of each stroke volume is stored in systole and propelled with lower velocity in diastole, creating blood flow throughout most of the cardiac cycle. An area of pooling created by high velocity would disappear during slow diastolic flow, and any accumulated microthrombus would be dispersed. In a perfectly stiff aorta, the entire stroke volume would be expelled in systole. Given constant stroke volume, conservation of mass requires increasing peak arterial blood velocity with increasing arterial stiffness.[63] In addition, no low velocity diastolic flow will occur, so that a pool formed during high velocity systolic flow will persist throughout the cardiac cycle. This will allow the time necessary for thrombus growth and subsequent organization (see below). Additionally, increased peak arterial velocity will augment shear-mediated platelet activiation. Organization of mural thrombi J.B. Duguid promoted the idea that atherosclerotic plaques develop from organization of mural thrombi in the 1940s and 50's. Arterial thrombi tend to remain localized to the low shear environment of the arterial wall because of high blood velocity in the central portion of the artery. These thrombi are know as "mural" or "parietal." In veins, the velocity gradient between the center of the vessel and the vessel wall is small. Thus, thrombi in veins are more likely to become occlusive, as in deep venous thrombosis. This is why atherosclerosis is limited to arteries. If thrombi persist, whether in arteries or veins, they undergo organization, in which circulating fibrocytes colonize the thrombus and

differentiate into cells capable of producing collagen and markers of smooth muscle differentiation, such as smooth muscle actin. Role of lipoproteins in atherogenesis The hemorheologic-hemodynamic theory predicts that low-density lipoprotein (LDL) should increase blood viscosity and high-density liporotein (HDL) should decrease blood viscosity, which has been demonstrated experimentally. Erythrocytes are separated by a minimum intercellular distance of approximately 15 nanometers caused by electrostatic repulsion due to sialic acid on the cell membrane surface. LDL has a particle diameter of 18 to 40 nanometers, large enough to simultaneously bind to two erythrocytes and form erythrocyte aggregates. Erythrocyte aggregates increase blood viscosity at low shear by increasing the inertia of the suspended particles. HDL, with a particle diameter of 8 to 12 nanometers, is too small to promote erythrocyte aggregation. Instead, by competing with LDL for binding to erythrocytes, it antagonizes erythrocyte aggregation and decreases blood viscosity. Erythrocyte aggregates are weak, and progressively distrupted with increasing shear. Given the relationship of LDL to blood viscosity, it is not surprising that hypercholesterolemia is a risk factor for both atherosclerosis and deep venous thrombosis. The hemorheologic-hemodynamic theory explains the significant remaining risk of adverse cardiovascular events in patients with established coronary artery disease despite aggressive lowering of LDL-cholesterol using high dose statin therapy. Despite lowering serum LDL-cholesterol to less than 100 mg/dL, the risk of major cardiovascular events in these patients is estimated to be 9% per year. Such therapy does not address the adverse consequences of arterial stiffening, or increased blood viscosity caused by other factors. The hemorheologic-hemodynamic theory explains the existence of atherosclerotic plaques in synthetic arteriovenous grafts. These provide an extreme hemodynamic environment, where extremely high velocity blood flows through a curved vessel. These vessels are prone to thrombosis and development of atherosclerotic plaques despite anticoagulation. These vessels lack a tunica media, which received wisdom maintains is the origin of smooth muscle cells in atherosclerotic plaques via migration. The identification of the fibrocyte provides an alternative explanation for the origin of smooth muscle cells in atherosclerotic plaques. Being largely inanimate, the capacity of these vessels to respond to an injury with an inflammatory response, the inciting cause of atherosclerosis according to mainstream atherogenesis theory, would be very limited. Further, this theory explains the benefit of blood donation and drinking large quantities of water. Both of these very low risk interventions reduce blood viscosity. The hemorheologic-hemodynamic eliminates reliance on the fatty streak in atherogenesis. Fatty streaks routinely resolve without sequelae. This is acknowledged in by mainstream atherogenesis theory, which is unable to predict why a particular fatty streak progresses into an atherosclerotic plaque while the majority regress. Increased HDL particle size and increased low-shear blood viscosity caused by torcetrapib therapy could account for the increased cardiovascular mortality seen in clinical trials. Increased peak arterial blood velocity and arterial stiffening may also play a role in sudden cardiac death associated with physical exertion. Physical exertion results in increased cardiac output and increased blood pressure, both of which could increase peak arterial velocity, although the effect of increased cardiac output on peak arterial blood velocity in this situation has not been studied. Increased Reynolds number could lead to acute coronary thrombosis as described above.

The future Validation of the hemorheologic-hemodynamic theory will require a prospective study to determine if measuring blood viscosity and peak arterial blood velocity identifies subjects at high risk for symptomatic atherosclerosis better than routine markers such as lipid analysis.

Bibliography: http://en.wikipedia.org/wiki/Heart_diseases

WORD
1. Aging

DEFINITION
The process of becoming older, a process that is genetically determined and environmentally modulated. Inflammation of a joint. When joints are inflamed they can develop stiffness, warmth, swelling, redness and pain. Wasting away or diminution. Abnormal buildup of fluid in the abdomen. Without symptoms. Anything, and especially a drug, used to prevent or treat depression. Another name for the intestine . The small bowel and the large bowel are the small intestine and large intestine , respectively. The spine. An abnormal and persistent fear of depths. A water-soluble B-complex vitamin involved in carbon dioxide transfer and therefore essential to the metabolism of carbohydrate and f at. An illness caused by the parasite Babesia which is transmitted from animals to humans by ticks. A normal process to relieve distention from the air that accumulates in the stomach. Physical wasting with loss of weight and muscle mass caused by disease. Cancer that begins in the skin or in tissues that line or cover body organs. A rapid expulsion of air from the lungs typically in order to clear the lung airways of fluids, mucus, or

TRANSLAT PHONETIC ION TRANSLATION

Imbatranire

ed

2. Arthritis

Artrit

arrajts

3. Atrophy 4. Ascites 5. Asymptomatic 6. Antidepressant 7. Bowel

Atrofie Ascit Asimptomatic Antidepresiv Intestin

trfi zsajts esmptmtk ntidprsnt bal

8. Backbone 9. Bathophobia 10. Biotin

Sira spinrii Batofobia Botin

bkbn bfbi btn

11. Babesiosis

Babesioza

b bzss

12. Belching 13. Cachexia 14. Carcinoma

Rgial Casexie Carcinomul

belt kkeks ksnm kf

15. Cough

Tuse

16. Chancre 17. Chilblain

material. Also called tussis. The classic painless ulcer of syphilis. A cold injury which, while painful, causes little or no permanent impairment. The major metabolite (breakdown product) of nicotine. Partial or complete hearing loss. To burst open or gape. To remove the moisture from a thing that normally contains moisture, such as a plant; to dry out completely; to preserve by drying. Colorblindness of the red-green type, also known as deuteranomaly or Daltonism. Painful or difficult urination. A device for removing fluid from a cavity or wound. The swelling of soft tissues as a result of excess water accumulation. The tympanic membrane of the ear, or tympanum. Convulsions (seizures) occurring with pregnancy-associated high blood pressure and having no other cause. Being without teeth. An attack of bleeding from the nosed. A rash inside the body. A condition characterized by a lessened capacity for work and reduced efficiency of accomplishment, usually accompanied by a feeling of weariness and tiredness. In anatomy, a vaultlike or arched structure. The throat. Damage to tissues from freezing due to the formation of ice crystals within cells, rupturing the cells and leading to cell death. Healthy skin, bone, or other tissue taken from one part of the body to replace diseased or injured tissue removed from another part of the body. A manner of walking.

Sancru Degertur

akr tlblen ktnn defnes dihis desikt

18. Cotinine 19. Deafness 20. Dehisce 21. Desiccate

Cotinina Surditate A se deschide brusc A deshidrata

22. Deuteranopia 23. Dysuria 24. Drain 25. Edema 26. Eardrum 27. Eclampsia 28. Edentulous 29. Epistaxis 30. Enanthem 31. Fatigue

Deuteranopie Disurie Drena Edem Timpan Eclampsie Edentat Epistaxis Enantem Oboseal

dtrnp disyu r drn idm irdrm iklamps denchls epstakss inantm ftg

32. Fornix 33. Fauces 34. Frostbite

Fornix Beregat Degeratura

foniks r fo sz frobt s

35. Graft

Grefa

graft

36. Gait

Pit

gt

37. Goiter 38. Galactorrhea 39. Greensickness 40. Glioma 41. Halitosis 42. Hantavirus 43. Hematuria 44. Hamstring 45. Hemangioma 46. Hysterectomy 47. Inclusion

48. Ichthyosis 49. Ileus 50. Immunocompromised 51. Itching

52. Interferon 53. Jaundice 54. Juxtapyloric 55. Kinesthesis 56. Keratoderma 57. Kymograph

An enlargement of the thyroid gland , that often results from insufficient intake of iodine. The spontaneous flow of milk from the nipple at any time other than during nursing. An iron-deficiency anemia especially of adolescent girls that may impart a greenish tint to the skin A brain tumor that begin in a glial cell, in the brain or spinal cord. Bad breath. A group of viruses that cause hemorrhagic fever and pneumonia. Blood in the urine. The prominent tendons at the back of the knee. A birth irregularity where a localized tissue mass grows rich in small blood vessels. Surgical removal of the uterus. Something that is included; especially : a passive usually temporary product of cell activity within the cytoplasm or nucleus. Dry, rectangular scales on the skin. Obstruction of the intestine due to it being paralyzed. Having an immune system that has been impaired by disease or treatment. An uncomfortable sensation in the skin that feels as if something is crawling on the skin or in the skin, and makes the person want to scratch the affected area. A naturally occurring substance that interferes with the ability of viruses to reproduce. Yellow staining of the skin and sclerae by abnormally high blood levels of the bile pigment bilirubin. Means near the pylorus. Sensory experience derived from this sense. A horny condition of the skin. A type of brain damage associated with athetoid cerebral palsy and

Gusa Galactoreea Cloroza Glioma Halen Virusul lui Hantaan Hematurie Tendon popliten Hemangiom Bisterectomie Incluziune

go itr glaktr grnsikns glm haltss hantvrs hmtu r hamstri hmanjm histrektm in-kl-zhn

Ihtioz Ocluzie intestinal Imunocompromis Mancarime

iktss ils imynkmpr mzd t

Interferon Icter Juxtapiloric Anestezie Keratodermie Chimograf

intrfirn jo ds n jkstplrik kinstz kertdrm kmgraf

58. Kinesin 59. Kyphosis 60. Leukopenia 61. Lymphoma 62. Lithiasis 63. Laceration 64. Laparotomy 65. Leptin 66. Leishmania 67. Levocardia

68. Macrogenitosomia 69. Malaise 70. Mycology 71. Meconium 72. Melasma

73. Menorrhagia 74. Nystagmus 75. Nausea 76. Narcolepsy

77. Neonatal

deafness. A family of microtubule motor proteins active in mitosis. Outward curvature of the spine, causing a humped back. Lower than the normal amount of white blood cells. Tumor of the lymphoid tissue. The formation of stony concretions in the body (as in the gallbladder) The act of lacerating. An operation to open the abdomen. A hormone that has a central role in fat metabolism. A group of parasites causing a disease called leishmaniasis. Reversal of all of the abdominal and thoracic organs except the heart, which is still in its usual location on the left. Condition in which the external sex organs are prematurely enlarged or abnormally enlarged. A vague feeling of discomfort, one that cannot be pinned down but is often sensed as "just not right." A branch of biology dealing with fungi. Dark sticky material normally present in the intestine at birth and passed in the feces after birth. Pigmentation of the face, most commonly on the malar area, bridge of nose, forehead, and upper lip, that occurs in half of women during pregnancy. Excessive uterine bleeding occurring at the expected intervals of the menstrual periods. A rapid involuntary oscillation of the eyeballs. The urge to vomit. A condition characterized by brief attacks of deep sleep often occurring with cataplexy and hypnagogic hallucinations. Pertaining to the newborn period which, by convention, is the first four

Kinezina Cifoza Leucopenie Limfomul Litiaza Rupere Laparotomie Leptina Leishmania Sinistrocardie

kinsn kfss lkpn limfm litss lasrshn laprtm leptn lman lvkrd

Macrogenitosomie Indispoziie Micologie Meconiu Melasma

makrjenit sm mlez mklj miknm mlazm

Menoragie Nistagmus Grea Narcolepsie

menrj nistagms no z nrkleps

Neonatal

nntl

78. Noma

79. Nexus 80. Omentum 81. Omphalocele

82. Olfaction 83. Oxyuriasis 84. Ototoxic 85. Platelet 86. Perionychium 87. Pyrosis 88. Putamen 89. Puerperium 90. Pruritus 91. Qualm 92. Queasy 93. Quadriplegic 94. Quinacrine 95. Ranula 96. Rash 97. Recurrence

weeks after birth. A spreading invasive gangrene chiefly of the lining of the cheek and lips that is usually fatal and occurs most often in persons severely debilitated by disease or profound nutritional deficiency. A connection or link. A causal connection. A sheet of fat that is covered by peritoneum. A birth defect in which part of the intestine, covered only by a thin transparent membrane, protrudes outside the abdomen at the umbilicus. The sense of smell, part of the chemical sensing system, or the chemosenses. Infestation with or disease caused by pinworms (family Oxyuridae). Producing, involving, or being adverse effects on organs or nerves involved in hearing or balance. An irregular, disc-shaped element in the blood that assists in blood clotting. The tissue bordering the root and sides of a fingernail or toenail. A technical term for what is popularly called heartburn, a burning sensation in the upper abdomen. An area in the brain within a structure called the lentiform nucleus. The time immediately after the delivery of a baby. To have an itch. Sickness, disease, pestilence, or death. A feeling of nausea. One affected with paralysis of both arms and both legs. An antimalarial drug and, in cytogenetics, a fluorescent dye used to stain chromosomes. A cyst formed under the tongue by obstruction of a gland duct. Breaking out (eruption) of the skin. The return of a sign, symptom or disease after a remission.

Noma

nm

Nexus Epiploon Omfalocelul

nekss mentm mflsel

Olfactiv oxiuroz Ototoxica Trombocit Perionix Pirozisul Putamen Puerperiumul Prurit Remucare Greos Cvadriplegic Chinacrina Ranula Erupie cutanat Recuren

lfakshn ksiyurss ttksik pltlt pernikm prss pytmn pyrpirm prrts kwm kwz kwdrpljik kwinkrn ranyl r rikrns

98. Reuptake 99. Remission 100. Resectable 101. Rib 102. Rachitis

103. Semen 104. Serum 105. Scoliosis 106. Seizure

107. Shin 108. Synesthesia 109. Tetany

110. Taeniasis 111. Taint 112. Telomere

113. Trochanter 114. Trichobezoar 115. Tarantism 116. Uricaciduria

The reabsorption of a secreted substance by the cell that originally produced and secreted it. Disappearance of the signs and symptoms of cancer or other disease. Able to be removed by surgery. One of the 12 paired arches of bone which form the skeletal structure of the chest wall. A deficiency disease that affects the young during the period of skeletal growth, is characterized especially by soft and deformed bones, and is caused by failure to assimilate and use calcium and phosphorus normally due to inadequate sunlight or vitamin D. The fluid that is released through the penis during orgasm. The clear liquid that can be separated from clotted blood. Sideways (lateral) curving of the spine. Uncontrolled electrical activity in the brain, which may produce a physical convulsion, minor physical signs, thought disturbances. The tibia, the larger of the two bones in the lower leg. A condition in which normally separate senses are not separate. A condition of physiological calcium imbalance that is marked by intermittent tonic spasm of the voluntary muscles. Infection with any of the tapeworms of the genus Taenia. To poison, infect, or spoil. The end of a chromosome, a specialized structure involved in the replication and stability of the chromosome. One of the bony prominences toward the near end of the thigh bone. A wad of swallowed hair,also called a hairball. A disease once thought to result from the bite of the tarantula spider. The presence of excess uric acid in

Reabsorbtie Remisie Sectionabil Coasta Rahitism

rptk rimin risektbl rib rkts

Sperma Ser Scolioza Atac de apoplexie

smn sirm sklss sr

Tibie Sinestezie Tetanie

in sinst tetn

Teniaza A infecta Telomerul

tnss teint telmir

Trohanter Tricobezoar Tarantism Uricaciduria

trkantr trikbzr tarntizm yuikasdyu r r

117. Urate 118. Ubiquitin 119. Variolation 120. Vasculitis 121. Viremia 122. Viscus 123. Vertebroplasty 124. Vesicant 125. Vitrectomy 126. Vallecula 127. Valetudinarian

128. Vaginitis 129. Windpipe

130. Wheezing 131. Walleye 132. Warble 133. Wart 134. Wasting 135. Wrist

the urine, which may be a sign of gout or kidney stones. A salt of uric acid. A small but extremely important protein that acts the "kiss of death" to other proteins. The old practice of inoculating someone with the virus of smallpox to produce immunity to the disease. A general term for a group of diseases that feature inflammation of the blood vessels. The presence of a virus in the blood. An internal organ of the body, specifically one within the chest or abdomen. A nonsurgical method for the repair of vertebral fractures and compression due to osteoporosis. A substance that causes tissue blistering. Removal of the gel (called the vitreous) from within the eyeball. An anatomic term for a crevice, furrow or depression. Someone with a weak or sickly constitution, especially someone whose chief concern is being or becoming a chronic invalid. Inflammation of the vagina. The trachea, a tube-like portion of the respiratory tract that connects the larynx with the bronchial parts of the lungs. A whistling noise in the chest during breathing when the airways are narrowed or compressed. A dense white opacity (leukoma) of the cornea. A small hard nodule produced by the larva of a fly that has penetrated the skin. A local growth of the outer layer of the skin (the epidermis) caused by a virus. Gradual loss, deterioration, emaciation. The proximal segment of the hand consisting of the carpal bones and the associated soft parts.

Urat Ubiquitin Variolare Vasculita Viremie Viscer Vertebroplastie Vezicant Vitrectomie Valecula Ipohondru

yut r ybikwtn varln vaskylts vrm visks vrtbrplast vesiknt vtrektm valekyl valtydnern

Vaginita Traheea

vajnts windpp

Sforait Leucomul Nodul Neg Deteriorare ncheietura

wzi wo l wobl r wot r wsti rist

136. Womb

137. Xanthopsia

138. Xanthine

139. Xenoantigen 140. Xenograft 141. Xanthoma

142. Xerosis 143. Xenobiotic 144. Yeast 145. Yaws

146. Yawning 147. Zoophobia 148. Zoonosis 149. Zolmitriptan 150. Zyrtec

The uterus, is a hollow pear-shaped organ located in a woman's lower abdomen between the bladder and the rectum. A form of chromatopsia, a visual defect in which objects appear as if they have been overpainted with an unnatural color. A substance found in caffeine, theobromine, and theophylline and encountered in tea, coffee, and the colas. An antigen that is found in more than one species. A surgical graft of tissue from one species to an unlike species (or genus or family). Yellowish firm nodules in the skin frequently indicating underlying disease, such as diabetes, disorder of fats or other conditions. Abnormal dryness of the skin, of the conjunctiva of the eye. Natural substances that are foreign to the body. A group of single-celled fungi that reproduce by budding. A common chronic infectious disease that occurs mainly in the warm humid regions of the tropics with characteristic bumps on the skin of the face, hands, feet and genital area. Involuntary opening of the mouth with respiration, breathing first inward, then outward. An abnormal and persistent fear of animals. An infectious disease in animals that can be transmitted to people. A triptan drug for the treatment of migraine. Used for a preparation of the dihydrochloride of cetirizine.

Pntec

wm

Xantopsie

zantps

Xantina

zantn

Xenoantigen Xenogrefa Xantom

zenantijn zengraft zantm

Xeroza Xenobiotici Drojdie Framboesia

zirss zenbtik, yst yo z

Cscat Zoofobie Zoonoz Zolmitriptan Zirtec

yni zfb znss zlmitriptan zrtek

BOLILE INIMII
Bolile inimii sau cardiopatia este un termen cheie pentru o varietate de boli diferite care afecteaz inima. ncepnd din 2007, este principala cauz de deces n Statele Unite, Anglia, Canada i ara Galilor unde o persoana moare la fiecare 34 de secunde n Statele Unite . Tipuri de boli de inim: boal coronarian, cardiomiopatie, boli cardiovasculare, boli de inima ischemice, insuficien cardiac hipertensiva, boli inflamatorii de inim, boli de inim valvulare. Boala coronarian se refer la ntreruperea circulaiei coronariene de a furniza o circulaie adecvat a muchiului cardiac i esutului din jur. Boala coronarian este cel mai frecvent asimilat cu o boal coronarian arterial, dei aceast boal coronarian poate fi datorat altor cauze, cum ar fi vasospasmul coronarian. Boala coronarian arterial este o boal a arterei cauzate de acumularea de plci ateroamateus n pereii arterelor care alimenteaz miocardul. Angin pectoral (durere n piept) i infarct miocardic (atac de cord) sunt simptomele i condiiile cauzate de aceast boal.Peste 459,000 de americani mor de aceast boal n fiecare an. n Regatul Unit, 101,000.

Boli de inim Coronariene

Cardiomiopatie literalmente nseamn "boala muchiului inimii" (Myo = muchi, pathy = boala) Este deteriorarea funciei de miocard (de exemplu, muchiul inimii reale) pentru orice motiv. Oamenii cu cardiomiopatie sunt adesea expui riscului de aritmie i / sau moarte subit de cauz cardiac. Cardiomiopatia extrinseac cardiomiopatiile erau patologia primar n afara de miocardul n sine. Cele mai multe sunt cardiomiopatii extrinseci, pentru c, de departe, cea mai frecvent cauz a unei cardiomiopatii este ischemia. Organizaia Mondial a Sntii amintete aceste cardiomiopatie specifice. Boli de inim Congenitale Un defect congenital cardiac (DCC) este un defect n structura inimii si vasele mari de snge unui nou-nscut. Cele mai multe defecte ale inimii, fie obstrucioneaz fluxul de snge n vasele inimii sau n apropierea acesteia sau provoc sngele s curga prin inima ntr-un mod anormal, cu toate c a altor defecte care afecteaz ritmul cardiac (cum ar fi sindromul de QT prelungit) pot aprea, de asemenea. Defectele de inima sunt printre cele mai frecvente defecte congenitale i sunt cauza principala a defectelor de natere ducand la decese. Semnele i simptomele sunt legate de tipul i severitatea defectului inimii. Unii copii nu au nici un semn, n timp ce alii pot prezenta dificulti de respiraie, cianoz, dureri n piept, sincopa,

Cardiomiopatia

transpiraii, murmur cardiac, infecii respiratorii, fr poft de mncare, sau cretere slab , acumularea de snge i de lichid n plmni, picioarelor, gleznelor i picioarelor. Medicii pot detecta uneori cu stetoscopul. Cu toate acestea, toate murmurele inimii nu sunt cauzate de defecte cardiace congenitale. Simptome CDD frecvent prezente la nceputul anului de via, dar este posibil ca unele CDDs pentru a merge nedetectate pe tot parcursul vieii. Cauza se poate datora unei predispoziie genetice sau de o expunere n mediu n timpul sarcinii.Cunoscute cauze genetice ale bolilor de inim, includ anomalii cromozomiale, cum ar fi trizomiile 21, 13, i 18, precum i o gam de recent recunoscute, mutaii genetice punct, punct i eliminrile alte anomalii genetice aa cum se vede n sindroamele, cum ar fi Velo-Cardio-faciala Sindromul, ASD familial cu bloc cardiac, sindrom Alagille, sindrom Noonan, si multe altele. Cunoscut factorilor de mediu antenatale includ infecii matern (rubeolic), medicamente (alcool, hydantoin, litiu i talidomid), i a bolilor profesionale matern diabet (diabet, fenilcetonurie, i lupus eritematos sistemic). Clasificare: Hipoplazia pot afecta inima, care de obicei ca rezultat eecul fie a ventriculului drept sau ventriculului stng de a dezvolta n mod adecvat, lsnd doar o parte a inimii capabil s pompeze snge pentru organism i plmni. Hipoplazia inimii este rar, dar este forma cea mai grav a BIC, ea este numit sindromul hipoplastic stng cnd acestea afecteaz partea stanga a inimii i sindromul hipoplastic drept I cnd acestea afecteaz partea dreapt a inimii. n ambele condiii, prezena unui brevet canalului arterial (i, atunci cnd hipoplazie afecteaz partea dreapt a inimii, un foramen ovale patent), este vital pentru capacitatea copilului de a supravieui pn la chirurgie cardiac de urgen pot fi efectuate, deoarece fr aceste ci de snge nu pot circula n organism (sau plmni, n funcie de care parte a inimii este defect). Hipoplazia inimii este, n general, un defect cianotic. Defectele obstrucionri apar atunci cnd valvele cardiace, artere, sau venele sunt anormal de inguste sau blocate. Defecte de obstrucie frecvent, includ stenoza valva pulmonar, stenoz aortic supap, precum i nsprirea aortei, cu alte tipuri, cum ar fi stenoza bicuspid valva Stenoz aortic i subaortic fiind relativ rare. Orice ngustare sau blocarea a inimii poate provoca extindere sau hipertensiune arterial. Septul este un perete, esut care separ partea sng a inimii de cea stng. Este relativ comun pentru ca defectele s existe n septul interatrial sau septul interventricular, permind sngelui trecerea din partea stanga a inimii la dreapta, reducnd eficiena inimii. Defecte septale ventriculare sunt colective, cel mai frecvent tip de CDD, dei aproximativ 30% dintre aduli au un tip de defect septal atrial numit foramen ovale sonda de brevete. Defecte septale pot sau nu pot provoca cianoz, n funcie de severitatea defectului.

Defectele inimii cianotice sunt numite astfel, deoarece acestea rezultat cianoz, o decolorare gri-albstruie a pielii din cauza lipsei de oxigen n organism. Astfel de defecte includ arterial TRUNCUS persistente, n total conexiune anormale pulmonar venos, tetralogie Fallot, transpunere a navelor de mare, i Atrezie tricuspid. Defecte: Stenoz aortic Defect septal atrial (DSA) Defect septal atrioventricular (DSAV) Sindromul Brugada Cardiomiopatie Dextrocardia Sindromul DiGeorge Dubla admisie a ventriculului stng(DAVS) Dublu admisie a ventriculului drept (DAVD) Anomalia Ebstein Hipoplazica stnga sindromul inimii (HSSI) Sindromul hipoplastic dreptul inimii (SHDI) levo-Transpunerea a arterelor mare (l-TAM) Canalul arterial (CA) Atrezie pulmonar Stenoz pulmonar tetralogie Fallot (TOF) pentralogy de Chantrall dextro-Transpunerea a arterelor mari (d-TGA) Atrezie Tricuspid Defect septal ventricular (DSV) Bicuspid valva aortica Stenoz mitral Sindromul Iatagan(SI) Aceasta este o list incomplet, care nu pot fi niciodat n msur s ndeplineasc anumite standarde de finalizare. ntreruperea arcului aortic (AA) Uneori CDD nu se mbuntete cu nici un tratament . Alteori defectul este att de mici i nu necesit tratament. De cele mai multe ori CDD este grav i necesit intervenii chirurgicale i / sau medicamente. Medicamentaia include diuretice, care ajut copilul n eliminarea de ap, sruri, i digoxin i n consolidarea contractiilor inimii. Acest lucru incetinete btile inimii i elimin o cantitate de lichid din tesuturi. Unele defecte necesit proceduri chirurgicale pentru a repara ct mai mult posibil pentru a restabili circulatia reveni la normal. n unele cazuri, mai multe intervenii chirurgicale sunt necesare pentru a fi efectuate pentru a ajuta la echilibrarea circulaiei. Cardiologia ofer acum pacienilor alternative minim invazive pentru intervenia chirurgical.

Boli nutriionale

Ischemice (sau non-ischemice) cardiomiopatiiUtilizate frecvent

termenul "cardiopatia ischemica,", referindu-se la ischemie miocardic i infarct, nu este susinut de schemele curente ale clasificrii cardiomiopatiilor. Cardiopatia ischemic este o slbiciune n muchiul inimii din cauza unor lipsei de oxigen necesar, pentru miocardul cu boal coronarian fiind cea mai frecvent cauz. Anemia i de apneea n somn sunt condiii destul de comune care pot contribui la miocard ischemiei i hipertiroidie poate provoca o "relativ "ischemie secundar la insuficien cardiac de ieire de mare. Persoanele cu cardiomiopatie ischemic de obicei au o istorie de infarct miocardic acut (atac de cord), dei ischemie mult timp n urm poate provoca leziuni suficient pentru a miocardului pentru precipitarea o cardiomiopatie semnificativ clinic chiar i n absena de infarct miocardic. ntr-o prezentare tipic, zona a inimii afectate de un infarct miocardic va deveni iniial necrotice n care se moare, i va fi apoi nlocuit cu cicatrici miocardic (fibroz). Acest tesut fibroase este akinetic; este musculare nu mai este i nu poate s contribuie la funcia inimii ca o pomp. Dac regiunea akinetic a inimii este substanial de ajuns, partea afectat a inimii (adic partea stnga sau la dreapta) va intra n eec, iar acest eec este rezultatul funcionale ale unui cardiopatia ischemica. La unele persoane , stress-ul emoional sever poate duce la "cardiomiopatie takotsubo", o cardiomiopatie specifice, care are o etiologie special. Cardiomiopatiile intrinseci: O cardiomiopatie intrinsec este definit ca o slbiciune muscular a inimii, care nu se datoreaz unei cauze etxerne. Aceast definiie a fost folosit pentru a clasifica cardiomiopatia anterior idiopatic, cu toate c anumite cauze externe au fost identificate, deoarece pentru multi. De exemplu, alcoolism a fost identificat ca fiind un motiv de unele forme de cardiomiopatie dilatate. Multe cardiomiopatii intrinseci au acum cauze externe identificabile, inclusiv droguri i de alcool ,de toxicitate, anumite infecii (inclusiv Hepatita C), precum i diverse genetice i idiopatic (adic, necunoscut) cauze. Cardiomiopatiile intrinseci sunt n general clasificate n patru tipuri, dar sunt tipuri suplimentare, de asemenea, recunoscute: Cardiomiopatie dilatat (CMD), forma cea mai comun, precum i una dintre indicaiile de conducere pentru transplant de inima. n CMD inima (n special ventriculul stng) este extins, precum i funcia de pompare este diminuat. Aproximativ 40% din cazuri sunt familiale, dar genetica sunt prost neleas n comparaie cu HCM. n unele cazuri, se manifest ca cardiomiopatie peripartum, precum i n alte cazuri, poate fi asociat cu alcoolism. Cardiomiopatie hipertrofic (CMH sau CMHO), o tulburare genetic cauzat de mutaii diferite n genele codare proteine sarcomeric. n HCM

muchiului cardiac este ngroat, care poate bloca fluxul de snge i de a preveni inima de la funcionarea corect. Cardiomiopatiile Aritimice ale ventriculului drept (CAVD), rezult dintr-un perturbare electric a inimii, n care muchiului inimii se nlocuiete cu esut cicatricial fibros. Ventriculului drept este, n general, cea mai afectat. Cardiomiopatie restrictiv (CMR) este o cardiomiopatie mai puin frecvent. Pereii ventriculelor sunt rigizi, dar nu poate fi ngroai, i s reziste umplere normal a inimii cu snge. O form rar de cardiomiopatie restrictiv este cardiomiopatie obliterant, vzut n sindrom hipereozinofilic. n acest tip de cardiomiopatie:, miocard n apices din ventricule stnga i din dreapta devine ngroat i fibroase, determinnd o scdere a volumului de ventricule i o de tipul de cardiomiopatie restrictive. Cardiomiopatie noncompactiv a fost recunoscut drept un tip separat din anii 1980. Termenul se refer la un cardiomiopatie n cazul n care peretele din stnga ventriculului nu a reuit s creasc n mod corespunztor de la natere i are un aspect spongios cnd sunt vizualizate n timpul unei ecocardiografie. Simptomele si semnele pot s mimeze cele de la aproape orice form de boli de inima. Durere toracic este comun. Miocardit uoar sau de cardiomiopatie este frecvent asimptomatic; cazurile severe sunt asociate cu insuficien cardiac, aritmii, i embolizarea sistemice. Manifestri ale bolii subiacente (de exemplu, boala Chagas ') pot fi proeminent. Majoritatea pacienilor cu biopsie-miocardit dovedit a raporta o prodrome recent virale precedent simptome cardiovasculare. Modificri ECG sunt adesea prezente, dei modificrile sunt frecvent nespecifice. O caracteristic model de hipertrofie ventricular stng pot fi prezente. Undele opuse unui T sau plate sunt cele mai comune, de multe ori cu joas tensiune QRS complexe. Defecte conductei intraventriculare i ramurile strnse, n special n stnga pachet bloc de ramur, sunt, de asemenea, comune. O ecocardiogram este util pentru a detecta anomalii de perete sau o micare efuziune pericardic. Radiografiile toracice pot fi normale sau pot arata dovezi de insuficien cardiac congestiv, cu edem pulmonar sau cardiomegalie. Tratamentul depinde de tipul de cardiomiopatie, dar pot include medicaie, implantate stimulatoare cardiace, defibrilatoare, sau ventriculare asista dispozitive (LVADs), sau ablaie. Scopul tratamentului este de multe ori symptom relief, iar unii pacieni pot solicita n cele din urm un transplant de inim. Tratamentul de cardiomiopatie (i a altor boli de inim), folosind metode alternative, cum ar fi terapia cu celule stem este disponibil n comer, dar nu este susinut de dovezi convingtoare. Cazuri celebre:

n 1966, adugarea de compui de cobalt a stabiliza spuma de bere n Canada, a condus la cardiomiopatie, care a ajuns s fie cunoscut sub numele de cardiomiopatia butororilor de bere. Dave Williams a Drowning Pool au murit de cardiomiopatie, n 2002. Dr. Robert Atkins, inventator al "Dietei Atkins" a suferit de cardiomiopatie, n ani nainte de moartea sa, de la o cdere. Alexei Cherepanov, 19 ani, juctor profesionist de hochei pe ghea, a murit de cardiomiopatie n timpul unui joc de hochei pe ghea, n 2008. Andy Hallett, un actor de 33 ani vechi din serialul de televiziune Angel, a murit de insuficien cardiac congestiv, n 2009, a adus pe de o cardiomiopatie de la o infecie dinte cinci ani mai devreme. James Michael Hegstrand alias Road Warrior Hawk un wrestler american. Slash, chitaristul de Roses Guns N, cardiomiopatie a supravieuit. Reggie Lewis, cpitan i All-Star a Boston Celtics, a murit de cardiomiopatie hipertrofica, la vrsta de 27. Marc-Vivien Foe, Camerun internaionale & West Ham United fotbalul profesionist (fotbal) player, sa prbuit i a murit de cardiomiopatie hipertrofic obstructiv (HOCM), n vrst de 28 n timpul unui meci Cupa Confederaiilor FIFA la 26 iunie 2003. Cuttino Mobley, un juctor retras NBA care a trecut a jucat pentru LA Clippers, a fost forat s se retrag dup ce a fost diagnosticat cu cardiomiopatie hipertrofica la sfritul anului 2008. Hank Gathers, un star de baschet de colegiu recruta care a jucat pentru Loyola Marymount University, sa prbuit n timpul unui drum liber arunca tentativ mpotriva UCSB i mai trziu din nou mpotriva Universitatea din Portland. A doua oar, el nu sa ridicat i a fost declarat mort la sosire. Nick Carter de Backstreet Boys a fost diagnosticat cu cardiomiopatie dupa ce a suferit dureri n piept. Katie Gallagher, care a introdus al doilea pe reality show TV Survivor: Palau, a fost diagnosticat cu cardiomiopatie virale de mai muli ani mai trziu. Jonathan Amazing a fost diagnosticat cu "o stare grav de inim", n martie 2007. Site-ul interpretului identificat condiia ca cardiomiopatie i a continuat s afirme c, din cauza unei combinaii de pierderea in greutate si diluanti de snge, el a fost de a face bine i nu intenioneaz s se pensioneze. Cardiomiopatie hipertensiv Simptome: Oboseal Puls neregulat Umflarea picioarelor Creterea n greutate Greaa Dificulti de respiraie Dificultatea de dormit apartament n pat Balonare O mai mare nevoie de a urina pe timp de noapte Condiii (complicaii poteniale)

Hipertrofie ventricular stng Boal coronarian de inim Insuficiena cardiac congestiv Cardiomiopatie hipertensiv Cardiomiopatia valvular Cardiomiopatie inflamatorie Cardiomiopatie secundar unei boli sistemice metabolice Cardiomiopatie alcoolic Cardiomiopatia alcoolic este o boal cronic n care abuzul de alcool duce la insuficien cardiac. Cardiomiopatia alcoolic este un tip de cardiomiopatie dilatat. Datorit efectelor direct toxice ale alcoolului asupra muchiului cardiac, inima nu este n msur de a pompa snge n mod eficient, care duce la insuficien cardiac. Ea poate afecta alte pri ale corpului n cazul n care este de insuficien cardiac sever. Acesta este cel mai frecvent la brbaii cu vrste cuprinse ntre 35-50. Simptomele prezentate de apariia de cardiomiopatie alcoolice sunt rezultatul a inimii i de faptul c nu apar de obicei dup ce boala a progresat la un stadiu avansat. Prin urmare, simptomele au multe n comun cu alte forme de cardiomiopatie. Aceste simptome pot include: Glezne, picioare i umflarea lor n ansamblu umflarea Pierderea poftei de mncare Respiraie dificil, n special de activitate Dificulti de respiraie n acelai timp n poziie culcat Oboseal, slbiciune, lein Vigilen sczut sau de concentrare Scderea urinrii (oligurie) Necesitatea de a urina noaptea (nicturie) Palpitaii Puls neregulat sau rapid Diagnostic: sunete anormale ale inimii, murmurele, EKG anomalii, i inima extins pe piept cu raze X, poate duce la diagnostic. Anomalii Ecocardiografie i cateterism cardiac sau angiografia pentru a exclude blocajele arterei coronare, mpreun cu o istorie de abuz de alcool poate confirma diagnosticul. Tratamentul pentru cardiomiopatie alcoolic implic modificri stilul de via, inclusiv abstinena complet de la consumul de alcool, o diet srac n sodiu, i restricie de lichide, precum i medicamente. Medicamente pot include inhibitori ai ECA, beta-blocante, diuretice i care sunt utilizate n mod curent cu alte forme de cardiomiopatie pentru a reduce tulpina de pe inim. Persoanele cu insuficien cardiac congestiv pot fi luate n considerare pentru introducerea chirurgicale a unui ICD sau a unui stimulator cardiac care permite mbuntirea funciei cardiace. n cazurile n care insuficien cardiac este

ireversibil i agravarea, transplant de inim pot fi luate n considerare. Tratamentul va mpiedica, eventual, n centrul de la deteriorarea n continuare, dar este puin probabil s inverseze funcia de redus, care a avut loc deja. Cardiomiopatie diabetic Dintre cauzele care duc la disfuncie cardiac, diabet zaharat este cea mai rspndit. ntr-adevr, acesta este cel mai important factor de risc pentru boli coronariene i diabetici de peste 30% n Statele Unitesunt diagnosticai cu boli de inima. n plus, dou treimi din diabetici vor muri n cele din urm de un fel de boli cardiovasculare. n afar de boli nav de mari i ateroscleroza accelerat, care este foarte comun n diabet, cardiomiopatie diabetic (DCM) este o condiie clinic diagnosticat atunci cnd se dezvolt disfuncie ventricular la pacienii cu diabet zaharat, n absena unor aterosclerozei coronariene i hypertension.DCM pot fi caracterizate de vedere funcional de ventricular dilatare, hipertrofia myocyte, fibroz interstiial proeminente i a sczut sau conservate n funcie a tensiunii arteriale sistolice n prezena unui disfuncie diastolic. Semne & Simptome: O particularitate a CMD este faza lung latent, n care boala progreseaza, dar este complet asimptomatic. n cele mai multe cazuri, DCM este detectat cu hipertensiune concomitente sau boal arterial coronarian. Unul dintre primele semne este uoar disfuncie ventricular stng diastolice, cu un efect redus asupra umplere ventriculare. De asemenea, pacientul cu diabet zaharat pot s prezinte semne subtile ale CMD legate de respectarea ventriculului stng a sczut stnga sau hipertrofie ventricular stng sau o combinaie a ambelor. Un proeminent "un val" poate fi, de asemenea, remarcat, n puls venos jugular, i impulsul cardiace apical poate fi hiperactiv sau susinute n ntreaga systole. Dup elaborarea de disfuncie a tensiunii arteriale sistolice, dilatarea ventricular stng i insuficien cardiac simptomatic, presiunea jugular venoasa poate deveni crescute, impulsul apical ar fi strmutate n jos i la stnga. A tensiunii arteriale sistolice murmur mitral nu este mai puin frecvent n aceste cazuri. Aceste modificri sunt nsoite de o varietate de modificri electrocardiografice, care pot fi asociate cu DCM la 60% dintre pacieni fr boal cardiac structurale, cu toate c de obicei, nu n faza de nceput asimptomatice. Mai trziu, n progresie, o prelungirea intervalului QT poate indica de fibroz. Avnd n vedere c definiia lui DCM exclude ateroscleroza concomitente sau hipertensiune arterial, nu exist modificri n perfuzie sau n atrial niveluri de peptid natriuretic pn n stadii foarte trzie a bolii, atunci cnd hipertrofia i fibroza deveni foarte pronunat. Fiziopatologie:

Cu toate c a fost evident pentru o lung perioad de timp pe care observate la complicaiile diabetului zaharat sunt legate de hiperglicemie asociate la aceasta, mai muli factori au fost implicate n patogeneza bolii. Etiologie, patru cauze principale sunt responsabile pentru dezvoltarea insuficienei cardiace la CMD: microangiopatie i conexe disfuncii endoteliale, neuropatie vegetativ, alterrile metabolice, care includ utilizarea anormale de glucoz i de oxidare a crescut de acizi grai, generarea i acumularea de radicali liberi, i alterri n homeostaziei Ion , n special tranzitorii de calciu. Microangiopatie: Microangiopatia poate fi caracterizat ca fibroza subendotelial i endotelial n microvasculatura coronar a inimii. Aceast disfuncie endotelial duce la afectarea rezervei de snge miocardic fluxul ca mijloc de prob prin ecocardiografie . Aproximativ 50% din diabetici cu DCM, exist dovezi pentru microangiopatie patologice, cum ar fi subfibroza endoteliale i endoteliale, fa de numai 21% de non-diabetice insuficien cardiac pacieni . De-a lungul anilor, mai multe ipoteze au fost postulat pentru a explica disfuncii endoteliale observate n diabetul zaharat. S-a emis ipoteza c hiperglicemie extracelular conduce la o hiperglicemie intracelulare n celule n imposibilitatea de a reglementa asimilarea lor de glucoz, de cele mai multe n principal, celulele endoteliale. ntr-adevr, n timp ce hepatocite myocytes i dispun de mecanisme care s le permit s interiorizeze transportator lor de glucoz, celulele endoteliale nu posed aceast capacitate. Consecinele de concentrare a crescut de glucoz intracelulare sunt, de patru ori toate rezult din creterea concentraiei de intermediari glycolytic n amonte de rata de-limitarea glyceraldehyde-3-fosfat de reacie, care este inhibat de mecanisme activat de a crescut formarea radicalilor liberi, comun n diabet zaharat . Patru ci, enumerate mai jos, toate explica o parte a complicaiilor diabetice. n primul rnd, acesta a fost raportat pe larg ncepnd cu anii 1960 c hiperglicemie cauzeaz o cretere a fluxului prin reductazei aldose i calea poliol. Activitatea sporit a enzimei de detoxifiere aldoze reductaz duce la o epuizare a NADH cofactor esenial, prin urmare, perturba procesele de celul cruciale. Al doilea rnd, creterea 6 fructoz-fosfat, o glicoliz intermediar, va duce la creterea fluxului prin intermediul cii hexosamine. Acest lucru produce N-acetil glucozamina care poate aduga privind reziduurile de serina i treonina i alter ci de semnalizare, precum i cauza inducie patologice de factori de transcriptie a anumitor . Treilea rnd, hiperglicemie determin o cretere a diacylglycerol care este, de asemenea, un activator al kinazei proteine C (PKC) de semnalizare cale. Inducerea PKC cauze efecte duntoare multiple, inclusiv, dar nu se limiteaz la anomalii ale fluxului de snge, ocluzie capilar i pro-inflamatorii expresia genelor. n cele din urm, glucoz, precum i a altor produse intermediare, cum ar fi fructoz i glyceraldehyde-3-fosfat, cnd sunt prezente n concentraii

mari, de a promova formarea de produse finite glicozilare avansate (vrstele). Acestea, la rndul lor, poate traversa ireversibil se leag de proteine i cauza agregatele intracelulare, care nu pot fi degradate de proteaze i, prin urmare, s modifice intracelulare de semnalizare. De asemenea, vrstele pot fi exportate n spaiul intercelular n cazul n care pot receptori obligati AGE (Rage). Aceast vrst / interaciune RAGE activeaz ci inflamatorii cum ar fi NFB, n celulele gazd ntr-o manier autocrine, sau n macrofagele ntr-o manier paracrine. De activare Neutrofile poate duce, de asemenea, la DNA (P) H oxidaza producia de radicali liberi mai mult deteriorarea celulelor din jur. n sfrit, a exportat produse de glicozilare proteine obligati extracelular i modifice matricea, interaciunile celul-matrice i de a promova fibroz. O surs major de rigiditate a crescut miocardic este crosslinking ntre vrstele i colagen. De fapt, un semn distinctiv al diabetului zaharat necontrolat este glycated produse n ser i poate fi utilizat ca un marker pentru microangiopatie diabetic. Anormalitile metabolice ale miocardului Eventual una dintre primele diferene de observat la inimile cu diabet zaharat au fost derajamentele metabolice. ntr-adevr, chiar i n anii 1950, s-a recunoscut c micologia cardiac de la un pacient cu diabet zaharat a avut o anormal, energie-funcia ineficiente metabolice, cu aproape nici o oxidare carbohidrai . Schimbrile observate la DCM nu sunt diferite de cele ale ischemie, i ar putea explica de ce diabetici sunt mai susceptibile la daune ischemica, i nu sunt uor de testat. n plus, diabet zaharat conduce la o hiperglicemie persistent foarte multe ori nsoit de un hiperlipidemia. Acest disponibilitatea modific substrat la inima i cu siguran afecteaz metabolismul acestuia. n condiii normale, acizi grai sunt substrat preferat n miocard adulte, furnizarea de pn la 70% din totalul ATP. Ele sunt oxidate n matricea mitocondrial de procesul de acid gras-oxidare, n timp ce piruvatului derivat din glucoz, glicogen, a lactatului i a piruvatului exogene este oxidat de complexe dehidrogenazei piruvatului, localizat n membrana interioar mitocondriale. Substrat alegere n inima pentru aduli este reglementat n principal, de disponibilitatea, cererea de energie i aportul de oxigen. Prin urmare, nu este surprinztor faptul c modificrile sunt prezente n diabet i s contribuie din plin la patogeneza sale. Cardiomicologiile, spre deosebire de celulele endoteliale, au capacitatea de a reglementa asimilarea lor de glucoz. Astfel, ele sunt n mare parte cruat de la complicaii asociate cu hiperglicemie c ciuma celulelor endoteliale. n scopul de a se proteja de hiperglicemie extracelulare, celule cardiace pot interiorizeze insulin lor de-transportor dependente de glucoz, GLUT4. Cnd uita la utilizarea de carbohidrai de miocard, nu inimile diabetici numai arat o scdere a utilizrii de glucoz, dar i o scdere foarte pronunat n utilizarea

lactatului, ntr-o msur mai mare dect utilizarea glucozei. Mecanisme sunt neclare, dar nu sunt legate de lactat de transport sau de expresie lactat dehidrogenaz. Mai mult, datorit o asimilare cu deficit de hidrai de carbon, miocard cu diabet zaharat arat creteri n piscina de glicogen intracelulare, posibil prin sinteza crescut sau au sczut glicogenolizei. Cu toate acestea, ca un dezavantaj n acest scderea captrii glucozei, cardiomyocytes se confrunt cu o rat redus de oxidare glucoz i o a crescut dramatic de acizi grai-oxidare la aproape 100% din producia ATP. Acest lucru se traduce ntr-o cretere dramatic a transportatorului de acizi grai, n special CD36, care este postulat de a avea un rol important n etiologia de boal cardiac. Interesant, se pare c scderea de oxidare carbohidrat precede apariia de hiperglicemie, n diabetul zaharat tip II. Este, probabil, ca urmare a -oxidarea a crescut ca urmare a hiperlipidemia i de insulin modificat de semnalizare. Rata de absorbie a lipidelor, spre deosebire de cel al glucozei, care nu este reglementat de un hormon. Prin urmare, a crescut lipide circulante va crete absorbia i, prin urmare, de acid gras de oxidare. Aceasta, la rndul su, crete concentraia de citrat n celul, un inhibitor potent al phosphofructokinase foarte, rata de primul-pas de limitare a glycolysis. n cazul n care rata de absorbie este mai mare dect rata de oxidare, acizi grai sunt shuttled vedere calea de sinteza trigliceridelor. Creterea magazine de trigliceride a preveni lipotoxicity, dar scderea funciei cardiace. De ce sunt toate aceste modificri n detrimentul inima? Dovezi emergente sprijin conceptul c modificrile n metabolizarea contribuie la disfuncia cardiac contractil. La modelele animale, insuficien contractil ncepe ca o disfuncie diastolice, i progreseaz, ocazional, pentru a disfuncie a tensiunii arteriale sistolice n cele din urm duce la insuficien cardiac. Normalizare a metabolismului energetic n aceste inimi a inversat contractilitii depreciat. n timpul diabet zaharat, remodelarea metabolice precede cardiomiopatie i este valabil la ipoteza ca aceste schimbri pot contribui la disfuncie cardiac. ntradevr, atunci cnd se trateaz pe modele animale cu Modulatoare metabolice la o vrst fraged, nainte de orice semn de cardiomiopatie, mbuntiri ale funciei cardiace pot fi observate. Astfel, este evident c derangements metabolice observate la DCM nu numai precede patologia, dar, de asemenea, contribuie foarte mult la dezvoltarea acestuia. Neuropatie autonom: n timp ce inima nu poate funciona fr ajutor din partea sistemului nervos, este foarte innervated autonome cu nervii, inima bate de reglementare n conformitate cu cererea ntr-un mod rapid, nainte de eliberarea hormonale. Innervations autonom de miocard n DCM sunt modificate i s contribuie la disfuncie miocardic. Spre deosebire de

creierul, sistemul nervos periferic nu beneficiaz de o barier n calea protejnd-o de la nivelurile circulante de glucoz. La fel ca celulele endoteliale, celulele nervoase nu se pot reglementa glucoz lor de absorbie i sufer acelai tip de daune-interese enumerate mai sus. Prin urmare, inima cu diabet zaharat de denervation arata clar ca patologia progreseaz. Acest denervation coreleaz cu dovezi ecocardiografic de disfuncie diastolic i rezultate ntr-un declin de supravieuire la pacienii cu diabet zaharat de la 85% la 44%. Alte cauze de ischemie denervation sunt de boli microvasculare i, astfel, apar ca urmare a dezvoltrii de microangiopatie. Homeostazia Ion Altered Spre deosebire de cele mai multe alte tipuri de celule, inima are n mod constant i se schimb rapid statutul de ionice, cu cureni de ioni diverse merge n afar din celul n timpul fiecrui ciclu de btaie. Mai important, de calciu este un juctor major al evenimentelor cardiace electromecanice, metabolismului energetic i funcia contractil. Ea se mut n ntreaga sarcolemma, reticulului sarcoplasmic i membranele mitocondriale, prin diferite canale specifice de ctre organelle de transport activ, precum i difuzie pasiv. Aproximativ 30-40% din producia ATP, a unui cardiomyocyte este utilizat n principal de ctre CA2 reticulului sarcoplasmic +-ATPase (SERICA) i pompe de ioni altele. Astfel, este evident c orice modificare a homeostaziei va avea consecine grave asupra funciei inimii i, eventual, integritatea i structura. n DCM, aceste modificri s-au constatat de la anilor '80. ntr-adevr, studiile indic o scdere n capacitatea celulelor de a elimina CA2 + prin intermediul Na +-CA2 + schimb i CA2 +-sistemelor de pompare n sarcolemma inimilor obolan diabetice. Mai recent, scderea activitii SERCA sa dovedit a fi o contribuie major la dezvoltarea de disfuncie cardiac n diabetul zaharat i au sczut expresie a canalului a fost de asemenea raportate. Aceste diferene sunt parial explicat de calciu, modificat de semnalizare la nivelul receptorului ryanodine, o autoritate de reglementare cheie al SERICA , precum i creterea n phospholamban observate n inimile cu diabet zaharat. Iniial, aceste anomalii s-au gndit s fie asociat cu suprancrcare de calciu intracelular; cu toate acestea, dovezi ulterioare da vina modificat [CA2 +] tranzitorii i cu nemodificat concentraii bazale. Aceste modificri nu sunt limitate la curenti de calciu. Increases in intracellular sodium concentrations also play a causative role of ischemic damage sensitivity in diabetes and are related to a decrease in the Na+-H+ pump activity due to hyperglycemia. Furthermore, there is a decrease in a Na+-K+ ATPase subunit expression, correlating with a decrease in expression of the Na+-Ca2+ exchanger. More importantly, several potassium current abnormalities are observed. DCM causes alterations in transcription and surface expression of potassium channel

proteins, which are theorized to be under the control of insulin-signaling cascade. Indeed, abnormalities in K+ can be restored in vitro following incubation with insulin. Further, altered duration of the action potential, known to be increased in DCM, was shown to result mainly from a decreased K+ transmembrane permeability Tratament: Terapiile convenionale n prezent, nu exist un singur tratament clinic eficient pentru cardiomiopatie diabetic. Centre de tratament n jurul intensa de control glicemic prin dieta, hypoglycemics orale i n mod frecvent de insulin i de gestionare a simptomelor de insuficien cardiac. Exist o corelaie clar ntre creterea glicemiei i riscul de a dezvolta diabet zaharat de cardiomiopatie, prin urmare, pstrarea concentraiile de glucoz n controlate, aa cum posibil este primordial. Tiazolidinedionele nu sunt recomandate, la pacienii cu NYHA clasa III sau IV, insuficien cardiac secundar la retenia de fluide. Ca i n cele mai multe alte boli de inim, enzimei de conversie a angiotensinei (ECA) poate fi, de asemenea, administrat. O analiz a majore studiile clinice arat c pacienii diabetici cu insuficien cardiac beneficia de o astfel de terapie ntr-o msur similar cu cea non-diabetici [48]. n mod similar, beta blocante sunt, de asemenea comune n tratamentul insuficienei cardiace concomitent cu inhibitori ai ECA. Din pcate, utilizarea lor la pacienii cu diabet zaharat este mai sensibil din cauza efectul lor negativ asupra glicemiei. Cu toate acestea, o blocante, n standuri special afar, carvedilol. Datorit proprietilor sale metabolice modulant, sa dovedit a fi benefic n combinaie cu inhibarea ECA, fara a afecta glicemiei. Interveniile nutritive Metale de tranziie Avnd n vedere c multe mecanisme implicate n patogeneza DCM au o baz n chimie radical liber, i c multe dintre aprare antioxidant al celulelor se bazeaz pe urm metale, acesta este vrednic s ia n considerare suplimentarea de anumite metale ca parte a unei cuprinztoare potenial de tratament. ntr-adevr, la obolani, suplimentarea cu seleniu a avut un posibil efect benefic asupra activitilor electrice ale inimii cu diabet zaharat, posibil datorit restaurare a diminuat K + cureni i parial legate de o restaurare a ciclului celular de glutation redox . Mai mult, se tie c deficitul de zinc este un factor de risc pentru cardiomiopatie. ntr-adevr, studiile au artat un risc crescut de a dezvolta diabet zaharat de corelare cu scderea concentraiilor de Zn, precum i chelators Zn induce diabet zaharat, n unele specii de mamifere. n timp ce potenialul de Zn de mbuntire a simptomelor DCM nu a fost nc s fie evaluate, avantajele sale au fost abordate ntr-o alt complicaie a diabetului zaharat la pacienii, neuropatia periferic unde a fost indicat pentru a ajuta la controlul glicemiei i a atenua unele simptome. n cele din urm, un studiu clinic robust, cu toate c pe termen scurt, a artat c

suplimentarea oral de magneziu poate fi eficace n reducerea nivelului glucozei plasmatice jeun i creterea HDL colesterol la pacienii cu diabet zaharat de tip 2, cu toate beneficiile pe termen lung i sigurana tratamentului cu magneziu pe de control glicemic urmeaz s fie stabilite. Tiamina O alt intervenie nutriionale ar fi suplimentarea tiamin. Aa cum sa explicat mai sus, endoteliale, precum i disfuncii nervilor periferici sunt cauzate de incapacitatea pentru aceste tipuri de celule de a reglementa asimilarea lor de glucoz. Aceasta duce la o cretere a produselor intermediare, n amonte de inhibat GAPDH. Ea a fost recent artat c suplimentarea de nalt tiamin activeaz o enzim, transketolase, care metabolizeaza glyceraldehyde acumularea-3-fosfat. Aceasta, la rndul su, previne complicaiile asociate cu hiperglicemie. Cu toate c nici un studiu clinic a fost efectuat pentru a corobora aceste rezultate la pacieni, o biodisponibilitate foarte versiune a tiaminei a fost dat la cini cu diabet zaharat i a fost demonstrat pentru a preveni retinopatie, o complicaie a diabetului legate de disfunctii endoteliale. In vitro, tiamin a fost demonstrat, de asemenea, pentru a diminua producia de vrst, de activitate PKC, inflamaie i Flux, prin calea hexosamine, patru cauze de disfuncie endoteliale. Taurin Taurina este un acid amino sulfuric semi-esential provenit de la metabolismul metionina i cisteina. Studii recente au oferit un rol de taurina n dezvoltarea ftului i n diminuarea efectelor diabetului ntr-o mama cu diabet zaharat i a descendenilor si. n plus, datele experimentale sugereaz faptul c taurina ar putea avea efecte benefice n diabetul zaharat. Cu toate acestea, studiile clinice au fost prea mici si prea scurt pentru a avea vreo importan real i efectele sale asupra inimii nu au fost documentate.

Cardiomiopatie restrictiv

Cardiomiopatie restrictive (RCM) este o form de cardiomiopatie, n care pereii sunt rigide, iar inima este restricionat de la ntindere i umplerea cu snge n mod adecvat. Acesta este cel de cardiomiopatie comune. Prezentare: Ritmicitate i contractilitii inimii poate fi normale, dar zidurile rigid a camerelor inimii (atrii i ventriculi), pstrai-le n mod adecvat de la umplere, reducerea preload i la sfritul volumului-diastolice. Deci, fluxul de snge este redus, precum i de snge care ar intra n mod normal, inima este susinut n sistemul circulator. n timp, pacienii cu cardiomiopatie restrictiv dezvolt disfuncie diastolice i n cele din urm insuficien cardiac. Cauzele Este posibil s se mpart n cauzele primare i secundare.

Primare Sindromul Lffler fibroelastosis endocardial Secundar infiltrativ amiloidoz cardiac haemochromatosis sarcoidoz interstiial fibroz postradiation Alte cauze includ sclerodermia, sindromul Churg-Strauss, cystinosis, limfom, boala Gaucher, hemocromatoza, boala Fabry lui, pseudoxanthoma elasticum, sindrom hipereozinofilic, carcinoide, sindromul Noonan lui, artrita reactiv, i sindromul Werner lui. Tratament Terapie pentru cardiomiopatie restrictiv este limitat. Diureticele pot ajuta la ameliorarea simptomelor. Insuficien cardiac rezult din cardiomiopatie restrictive, de obicei, n cele din urm va trebui s fie tratat prin transplant cardiac.

Ateroscleroza
Clasificarea i resurse extere Schimbri n disfuncii endoteliului in ateroscleroza (comentarii nota text despre eroare de geometrie) Ateroscleroza (de asemenea cunoscute ca Arteriosclerotic vasculare Afectiune sau ASVD) este starea n care se ingroasa un perete al unei artere, ca rezultat al acumulrii de materii grase, cum ar fi colesterolul. Acesta este un sindrom care afecteaz vasele de snge arterial, un rspuns cronice inflamatorii n pereii arterelor, n mare parte datorit la acumularea de macrofage celule albe din snge i promovat de Lowlipoproteine cu densitate (proteine plasmatice care transporta colesterol i trigliceride), fr ndeprtarea adecvat grsimilor i colesterolului din macrofage prin funcionale lipoproteine cu densitate mare (HDL), (a se vedea apoA-1 Milano). Acesta este de obicei menionat drept o intarire sau blan de artere. Aceasta este cauzat de formarea de plci n cadrul mai multor artere. Placa atheromatous este mprit n trei componente distincte:

Atheroma ( "forfetare de terci", de la , athera, ncasa n greac,), care este acumularea nodular dintr-un material moale, cu fulgii, de culoare galben de la centrul de plci mari, compus din cel mai apropiat macrofagelor lumen al arterei La baza domenii de cristale de colesterol Calcifiere la baza exterioar a mai n vrst / leziuni mai avansate. Urmtorii termeni sunt similare, dar distincte, n ambele ortografie i sensul, i poate fi uor confundat: arteriosclerozei, arteriolosclerosis, i ateroscleroza. Arterelor Arterioscleroza este un termen general care descrie orice clire (i pierderea elasticitii), de mediu sau a arterelor mari (de la ARTERIA greac, sensul artera, i scleroz, sensul ntrire); arteriolosclerosis este orice clire (i pierderea elasticitii) din arteriolelor (mici ); Ateroscleroza este o rigidizarea o arter n mod special din cauza unei plci atheromatous. atherogenic Termenul este utilizat pentru substane sau procese care cauzeaz ateroscleroza. Ateroscleroza, dei de obicei asimptomatic timp de decenii, n cele din urm produce dou probleme principale: n primul rnd, plci aterosclerozatice, dei mult timp compensate de extindere a arterelor (a se vedea IMT), n cele din urm duce la rupturile plci i de cheaguri n interiorul lumenul arterei peste rupe. Cheaguri de vindeca i, de obicei termale, dar lasa in urma stenoza (ngustarea) a arterei (att la nivel local i, n mai mici ramuri din aval), sau, mai ru, nchiderea complet, i, prin urmare, o cantitate insuficient de snge la esuturi i organe se hraneste. n al doilea rnd, n cazul n care procesul de artera compensatoare de extindere este excesiv, atunci o rezultate net de anevrism. Aceste complicatii ale aterosclerozei avansate sunt cronic, lent progresiv i cumulative. Cel mai frecvent, plci moale brusc rupturi (a se vedea placa vulnerabile), determinnd formarea unei trombilor care va incetini rapid, sau a opri fluxul de snge, ducnd la moartea a esuturilor alimentat de artera n aproximativ 5 minute. Acest eveniment catastrofic se numete un infarct. Unul dintre scenariile cele mai comune recunoscute este numit tromboz coronare ale unei artere coronare, care provoac infarct miocardic (un atac de cord). Chiar i mai ru este acelai proces ntr-o arter la creier, denumit accident vascular cerebral. Un alt scenariu comune n boala foarte avansat este claudicaie de la aprovizionarea cu snge insuficient pentru a picioarelor, de obicei din cauza unei combinaie a celor dou segmente de stenoz i sa anevrismul redus cu cheaguri. Din moment ce Ateroscleroza este un organism-amplu proces de, evenimente similare au loc, de asemenea, n artere la creier, intestine, rinichi, picioare, etc Cauze: Ateroscleroza se dezvolt de la molecule mici: lipoproteine cu densitate (LDL) devenind oxidat (LDL-bou) de radicalii liberi, n special specii reactive de oxigen (ROS). LDL oxidat Atunci cnd vine n contact cu un zid de arter, o serie de reacii apar pentru a repara prejudiciul la

peretele arterei cauzate de LDL oxidat. Molecul LDL este n form de globular cu un miez gol, pentru a transporta colesterolul n ntreg organismul. Colesterol poate muta in sange numai prin a fi transportat de lipoproteine. Sistemul imunitar al organismului raspunde la deteriorarea peretele arterei cauzate de LDL oxidat, prin trimiterea specializate de celule albe din snge (macrofage i T-limfocitele), pentru a absorbi oxidat-LDL celule care formeaz spum de specialitate. Din pcate, aceste celule albe din snge, nu sunt capabile s proceseze oxidat-LDL, precum i n cele din urm s creasc, apoi ruptur, depozitare o cantitate mai mare de colesterol oxidat n peretele arterial. Aceast situaie genereaz mai multe celule albe din snge, care continu ciclul. n cele din urm, artera se inflameaza. Placa colesterol cauze celulele musculare pentru a mri i de a forma o acoperire tare pe zona afectat. Aceasta acoper greu este ceea ce determin o ngustare a arterei, reduce fluxul de snge i crete tensiunea arterial. Unii cercettori cred c ateroscleroza poate fi cauzat de o infectie a celulelor musculare netede vasculare. Pui, de exemplu, dezvoltarea aterosclerozei atunci cnd infectate cu herpesvirusului boala lui Marek. Herpesvirus infecie a arteriale celulele musculare netede a fost demonstrat de a provoca ester cholesteryl (CE) acumulare. Colesterolul este folosit ca substan sau procesele care duc la ateroscleroza. De asemenea, citomegalovirus (CMV), infecia este asociat cu boli cardiovasculare. Simptome Ateroslceroza incepe de obicei in adolescenta timpurie, i este de obicei gsit n cele mai multe artere importante, dar este asimptomatic i nu a fost detectat de cele mai multe metode de diagnostic n timpul vieii. Atheroma n bra, sau mai des, n artere picior, care produce scderea fluxului de snge se numeste boala arterelor periferice ocluziv (PAOD). Conform datelor Statele Unite pentru anul 2004, pentru aproximativ 65% dintre brbai i 47% dintre femei, primul simptom al bolii aterosclerotice cardiovasculare este de atac de cord sau moarte subit de cauz cardiac (moartea n termen de o or de la debutul simptom). Cele mai multe artere perturba fluxul de evenimente au loc n locaii cu lumenul ngustarea mai puin de 50% (~ 20% este stenoz medie). [Cititorul s-ar putea reflecta faptul c ilustraia de mai sus, la fel ca cele mai multe ilustraii de boal arterial, overemphasizes ngustarea Lumen, spre deosebire de compensatorii de extindere diametru extern (cel puin n artere mai mici, de exemplu, artere, inima), tipice ale procesului de ateroscleroza aa cum progreseaza, a se vedea Glagov i proces asteroid, fotografii IVUS la pagina 8, ca exemple pentru o nelegere mai exact. Eroarea relativ geometrie n cadrul ilustrare este comun pentru multe ilustraii n vrst, o eroare de lent, fiind mai frecvent recunoscut n ultimul deceniu.] Cardiace stres de

testare, n mod tradiional, cel mai frecvent efectuate non-invaziva metoda de testare pentru limitarea fluxului de snge, n general, detecteaz lumenul numai ngustarea ~ 75% sau mai mare, desi unii medici susin c metodele de stres nuclear poate detecta ct mai puin de 50%. Aterogeneza Aterogeneza este procesul de dezvoltare a plcilor ateromate. Acesta este caracterizat printr-o remodelare a arterelor care implic acumularea concomitent de substane grase numite placi. O teorie recente sugereaz c, din motive necunoscute, leucocitelor, cum ar fi monocite sau bazofile, ncepe s atace endoteliul a lumenului arterei n muchiul cardiac. Inflamaie a urmat duce la formarea de plci atheromatous n intima Tunica arteriale, o regiune din peretele vasului situat ntre endoteliul i mass-media Tunica. Cea mai mare parte a acestor leziuni este fabricat din excesul de grsime, colagen, si elastina. La nceput, n calitate de placi cresc, doar de perete ngroarea apare fr nici o ngustare, stenoz a arterei de deschidere, numit lumenul; stenoz este un eveniment cu ntrziere, care niciodat nu pot s apar i este adesea rezultatul rupturii placii repetate i rspunsuri vindecare, nu doar procesul de ateroscleroza de la sine. Celular Micrografia unei artere care alimenteaz inima cu ateroslceroz seminificant i marcat cu semnale luminoase. Trizomia lui Masson. Primul pas al aterogenezei este dezvoltarea aa-numitele "urme grase", care sunt sub mici depozite endoteliale ale monocite-derivate macrofage. Conductorul auto documentate primar al acestui proces este oxidat particule de lipoproteine n perete, sub celulele endoteliale, dei superioar concentraii normale sau crescute ale glucozei n snge, de asemenea, joac un rol major, i nu toi factorii sunt pe deplin nelese. Dungile grai poate s apar i s dispar. De joas densitate lipoprotein particule n plasma de snge, atunci cnd acestea invada endoteliul i a devenit oxidat creeaz un risc pentru boli cardiovasculare. Un set complex de reacii biochimice reglementeaz oxidarea LDL, mai ales stimulate de prezena unor enzime, de exemplu LP-radicalii LpA2 i gratuit, n endoteliul sau snge cptueal navei. Daune iniial la snge rezultatele nava de perete ntr-un apel "pentru ajutor", un raspuns inflamator. Monocite (un tip de celule albe din snge), intra in peretele arterei din fluxul sanguin, cu trombocite care ader la zona de insult. Acest lucru poate fi promovat prin inducerea redox de semnalizare de factori, cum ar fi VCAM-1, care a recruta circulant monocite. Monocite diferenia macrofage, care ingera LDL oxidat, ncet se transforma n celule de spum de mare "" - asadescris, din cauza aspectului lor a fost schimbat care rezult din numeroase vezicule citoplasmatice interne i rezult un coninut ridicat de lipide. Sub microscop, leziune acum apare ca o dung grai. Spuma

de celule mor n cele din urm, i n continuare propaga procesului inflamator. Exist, de asemenea, proliferarea musculare netede i a migraiei de la mass-media Tunica intima pentru a rspunde la citokine secretat de deteriorat celulelor endoteliale. Acest lucru ar duce la formarea unei capsule fibroase care acoper cu baleiaj gras. Calcificri i lipide Form intracelular de microcalcificri n termene de celulele vasculare musculare netede ale stratului de nconjurtoare musculare, n special n celulele musculare adiacente ateromate. n timp, dup cum celulele mor, aceasta duce la depozitele de calciu extracelular ntre perete musculare i Partea exterioar a plcilor atheromatous. O form similar de o calcifiere intramural, care prezint imaginea de o faza timpurie a arteriosclerozei, pare a fi indus de o serie de medicamente care au un mecanism antiproliferativ de aciune (Rainer Liedtke 2008). Colesterolul este livrat n peretele vasului de colesterol - cu coninut de lipoproteine cu densitate joas (LDL) particule. Pentru a atrage i de a stimula macrofagelor, colesterol trebuie s fie eliberat din particule LDL i oxidat, un pas cheie n cadrul procesului inflamator n curs de desfurare. Procesul se agraveaz n cazul n care nu exist suficiente lipoproteine de mare densitate (HDL), particula lipoprotein care nltur colesterolului din esuturi i transport napoi la ficat. Celulele spum i plachetele s ncurajeze migraia i proliferarea celulelor musculare netede, care, la rndul su ingera lipide, devenit nlocuiete cu colagen i s transforme n celule spuma de ei nii. Un capac de protecie fibroase n mod normal, forme ntre depozitele grai i garnitur artera (intima). Aceste depozite plafonate grai (numit acum ""), produce enzime care cauzeaza artera pentru a mri n timp. Atta timp ct artera extinde suficient pentru a compensa grosimea suplimentare de atheroma, atunci nu ngustarea ( "stenoz") de deschidere ( "lumen") are loc. Artera devine extins cu un ou-in forma de cruce-seciune, nc cu o deschidere circular. n cazul n care extinderea este dincolo de proporional cu grosimea atheroma, apoi un anevrism este creat. Caracteristici vizibile Aterosclerozei severe de aorta. Specimen autopsie. Dei arterelor de obicei nu sunt studiate la microscop, dou tipuri de plci se pot distinge: Fibro-lipide (Fibro-grai), placa este caracterizat de o acumulare de lipide-celule ncrcat sub intima a arterelor, de obicei fr ngustarea lumenului datorit expansiunii compensatorii a stratului care delimiteaz musculare din peretele arterelor. Sub endoteliul exist un capac "fibros" care acoper atheromatous "de baz" a placii. Nucleul este format din lipide-celule ncrcat (macrofage i celulele musculare netede), cu colesterolul esut crescute de colesterol i de coninutul de ester, fibrin, pretoglicani, colagen, elastina, i resturile celulare. n plci avansate, nucleul central al placii de obicei, conine depozite de colesterol

extracelular (eliberat din celule moarte), care formeaz zonele de cristale de colesterol cu gol, ac-ca clefts. La periferia plci sunt mai mici "spumoase", celule i capilare. Aceste plci de obicei produc cele mai multe daune individuale, atunci cnd ruptura. Placa fibroas este, de asemenea localizat n cadrul intim, n termen de peretele arterei rezultnd ngroarea i extinderea de perete i, uneori, ngustarea plin de couri localizate a lumenului cu unele atrofie a stratului de musculare. Plac fibros conine fibre de colagen (eozinofilic), precipitatii de calciu (hematoxylinophilic) i, rar, lipidelorcelule ncrcat. ntr-adevr, partea muscular a peretelui arterei forme de anevrisme mici, doar suficient de mari pentru a deine atheroma care sunt prezente. Poriunea muscular a peretii arterelor de obicei, rmne puternic, chiar i dup ce acestea au remodeled pentru a compensa placi atheromatous. Cu toate acestea, atheromas n peretele vasului sunt moi i fragile, cu elasticitate mic. Arterele n mod constant extinde i pentru fiecare contract cu bti de inim, adic, puls. n plus, depozitele calcifiere dintre partea exterioar a atheroma i peretele musculare, pe msur ce progreseaz, s conduc la o pierdere de elasticitate i rigidizarea arterelor ca un ntreg. Depozite de calcifiere, dup ce acestea au devenit suficient de avansate, sunt parial vizibile pe tomografie coronarian calculat sau tomografie fascicul de electroni (EBT) ca inele de densitate a crescut radiografice, care formeaz n jurul halouri marginile exterioare ale plcilor atheromatous, n peretele arterial. La CT,> 130 de uniti pe scara Hounsfield (unii susin timp de 90 de uniti) a fost densitate radiografice acceptat ca de obicei, n mod clar, reprezentnd calcifiere esut n termen de artere. Aceste depozite demonstreze fr echivoc a bolii, relativ avansate, chiar dac lumenul arterei este de multe ori nc normal prin ecografie angiografic sau intravasculara. Ruptur i stenoz Dei procesul de boala tinde s fie lent progresiv a lungul deceniilor, de obicei, asimptomatice, pn cnd rmne o atheroma ulcerates ceea ce duce la coagularea sngelui imediate la locul de ulcer atheroma. Acest lucru declaneaz o cascad de evenimente care conduce la coagularea de extindere, care poate bloca rapid lumenul (deschidere) a arterei n sine. Un blocaj complet duce la ischemie de miocardic (cardiac) musculare i daune. Acest proces este infarct miocardic sau "atac de cord." n cazul n atac de cord nu este fatal, organizarea fibroase din cheag n cadrul apare Lumen, acoperind ruptur, dar care produc, de asemenea, stenoza sau nchiderea Lumen, sau n timp i dup rupturi repetate, rezultnd ntr-o stenoz persistente, de obicei localizate sau blocare a

lumenul arterei. Stenoze poate fi lent progresiv, n timp ce placa ulceraii este un eveniment care apare brusc n mod special n atheromas cu diluant / capace de mai slabe fibroase care au devenit "instabile". Rupturile plcii repetat, nu cele rezultate n nchiderea total Lumen, combinate cu patch-cheag de peste ruptur i de reacie de vindecare a stabiliza cheag, este procesul care produce cele mai multe stenoze-a lungul timpului. Domeniile stenotic tind s devin mai stabil, n ciuda vitezele fluxului crescut de la aceste narrowings. Cele mai importante de snge-flow-ul-oprire evenimente au loc la placi mari, care, nainte de ruptur lor, a produs foarte puin n cazul n care nici o stenoza. Din studiile clinice, 20% este stenoz de mediu la plachete, care ulterior ruptur cu rezultate nchiderea complet a arterelor. Cele mai multe evenimente severe clinice nu apar la plachete, care produc stenoza de nalt calitate. Din studiile clinice, doar 14% din atacuri cardiace apar de la nchiderea arterelor de la producerea unui plachete de 75% sau mai mare stenoz nainte de nchidere navei. n cazul n care capacul fibroase de separare un atheroma moale din fluxul sanguin n artera rupe, fragmente de esut sunt expuse i eliberat, i sngele intr atheroma n perete i, uneori, rezultate ntr-o expansiune brusc a dimensiunii atheroma. Fragmente de esuturi sunt foarte cheag de-promovarea, cu coninut de colagen i de factorul tisular, ei activa trombocitelor i a activa sistemul de coagulare. Rezultatul este formarea unui trombilor (cheag de snge) deasupra atheroma, care blocheaz fluxul de snge acut. Cu obstrucie a fluxului de snge, esuturi aval sunt nfometai de oxigen i substane nutritive. n cazul n care acest lucru este miocard (muchiul cardiac), angin pectoral (durere toracic) sau infarct miocardic (atac de cord), se dezvolt. Diagnosticul bolii plcii relatate Microfotografie de perete arteriale cu calcifiata culoare violet () plci aterosclerotice (haematoxillin & eosin pat) Domenii de restrngerea sever, stenoza, detectabile de angiografie, i ntr-o mai mic msur "de stres de testare" au fost mult timp n centrul umane tehnicilor de diagnosticare pentru boli cardiovasculare, n general. Cu toate acestea, aceste metode se concentreze pe depistarea doar restrngerea sever, nu bolii subiacente ateroscleroza. Aa cum sa demonstrat prin studii clinice umane, evenimentele cele mai severe apar in locatii cu plci grele, dar puin sau deloc prezente lumenul ngustarea nainte de evenimente debilitante apar brusc. Ruptur Placii poate duce la ocluzia arterei lumen n termen de secunde pentru a minute, i debilitate potenial permanent i, uneori, brute moarte. Plci care s-au rupt sunt numite placi complicate. Pauzele de lipide matrice prin diferena de colagen subierea i atunci cnd a lipidelor vin n contact cu sngele, coagulare se produce. Dup ruptura de adeziune

de trombocite cauzele cascad coagulare la contactul cu piscina lipide cauznd o trombilor, pentru a forma. Acest lucru trombilor va crete n cele din urm i de cltorie n ntreg organismul. Trombilor va cltori prin artere diferite i venele i, eventual, s devin depus ntr-o zon care se ngusteaz. Odat ce zona este blocat, de snge i de oxigen nu vor fi n msur s furnizeze navelor i va cauza moartea de celule i poate duce la necroz i a otrvirii. Plachete complicate grave poate duce la moartea a esuturilor de organe, provocnd complicaii grave la acest sistem de organe. Mai mare de 75% stenoza lumenului folosit pentru a fi luate n considerare de ctre cardiologi ca nsemn al bolii clinic semnificative deoarece este de obicei doar la acest severitatea ngustarea arterelor inimii mai mare ca episoade recurente de angin pectoral i tulburri de sensibilitate a metodelor de testare de stres sunt vzute. Cu toate acestea, studiile clinice au artat c doar aproximativ 14% din punct de vedere clinic evenimente debilitante s apar n locuri cu acest lucru, sau de gravitatea mai mare a ngustarea. Majoritatea evenimentelor au loc ca urmare a atheroma ruptur plci de la zonele fr a ngustarea suficient pentru a produce orice angin sau stres anomalii de testare. Astfel, din moment ce mai trziu anilor 1990, o atenie mai mare este axat pe placa "vulnerabile". Dei nici o artera n organism poate fi implicai, de obicei, doar reducerea sever sau obstrucie a unor artere, cele care de aprovizionare mai critic-organe importante sunt recunoscute. Obstrucionare a arterelor care furnizeaz rezultat muchiului inimii ntrun atac de cord. Obstrucionare a arterelor care furnizeaz rezultat creierului ntr-un accident vascular cerebral. Aceste evenimente sunt schimba viaa, i, adesea, duce la pierderea ireversibil a funciei, deoarece a pierdut muchiului inimii i celulele creierului nu creasc din nou ntr-o msur semnificativ, de obicei mai puin de 2%. Peste ultimii zeci de ani, alte metode dect angiografia i de stresde testare au fost dezvoltate ca din ce n ce mai bune metode pentru a detecta bolii aterosclerotice nainte de acesta devine simptomatic. Aceste au inclus att (a) metode de detectare anatomice i (b) metode de msurare fiziologic. Exemple de astfel de metode anatomice includ: (1) de calciu coronarian de notare de ctre CT, (2) IMT carotide (grosime intimal mass-media) de msurare prin ultrasunete, i (3) IVUS. Exemple de astfel de metode fiziologice includ: (1) lipoprotein analiza subclas, (2) HbA1c, (3) HS-CRP, i (4) homocisteinei. Exemplu de sindrom metabolic combin att anatomice (diametru abdominale) i fiziologic (a tensiunii arteriale, Valori crescute ale glucozei din snge) metode. Avantajele acestor dou abordri: metodele anatomice msoar direct unele aspecte ale procesului de real bolii aterosclerotice n sine, prin

urmare, ofer un potenial pentru detectarea anterioare, inclusiv simptome nainte de a ncepe, a bolilor de ateptare i de urmrire de progresie a bolii. Metodele fiziologice sunt adesea mai puin costisitoare i mai sigure i de a le modifica pentru o mai bun pot incetini progresia bolii, n unele cazuri cu o ameliorare marcate. Dezavantaje dintre aceste dou abordri: Metodele anatomice sunt n general mai scumpe si mai multe sunt invazive, cum ar fi IVUS. Metodele fiziologice nu cuantifica starea actual a bolii sau direct de progresie a urmri. Pentru ambele, clinicieni i contribuabilii pri tere au fost lent de a accepta utilitatea acestor abordri mai noi Factori fizologici care cresc riscul Diverse anatomice, fiziologice si factori de risc comportamental pentru ateroscleroza sunt cunoscute. Acestea pot fi mprite n diferite categorii: Vs congenitale dobndite, putnd fi modificat sau nu, clasice sau non-clasice. Punctele etichetate ca "+", sub forma urmtoarea list componentele de baz de "sindrom metabolic". Factorii aduga pentru fiecare alte multiplicatively, cu doi factori de cretere a riscului de ateroscleroza patru ori. Hiperlipidemia, hipertensiune arterial i fumatul, mpreun crete riscul de apte ori mai. Cu toate acestea, infarctele multe implic doar cantiti foarte mici de esut i sunt numite clinic tcut, deoarece persoana care are un infarct nu observai problema, nu caut ajutor medical sau atunci cnd o fac, medicii nu recunosc ceea ce sa ntmplat. Modificabile Avnd n diabet zaharat sau de toleran Alterarea glucoz (IGT) + Dislipoproteinemia (modele vatamati de proteine serice care transport grsimi & colesterolului): + Concentraia seric mare de lipoproteine cu densitate redus (LDL, "ru n cazul n concentraii crescute i mici"), i / sau foarte lipoproteinelor de joas densitate (VLDL) particule, de exemplu, "analiza lipoproteinelor subclas" Concentraia seric sczuta funcionrii lipoproteine de nalt densitate (HDL "de protecie n cazul n care mare i destul de mare" particule), adic, "analiza lipoproteinelor subclas" O LDL: HDL raportul mai mare de 3:1 Tutun pentru fumat, riscul crete cu 200%, dup mai muli ani Avnd n tensiune arterial ridicat +, pe propriul su risc n cretere cu 60% Serice crescute ale concentraiilor proteinei C-reactive Nonmodifiable De vrst avansat De sex masculin

Avnd rude apropiate care au avut unele complicaie a aterosclerozei (de exemplu, boal coronarian sau accident vascular cerebral) Anomalii genetice, de exemplu, hipercolesterolemie familial Mai mic sau nesigur Urmtorii factori sunt de o importan relativ mai mic, sunt incerte sau nonquantitated: Fiind obezi (obezitate, n special centrale, de asemenea, menionate n continuare abdominale sau de sex masculinobezitate de tip) + Un stil de via sedentar n post-menopauz deficit de estrogeni High ingestiei de carbohidrai Aportului de grsimi trans Niveluri serice crescute ale trigliceridelor + Niveluri serice crescute de homocisteina Niveluri serice crescute de acid uric (de asemenea, responsabil pentru gut) Concentraiilor serice de fibrinogenul Lipoproteine serice (a) concentraiile Inflamatia cronica sistemic aa cum sunt reflectate de ctre superioar concentraii normale WBC, HS-CRP crescute i multe alte markeri de snge chimie, cea mai mare nivel de numai de cercetare, n prezent, nu a fcut punct de vedere clinic. Stresul sau simptome de depresie clinic Hipertiroidie (o supra-tiroidian activ) Niveluri serice crescute de insulin + Durata scurta de somn Infeciei cu pneumonie Chlamydia Factori de risc dietetice Relaia dintre alimentare de grsimi i ateroscleroza este un domeniu contencioase. USDA, n piramida alimentar sale, promoveaz o dieta saraca in grasimi, bazat n mare msur pe punctul su de vedere c, de grsime n dieta este atherogenic. The American Heart Association, American Diabetes Association i National Cholesterol Education Program face recomandri similare. n contrast, Prof Walter Willett (Harvard coala de Sntate Public, PI Sntii Asistentelor dou "Study) recomand niveluri mult mai ridicate, n special de grsimi mononesaturate i polinesaturate. Scrierea n tiin, Gary Taubes detaliate c consideraii politice a jucat n recomandrile de organisme guvernamentale. Aceste puncte de vedere diferite ajunge la un consens, dei, fa de consumul de grsimi trans. Rolul dietetice grsimilor oxidat / peroxidare lipidelor (grsimi rnced) la om nu este clar. Animalele de laborator hrnite grsimi rnced dezvolta ateroscleroza. Soarecilor hraniti cu DHA-care conin uleiuri experien ntreruperi marcat pentru sistemele lor antioxidante, precum i a acumulat un volum semnificativ de peroxid n snge, ficat i rinichi.

ntr-un alt studiu, iepuri hrnite diete atherogenic care conin uleiuri diferite s-au gsit s se supun mai mare cantitate de sensibilitate oxidativ de LDL, prin intermediul uleiuri polinesaturate. ntr-un studiu care a implicat iepuri hrnii nclzit ulei de soia, "extrem de indus de ateroscleroz i daunele au fost marcate hepatice histologic i clinic a demonstrat". Rancid grsimi i uleiuri gust foarte ru, chiar i n cantiti mici; oamenii mananca evita-le. Este foarte dificil s se msoare sau estima consumul real uman ale acestor substane. In plus, majoritatea de uleiuri consumate n Unite Statele sunt rafinate, albit, deodorizat i degummed de ctre productori. Uleiurile rezultant sunt incolor, inodor, insipid i s aib o via mai lung de depozitare dect omologii lor nerafinat. Aceasta extinse de prelucrare servete pentru a face peroxidated, uleiuri rnced mult mai evaziv la detectarea, prin intermediul diferitelor simuri umane dect alternativele neprelucrate. Paradoxul francez este observaia c, n ciuda care au o dieta similare cu cele Statele Unite, n ceea ce privete consumul de grsimi, ratele de boal de inim sunt mai reduse n Frana. Exist dovezi care s sugereze paradoxul francez se datoreaz subestimarea a ratelor de o boal de inim, n Frana. Prognoze Dezechilibrelor lipoprotein, superioar normal i, n special crescute de zahr din snge, de exemplu, diabetul i hipertensiunea arterial sunt factorii de risc pentru ateroscleroz; homocisteinei, oprirea fumatului, care iau anticoagulante (anti-ageni de coagulare), care vizeaz factori de coagulare, lund n omega-3 uleiuri de la gras pete sau de uleiuri vegetale, cum ar fi uleiurile de in sau rapita, exercitndu-i pierde greutate sunt concentra obinuite de tratamente care s-au dovedit a fi de ajutor n studiile clinice. int colesterolului seric este n mod ideal, egal sau mai mic de 4 mmol / l (160 mg / dl), i trigliceridelor egal sau mai mic de 2 mmol / l (180 mg / dl). Dovada a crescut faptul c persoanele cu diabet zaharat, n ciuda lor nu au punct de vedere clinic boala detectabil atherosclotic, au debilitate mai grave, de la evenimente aterosclerotice n timp, dect chiar i nondiabetici care au suferit deja evenimente aterosclerotice. Astfel, diabet zaharat a fost actualizat pentru a fi privit ca un echivalent avansat a bolii aterosclerotice. Tratament n cazul n care aterosclerozei duce la simptome, unele simptome cum ar fi angina pectoral pot fi tratate. Non-preparate farmaceutice sunt, de obicei prima metod de tratament, cum ar fi renunarea la fumat i de a practica exercitii regulate. Dac aceste metode nu funcioneaz, medicamente sunt, de obicei urmtorul pas n tratarea bolilor cardiovasculare, i, cu mbuntiri, au devenit din ce n ce mai

metod eficient pe termen lung. Cu toate acestea, medicamentele sunt criticate pentru cheltuiala lor, patentat de control i, ocazional, efecte nedorite. Statinele n general, un grup de medicamente denumite statine a fost cea mai popular i sunt larg prescrise pentru tratarea aterosclerozei. Ele au un numr relativ mic pe termen scurt sau pe termen mai lung efecte secundare nedorite, i tratament multiple comparative / studii clinice sa administrat placebo au destul de constant evideniat efecte puternice n reducerea bolii aterosclerotice "evenimente" i, n general, ~ 25% reducere comparativ a mortalitii n studiile clinice, cu toate c un studiu de design, ALLHAT, a fost mai puin puternic favorabil. Cel mai nou statin, rosuvastatin, a fost primul care a demonstra de regresie a plci aterosclerotice n arterele coronare de IVUS (evaluare intravasculara ecografie). Studiul a fost nfiinat pentru a demonstra efectul principal asupra volumului ateroscleroza ntr-un timp 2 ani-cadru la persoanele cu activ / boal simptomatic (frecven angin pectoral, de asemenea, a sczut semnificativ), dar nu globale rezultate clinice, care era de ateptat s se impun perioade de studiu mai mare de timp; acestor studii, mai rmn n curs de desfurare. Cu toate acestea, pentru majoritatea oamenilor, schimbarea comportamentelor lor fiziologice, de la riscul de obicei ridicat de risc reduse n mare msur, necesit o combinaie de mai multe componente, luate pe o baz de zi cu zi i de la nesfrit. Mai mult i mai multe studii clinice umane de tratament s-au fcut i sunt n curs de desfurare care demonstreaz rezultatele cele mai bune pentru persoanele care folosesc mai multe scheme de complexe i eficace de tratament care fiziologic modificare a modelelor de comportament pentru a mai apropiate de cele om care prezint n copilrie la un moment dat nainte de a ncepe dungile grai care fac . Statine, i cteva alte medicamente, s-au dovedit a avea efecte antioxidante, eventual, o parte din baza lor pentru o parte din succesul lor terapeutice n reducerea cardiace "evenimente". Succesul de droguri statin n studiile clinice se bazeaz pe anumite reduceri a ratei mortalitii, cu toate acestea prin designul proces prtinitoare fa de brbai i de mijloc de vrst, de date este ca, nc, mai puin puternic clare pentru femei i persoane cu vrsta de peste 70. De exemplu, n scandinave Simvastatin Survival Study (4S), primul mare cu placebo controlat, randomizat, studiu clinic al unui statin la persoanele cu boal avansat care au suferit deja un atac de cord, de reducere a ratei mortalitii generale pentru cei care au luat statin, vs . placebo, a fost de 30%. Pentru subgrupul de oameni n procesul care a avut diabet zaharat, reducerea ratei mortalitii ntre statin i placebo a fost de 54%. 4S a fost un proces-5.4 ani, care a

nceput n 1989 i a fost publicat n 1995, dup finalizarea. Au fost 3 mai multe femei moarte, la sfritul proces pe statin dect n grupul placebo, privind consumul de droguri, dac ans sau unele legtur cu statin rmne neclar. Proces asteroid a fost primul care a arta de regresie a bolii volumului actual (a se vedea pagina 8 din hrtie, care arata zonele n seciune transversal a peretelui arterial total de inima, la nceputul i 2 ani de rosuvastatin 40 mg / zi de tratament); cu toate acestea, sa design-ul nu a fost capabil de a "dovedi" problema de reducere a mortalitii n msura n care nu au inclus un grup placebo, persoane fizice oferit de tratament n cadrul studiului au avut boal avansat i de promovare a unui bra comparaie cu placebo a fost considerate a fi lipsite de etic. Prevenirea primar i secundar Combinaii de statine, niacina, absorbia intestinal a colesterolului-suplimente inhibarea (ezetimibe i alii, i ntr-o msur mult mai mic fibrai) au fost cele mai de succes din schimbarea comune, dar sub-modele optime de lipoproteine i rezultatele grupului. n multe prevenirea secundar i de mai multe studii primare de prevenire, mai multe clase de exprimare lipoproteine (mai puin n mod corect a numit "reducerea nivelului de colesterol") modificarea agenii i-au redus n mod constant, nu doar atac de cord, accident vascular cerebral i de spitalizare, dar, de asemenea, toate-determina ratele de mortalitate. Primul dintre statin mari de prevenire secundar comparative / studiile placebo, tratament a fost scandinave Simvastatin Studiul de supravieuire. (4S), cu peste 15 mai mult de extindere, prin intermediul mai recent asteroid studiu publicat n 2006. Prima de prevenire primar studiu comparativ de tratament a fost AFCAPS / TexCAPS cu mai multe statine mai trziu comparative / studiile placebo, tratament, inclusiv EXCEL., ASCOT i SPARCL.While studiile statin toate au fost n mod clar favorabil pentru mbuntirea rezultatelor umane, numai asteroid a artat semne de regresie aterosclerotice ( uoar). Pentru ambele studii umane i animale, cele care au prezentat semne de boal de regresie au folosit toate mai agresive combinaie de strategii agent de tratament, aproape ntotdeauna, inclusiv niacin. Dieta si suplimente alimentare Vitamina B3, niacina AKA, in doze farmacologice, (n general, 1000 la 3000 mg / zi), vndute n OTC multe i formulri baz de prescripie medical, tinde s mbunteasc (a) nivelurile HDL, mrimea i funcia, (b) trecerea de distribuie a particulelor LDL mai mare mrimea particulelor i (c) lipoproteine mai mic (a), o ateroscleroza promovarea varianta genetic de LDL. n plus, rspunsurile individuale la niacina de zi cu zi, n timp ce cea mai mare parte evident dup o lun la doze eficace, tinde s-i continue pentru a mbunti n continuare lent n

timp. (Cu toate acestea, nelegerea atent a pacientului modul de a realiza acest lucru, fr simptome tulburarea ordinii este necesar, chiar dac de multe ori nu atins.) Activitatea de cercetare privind creterea HDL-concentrarea de particule i funcia, dincolo de efectul niacina de obicei / rspuns, chiar mai important, avanseaz lent. Schimbarile de dieta pentru a obine beneficii au fost mai controversat, n general, mult mai puin eficiente i mai puin pe scar larg pentru a aderat cu succes. Unul dintre motivele-cheie pentru acest lucru este c cea mai mare de colesterol, de obicei 80-90%, in interiorul corpului este creat si controlat de producia intern de ctre toate celulele din organism (valabil pentru toate animalele), de obicei, cu puin mai mare fa de producia de celule hepatice hepatic / . (Structura celulei se bazeaz pe membrane de grsime s se separe i organiza intracelular de ap, proteine i acizi nucleici i a colesterolului este una din componentele tuturor membranelor celulare de origine animal.) Caldwell B Esselstyn Jr. MD a avut un articol publicat n Preventiv Cardiologie 2001; 4: 171-177, n care el a publicat angiograms care arat regresia aterosclerozei cauzat de o dieta vegetariana foarte sczut de grsime, n unele cazuri, cu medicamente de scdere a colesterolului. n timp ce cantiti absolute de producie varia n funcie de individ, mediile de grup pentru coninutul total de organismul uman de colesterol n rndul populaiei SUA frecvent despre a alerga ~ 35,000 mg (presupunnd c macr construi; variaz n funcie de greutatea corporal i de a construi), precum i ~ 1000 mg / zi de producie n curs de desfurare. Aportul alimentar joac un rol mai mic, 200-300 mg pe zi, fiind valori comune; pentru vegetarieni pur, n esen, 0 mg / zi, dar acest lucru de obicei nu se schimb situaia foarte mult deoarece creterile de producie intern pentru a compensa n mare parte pentru consumul redus. Pentru muli, n special cele cu mai mare de mas corporal optim i creterea glicemiei, reducerea glucidelor (n special formele simple) de admisie, nu, grsimi sau colesterol, este de multe ori mai eficace pentru mbuntirea modelelor de exprimare lipoproteine, de greutate i valorile de glucoz din snge. Din acest motiv, autoritile medicale mult mai puin frecvent promova conceptele dietetice sczut de grsime dect a fost de obicei n cazul anterior cu privire la anul 2005. Cu toate acestea, dovezi c a crescut prelucrate, n special nonindustriale hidrogenare enzimatice produse de grsimi trans, spre deosebire de cis-grsimi naturale configurat, care celulele vii produc n primul rnd, este un risc semnificativ pentru sntate. Suplimente nutritive de Omega-3 uleiuri, n special cele din muchi de nite ap, sare adncime de via specii de pete, de asemenea, au semne clinice de efecte semnificative de protecie astfel cum a confirmat de 6 dublu-orb, controlate placebo, studiile clinice umane. Exist, de asemenea, o varietate de elemente de prob, dei mai puin robuste, c homocisteinei i nivelurile de acid uric, inclusiv n

intervalul valorilor normale a promova ateroscleroza si, c reducerea aceste niveluri este util, pn la un punct. La animale deficit de vitamina C a fost confirmat ca un rol important n dezvoltarea de hipercolesterolemie i ateroscleroza, dar, datorit placebo, din motive etice studii controlate umane sunt imposibil de a face. Vitamina C actioneaza ca un antioxidant n vase i inhib proces inflamator. Aceasta are proprieti terapeutice pe tensiune arterial crescut i de fluctuaie sale, i rigiditate arterial n diabetul zaharat. Vitamina C este, de asemenea, un regulator natural de colesterol i doze mai mari (peste 150 mg / kg pe zi) poate conferi o important protecie mpotriva aterosclerozei, chiar i n situaia de Valori crescute ale colesterolului. Scar de vitamina C pe beneficiile sistemului cardiovascular a condus mai muli autori la teoria, c deficit de vitamin C este cauza principal a bolilor cardiovasculare. Teorie a fost unificat de dou ori ctigtor al Premiului Nobel Linus Pauling i Matthias Rath. Ei sugereaz, c manifestrile clinice ale bolilor cardiovasculare sunt depire doar mecanismele de aparare ale organismului, care sunt implicai n stabilizare a peretelui vascular, dup ce este slbit de deficit de vitamina C , precum i degradarea ulterioar colagen. Ei discuta predispoziiile genetice metabolice i de mai multe i de pathomechanism lor. Procesele de la Vitamina E s-au facut, dar ei nu au reuit s gseasc un efect benefic, din diverse motive, dar, pentru unele pacienii cu risc crescut de ateroscleroza pot exista anumite avantaje. Menokina (vitamina K2), dar nu filochinon (vitamina K1), consumul este asociat cu un risc redus de CHD mortalitate, mortalitatea de toate cauzele i sever calcifiere aortica. S-a sugerat faptul c excesul de fier pot fi implicate n dezvoltarea de ateroscleroz, dar un studiu a constatat reducerea de magazine de fier din organism la pacienii cu boal simptomatic arterelor periferice prin flebotomie nu reduce semnificativ toate mortalitii generale sau de deces, plus nonfatal infarct miocardic i stroke.Further studii pot fi justificat. Interventia chirurgicala Alte tratamente fizice, de ajutor pe termen scurt, s includ proceduri de angioplastie minim invazive, care pot include Stenturi s extind fizic arterelor redus i intervenii chirurgicale majore invazive, cum ar fi operatie bypass, pentru a crea conexiuni de snge suplimentare de alimentare cu care s mearg n jurul zonelor mai sever redus. Profilaxie Pacienii cu risc de ateroscleroz legate de bolile sunt din ce n ce n tratament profilactic cu aspirina doze sczute i o statin. Inciden

ridicat a bolilor cardiovasculare Wald a condus i a Legii s propun un Polypill, o dat pe zi, pilula care conin aceste dou tipuri de droguri n plus fa de un inhibitor ECA, diuretice, beta-blocant, i a acidului folic. Ei susin c absorbia ridicat de ctre populaie, n general de o astfel de Polypill ar reduce mortalitatea cardiovasculare cu 80%. Acesta trebuie s fie subliniat, totui, c acest lucru este pur teoretic, dup cum Polypill nu a fost testat ntr-un studiu clinic. Tratamente medicale de multe ori se concentreze n principal asupra simptomelor. Cu toate acestea, n timp, tratamente care se concentreaz pe reducerea stau la baza proceselor de ateroscleroza, spre deosebire de pur i simplu tratarea simptomelor care rezult din aterosclerozei, s-au dovedit prin studii clinice pentru a fi mai eficiente. Pe scurt, cheia de la abordri mai eficiente a fost mai bun nelegere a naturii rspndit i insidioas a bolii i de a combina diverse strategii multiple de tratament, nu se bazeaz doar pe unul sau mai puine abordri. n plus, pentru aceste abordri, cum ar fi comportamente de transport lipoproteine, care s-au dovedit a produce cel mai mare succes, adoptarea de strategii agresive, mai multe combinaii de tratament a produs, n general, rezultate mai bune, att nainte ct i mai ales dup ce oamenii sunt simptomatice. Deoarece subiaz sngele muli, n special salicilai, cum ar fi warfarina i aspirina subire de snge prin interferarea cu Vitamina K, exist dovezi recente care subiaz sngele care locul de munc prin acest mecanism, de fapt, se poate agrava calcifiere arterial pe termen lung, chiar dac acestea subire de snge pe termen scurt. Cercetri recente O indicaie a rolului HDL pe aterosclerozei, a fost cu Apo rare-A1 Milano varianta uman genetic al acestei proteine HDL. Un mic studiu pe termen scurt, folosind Apo sintetizat bacteriene uman-A1 Milano HDL la persoanele cu angin instabil a produs o scdere destul de dramatic a volumului msurat placa coronarian, n doar 6 sptmni fa de creterea volumului de obicei n plci n aceste randomizai la placebo. Studiu a fost publicat n JAMA la nceputul anului 2006. Lucrri n curs de plecare n anii 1990, ar putea duce la studiile clinice la om-, probabil, cu aproximativ 2008. Apo Acestea pot utiliza sintetizat-A1 Milano HDL direct. Sau, ele pot folosi metode de transfer a genelor pentru a trece capacitatea de a sintetiza Apo-A1 Milano HDLipoprotein. Metode de a crete lipoproteine cu densitate nalt (HDL) concentraiilor de particule, care, n unele studii la animale, n mare msur, inverseaz i s nlture atheromas, sunt dezvoltate i cercetate. Niacina are efecte creterea HDL (cu 10 - 30%) i a demonstrat un beneficiu clinic n proces de droguri coronarian de proiect i este frecvent utilizat n asociere cu ali ageni de lipoproteine pentru a mbunti eficacitatea lipoproteine de schimbare n bine. Cu toate

acestea cele mai multe persoane au simptome tulburarea ordinii pe termen scurt, cu nroirea feei reacii, mai ales iniial, i astfel de lucru cu un medic cu o istorie de experien de succes cu punerea n aplicare niacina, o selecie atent a de brand, strategie de dozare, etc sunt, de obicei critice pentru succes. Cu toate acestea, creterea HDL prin orice mijloace care nu este neaprat de ajutor. De exemplu, torcetrapib de droguri este agentul cel mai eficient n prezent, cunoscut pentru creterea HDL (cu pn la 60%). Cu toate acestea, n studiile clinice, de asemenea, ridicate Decese cu 60%. Toate studiile cu privire la acest medicament au fost suspendate n decembrie 2006. Procesul asteroid a folosit o mare doz de rosuvastatin-statin de obicei cu doza cea mai puternic / rspuns de coresponden track record (att pentru LDLipoproteins i HDLipoproteins.) Aceasta a constatat plci de reducere (intima + mass-media de volum). Tratament suplimentar mai multe rosuvastatin / placebo, studiile pentru evaluarea rezultatelor clinice, altele sunt n curs de desfurare. Aciunile de macrofagelor conduce progresie plci aterosclerotice. Imunomodulare al aterosclerozei este termenul pentru tehnicile care modula funcia sistemului imunitar, n scopul de a suprima aceast aciune macrofage. Imunomodulare a fost urmrit cu succes considerabil n ambele oareci i iepuri din moment ce aproximativ 2002. Planuri pentru studii clinice umane, pentru a sperat cu circa 2008, sunt n curs de desfurare. Cercetrile privind expresie genetic i a mecanismelor de control progreseaz. Subiectele includ PPAR, cunoscute ca fiind importante de zahr n snge i variantele de producie lipoproteine i funcia; Variante multiple de proteine care formeaz particule de lipoproteine de transport. Unele cercetare controversate a sugerat o legtur ntre ateroscleroza, precum i prezena mai multor nanobacteria diferite n artere, de exemplu, Chlamydophila pneumoniae, dei studiile de curent tratamentul cu antibiotice cunoscute a fi, de obicei eficient n cretere suprimarea sau uciderea aceste bacterii nu au fost ncununate de succes n mbuntirea rezultatelor . Aabordri menionate mai sus, pentru c ei se confrunt cu raspunsuri nnscut de gazd de a promova ateroscleroz, au perspective mult mai mare pentru a avea succes. National Heart, Lung, and Blood Institute (NHLBI) si Centrul National pentru complementare si alternative de Medicina (NCCAM) sponsorizat Proces pentru a evalua chelatizare Therapy (tact). Scopul acestui studiu este de a determina sigurana i eficacitatea tetra etilen diamin-acetic (EDTA) chelatizare tratamentului la persoanele cu boala coronariana. EDTA terapia chelatizare implic administraiile repetat a unui acid amino-sintetic pentru a reduce plci aterosclerotice i depozite minerale, altele n ntreaga sistemul cardiovascular. Rezultatele tact va

oferi fie un rezultat pozitiv semnificativ sau de un rezultat nul informativ, pe care decizie raional clinice i de procesul de luare a politicii n domeniul sntii se poate baza. Teoria Hemorheologic-hemodinamice Teoria atherogenesis descris mai sus este prezentat n mare msur, ca fapt., Reprezentnd totodat opinia majoritii, aceasta teorie are cteva puncte slabe. Agresive de reducere de ser de LDLcolesterol utiliznd terapia doze mari de statine las nc risc semnificativ de negative evenimente cardiovasculare la pacienii cu risc ridicat. n ciuda scdere ser LDL-colesterol la mai puin de 100 mg / dl, riscul estimat de evenimente adverse la pacienii cu boal coronarian stabilit este estimat la 9% pe an. Acest lucru, coroborat cu eecul torcetrapib n studiile clinice, ar trebui s reexaminare prompt a teoriei atherogenesis mainstream. Mai mult, LDL oxidat este distribuit larg n ambele arterele i venele, aceasta din urm de care nu se dezvolta ateroscleroza. De distribuie a leziunilor precursoare presupuse, cu baleiaj gras, slab coreleaz cu distribuia de placi fibroase. Teoria curentul principal al atherogenesis nu explic localizarea plci fibroase la apropierea de schimbare a geometriei arteriale, cum ar fi ramuri, curbe, i dilatations. Teoria Mainstream ofer nici o explicaie pentru ateroscleroza accelerat asociat cu hipertensiune arterial. n cele din urm, teoria mainstream nu poate explica prezena plcilor fibroase n sintetic grefe arterio-venoase. Hemorheologic-hemodinamice teorie susine c ateroscleroza este o boal a staz de snge, care promoveaz organizarea unui trombilor ntr-o plci aterosclerotice. [60] staz de snge predispune la tromboz, cum este descris n triada Virchow lui. Factorii de risc pentru ateroscleroz a crea zone mai mari de a sczut de forfecare (debit), prin creterea vscozitate de snge, rigiditate arterial, sau ambele. Ambele dintre aceste anomalii sunt vzute n asociere cu inaintarea in varsta, hipertensiune arterial, diabet zaharat, fumatul, i obezitii. [60] [63] hemorheologic-postuleaz hemodinamice teoria c acelai proces patologic, tromboz, conduce la ambele plci de dezvoltare i de complicaie sale , tromboz suprapus i infarct. Numele reflect faptul c interaciunea dintre hemorheologic, adic, fluxul de snge, precum i hemodinamice, de exemplu, viteza de snge, pulsatility, si geometrie arterial, factori duce la ateroscleroza. Staz Viscozitate i localizate n artere n timpul systole, exist un gradient de vitez de snge, cu cea mai mare viteza in centrul navei i cel mai sczut fa de peretele arterial. n zonele de vasculare ramificat, curbare i dilatarea, snge focal punerea n comun a se produce n mediul de sczute forfecare mpotriva peretele arterial n cazul n care viteza de snge depete o valoare critic de numrul Reynolds (a se vedea mai jos). Acest fenomen este observat n natur de apa care curge rapid atunci

cnd ntlnete un obstacol, formnd Eddies i piscine. Sngele este un non-Fluide newtoniene, i viscozitii sale crete progresiv cu scderea de forfecare. n zonele de punerea n comun, un cerc vicios se poate dezvolta, n care a crescut vscozitatea duce la fluxul de sczut, ca urmare a creterii vscozitii i scderea debitului, ceea ce duce n cele din urm la staz i tromboza, n lipsa de activitate fibrinolitic adecvate. Scderea fluxul de snge promoveaz tromboza prin scderea aflux de molecule fibrinolitic i scderea eflux a activat factori de coagulare. Trombocite activat de forfecare mari n coloana central de snge pot fi direcionate spre imediata apropiere a peretelui arterial de curenii de Eddy. n aceste zone, scderea fluxului sanguin scade producia endoteliale din molecule cu activitate antitrombotice, cum ar fi de oxid nitric i de prostaciclin, promovarea n continuare a tromboz. Acest lucru este nrudit cu disfuncii endoteliale, care, n mainstream teoria atherogensis este considerat a fi cauzate de efectele presupuse cytopathic de joasa oxidat - lipoproteine cu densitate. Rigidizarea arterial Creterea rigiditate arterial accelereaz ateroscleroza, prin creterea vitezei de arterial de vrf de snge, crescnd astfel numrul de Reynold, care indic tendina de un lichid care curge de a dezvolta piscine i a curenilor Eddy n asociere cu schimbarea geometrie arterial. n mod normal, aorta conforme, o parte a fiecrui volum accident vascular cerebral este stocat n systole si propulsat cu viteza mai mic n diastol, crearea de fluxul de snge n cea mai mare a ciclului cardiac. O zon de punerea n comun a creat de viteza mare ar disprea n timpul fluxului de lent diastolice, precum i orice microthrombus acumulate ar fi dispersate. ntr-o aorta perfect rigid, ntregul volum accident vascular cerebral ar fi expulzat n systole. Avnd n vedere volum constant accident vascular cerebral, de conservare a masei impune creterea vitezei de arterial de vrf de snge cu creterea rigiditatea arterial. [63] n plus, nici o vitez redus debit diastolice se va produce, astfel nct un bazin formate n timpul fluxului de viteza mare a tensiunii arteriale sistolice va persista pe tot parcursul ciclului cardiac. Acest lucru va permite timpul necesar pentru creterea economic trombilor i organizarea ulterioar (a se vedea mai jos). n plus, a crescut viteza de vrf arterial va mri Shear-activiation mediate de trombocite. Organizarea de trombilor murale JB Duguid promovat ideea c plcilor aterosclerotice dezvolta de la organizarea de trombilor murale n anii 1940 i 50's. Trombilor arteriale au tendina de a rmne localizat la mediul sczut forfecare a peretelui arterial, din cauza vitezei mari de snge, n partea central a arterei. Aceste trombilor sunt stiu ca "murale" sau "parietale." n vene, gradientul de viteza ntre centrul navei i peretele vasului este mic.

Astfel, trombilor n vene au mai multe anse de a deveni ocluzive, la fel ca n tromboz venoas profund. Acesta este motivul pentru ateroscleroza este limitat la artere. n cazul n care trombilor persist, fie n artere sau vene, ei sufer de organizare, n care circul fibrocytes colonizeze trombilor i diferenierea n celule capabile s produc colagen i a markerilor de difereniere musculaturii netede, cum ar fi Actin musculare netede. Rolul lipoproteinelor n aterogenez Teoria Hemorheologic- hemodinamice prezice c lipoproteine cu densitate joas (LDL) ar trebui s creasc vscozitate de snge iliporotein de nalt densitate (HDL) ar trebui s scad vscozitate de snge, care a fost demonstrat experimental. Eritrocitele sunt separate de o distan minim intercelular de aproximativ 15 nanometri cauzate de repulsie electrostatice, datorit acidului sialic de pe suprafaa membranei celulare. LDL are un diametru de particule de 18 - 40 nanometri, suficient de mare pentru a lega simultan la dou eritrocite i formularul de agregate de eritrocite. Erythrocyte agregate cretere viscozitate de snge la forfecare mici, prin creterea ineria de particule n suspensie. HDL, cu un diametru de particule de 8 - 12 nanometri, este prea mic pentru a promova agregare eritrocite. n schimb, n competiie cu LDL de bandaj de eritrocite, acesta antagonizeaz agregare a hematiilor i scade viscozitate de snge. Agregate de eritrocite sunt slabe, i progresiv distrupted cu forfecare n cretere. Avnd n vedere relaia de LDL la viscozitate de snge, nu este surprinztor faptul c hipercolesterolemie este un factor de risc pentru ambele ateroscleroza i tromboz venoas profund. Teoria Hemorheologic- hemodinamice explic risc semnificativ rmase din adverse evenimente cardiovasculare la pacienii cu boal coronarian stabilite, n ciuda agresiv de scdere a colesterolului LDLutiliznd terapia doze mari de statin. n ciuda scdere ser LDLcolesterol la mai puin de 100 mg / dl, riscul de evenimente cardiovasculare majore la aceti pacieni este estimat a fi de 9% pe an. O astfel de terapie nu abordeaz consecinele negative de viscozitate de snge arterial rigidizare, sau a crescut cauzate de ali factori. Teoria Hemorheologic- hemodinamice explic existena unor plci aterosclerotice n sintetic grefe arterio-venoase. Acestea ofer un mediu extrem de hemodinamice, n cazul n care extrem de mare vitez de snge curge printr-un vas curbat. Aceste nave sunt predispuse la tromboz i de dezvoltare a plcilor aterosclerotice, n ciuda anticoagulant. Aceste nave nu dispun de un Tunica mass-media, care a primit nelepciunea susine este originea celulelor musculare netede n plci aterosclerotice, prin intermediul migraiei. De identificare a fibrocyte ofer o explicaie alternativ pentru originea celulelor musculare netede n plci aterosclerotice. Fiind n mare msur nensufleite, capacitatea acestor nave pentru a rspunde la un accident

cu un rspuns inflamator, cauza care incit de ateroscleroz conform teoriei integra atherogenesis, ar fi foarte limitate. Mai mult, aceasta teorie explic beneficia de donare de snge i de but cantiti mari de ap. Ambele al acestor intervenii risc foarte sczut a reduce viscozitate de snge. Hemorheologic-hemodinamice elimina dependena de baleiaj grase n atherogenesis. Grai dungile n mod obinuit se rezolv fr sechele. Acest lucru este recunoscut de ctre teoria atherogenesis mainstream, care se afl n imposibilitatea de a prezice de ce o dung special grai avanseaz ntr-un plci aterosclerotice n timp ce majoritatea regres. De cretere a mrimii particulelor i a crescut de HDL-low-viscozitate de forfecare de snge cauzate de terapie torcetrapib ar putea considerare pentru creterea mortalitii cardiovasculare observate n studiile clinice. Creterea vitezei de arterial de vrf de snge i rigidizarea arterial poate juca, de asemenea, un rol n moartea subit de cauz cardiac asociat cu efort fizic. Rezultatele eforturilor fizice n creterea produciei cardiace i creterea tensiunii arteriale, ambele care ar putea mri viteza de vrf arterial, dei efectul a produciei cardiac crescut la viteza de vrf de snge arterial, n aceast situaie nu a fost studiat. Creterea numrului Reynolds ar putea duce la tromboza coronarian acut aa cum este descris mai sus. Viitorul Validarea hemorheologic-teoria hemodinamice va necesita un studiu prospectiv pentru a determina dac msurarea vscozitii sngelui i viteza de vrf arterial de snge identific subiectele risc crescut de ateroscleroz simptomatic mai bine dect markeri de rutin, cum ar fi analiza lipidelor.