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Objective: The aim of the study was to know the pattern of presentation of Coronary Artery Disease in patients admitted to Algamhouria modern general hospital. Background: Coronary artery disease (CAD) is a major public health problem worldwide, We therefore tried to evaluate the different manifestation of patients with ACS in our patients . Methods: This prospective study which was done in algamhouria modern general hospital in Aden enrolled 124 patients with ACS in the period between 1st July 2008_31st December 2008.ACS definition included ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina (UA). Results: Out of 124 patients enrolled in this study,(78.2% )were male and( 21.8%) were female. Our patients had mean ages of 56.17±11.9 years, female mean age 57.26±9.863 and male mean age 55.87±12.534. ST segment elevation myocardial infarction (STEMI)represents (37.9%), non-ST segment elevation myocardial infarction(NSTEMI)occurs in (33.1%),and unstable angina (UA)was seen in(29%)of patients. 43.5% of those admitted with ACS were >=60years old, The young patients were more likely to develop an STEMI than their elder groups (14.5%vs12.1%;p value=0.008), and NSTEMI was found more common in older group (21%). Women had presented more likely to present with unstable angina 44.44%and more often had atypical presentations14.5% (p=0.000).Risk factors such as cigarettes smoking, khat chewing, hypercholesterolemia ,obesity and a family history were more frequent in the young patients, whereas diabetes, overweight and hypertension were less frequent.VI THE CLINICAL PRESENTATION OF ACUTE CORONARY SYNDROME- ALGAMHORIA HOSPITAL -ADEN Patients with STEMI were more often cigarette smokers, khat chewing, +ve family history(p=0.019), but less often with a history of diabetes, hypertension. Younger patients more often had typical presentations, Younger patients had a lower in-hospital mortality rate, lower incidence of heart failure and other complications than older patients. women not only ranked higher Acute Coronary Events but also had increased in-hospital mortality 60% than 40% in men. myocardial infarction patients were more complicated 48.9% than UA patients13.9% (p=0.000). In-hospital mortality occurred (60%) in ST segment elevation myocardial infarction patients and (20%)in UA and NSTEMI patients .


Conclusions: In this study, we provide a description of ACS patient, which allows the evaluation of the demographic characteristics and in-hospital mortality, The mortality rates in ACS remain high with females and elderly individuals. A national prevention program at community level as well as high risk groups should be implemented sooner to prevent the expected epidemic of CAD.


Introduction

Acute coronary syndrome encompasses a spectrum of coronary artery diseases, including unstable angina, ST-elevation myocardial infarction (STEMI; often referred to as "Q-wave myocardial infarction"), and non-STEMI (NSTEMI; often referred to as "non-Q-wave myocardial infarction"). The term "acute coronary syndrome" is useful because the initial presentation and early management of unstable angina, STEMI, and NSTEMI frequently are similar.(28) In 2005 the total mortality from all CHD in the UK was 101,000.This is one fifth of the total number of deaths from all causes. Death rates are highest in the few hours following a cardiac event. Approximately 40 percent of people will die within 24 hours of an event, often before they reach hospital. A further 10 percent will die within 28 days. STEMI reduces long term survival. A study looking at survival rates in a group of 40-59 year old men found that of those who were alive after 28 days, 76 percent survived to five years and 63 percent survived to10 years. The survival rates for men of a similar age with no evidence of CHD were 97 percent and 93 percent. (29) Even with this aggressive practice pattern, 2% to 8% of patients with acute MI are discharged from emergency departments inappropriately (30). Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the world and acute coronary syndromes (ACS) is the commonest causes of mortality in patients with CAD.(31) In the United States of America (USA), for example, CAD is the leading cause of death in adults, accounting for approximately one-third of all deaths in subjects over the age of 35-years.(32) While age adjusted mortality from CAD is gradually falling in developed countries, it is set to become an epidemic in developing countries, and over the next 20-years will probably become the most important global health problem.(33) According to the World Health Organization, developing countries contributed to 85% of cardiovascular disease (CVD) deaths. (34) CHD is forecast to be the most common cause of death in India by the year 2020(35)


,South Asians on the other hand, have the highest rates of Coronary Artery Disease (CAD) around the globe (36). Coronary heart disease (CHD) is one of the most common causes of morbidity and mortality in different communities (8) CVD made up 16.7 million, or 29.2% of total global deaths in 2003, 80% of which took place in the developing world. If the incidence goes on unchecked CVD will be the leading cause of death in developing world by 2010.(37) Epidemiological aspect:- Acute myocardial infarction (AMI) remains a public health problem of epidemic proportions. Recent data from the American Heart Association (AHA) reveal a prevalence of myocardial infarction (MI) of 1.9 - 5.2%, which varies by age, sex, and ethnicity. (38) In the United States annually, there are 565,000 first-time, and 300,000 recurrent, myocardial infarctions (38) and in 2006, The AHA estimates that 700,000 American will have their first coronary event in 2006, and 500,000 will have a recurrent event.(6) An epidemic of coronary heart disease (CHD) began during the 20th century in most industrialized countries, where CHD is a leading cause of mortality among adults (39). The Joint European Society of Cardiology/American College of Cardiology (ESC/ACC) Committee proposed a new definition of myocardial infarction (MI) based predominantly on the detection of the cardiospecific biomarkers troponin T and troponin I.(40) History of the patient, the ECG and enzymes (markers) help to diagnose the MI. A persistent ST elevation is helpful, but not sensitive enough for diagnosis of acute myocardial infarct in patients with concomitant ST segment elevation. Extended praecordial chest leads only marginally increase the sensitivity of the ECG diagnosis of AMI. (41) In order to reduce the global burden of CAD ,many strategies have been put in place. These strategies have been implemented over a decade ago in countries like the U.S., Sweden and Norway and are only starting to bear fruit now, reflective of the indolent silently progressive nature of CAD. The strategies were also formulated after extensive clinical and epidemiological research. The three target areas for treatment and prevention of CAD are: 1) the identification of persons at risk of developing CVD and predisposing factors. 2) the development and clinical evidence of drugs and other interventional procedures that halt or modulate atherosclerosis. 3) the implementation of clear strategies based on sound clinical evidence at all stages of the disease and clinical manifestation.(42) More recently, the WHO MONICA Study(43) and other surveillance and intervention studies, such as the Lipid Research Clinics in the United States,(44)have modified further the definition of CHD cases. These changes are


usually based on a greater specification to the original WHO definition to allow for application in different settings. Advancing diagnostic technology, therapeutic interventions, and changing disease presentation in recent years forces a reevaluation of case definitions for acute CHD. New biomarkers, cardiac troponins and creatine kinase (CK)-MB mass provide information that is more sensitive and/or specific in detecting even minor myocardial cell damage. (45)New imaging methods, such as MRI and radioisotope imaging, although not widely available today, will add to the diagnostic tools. These developments were recently reviewed in a Joint European Society of Cardiology/American College of Cardiology Workshop on the Redefinition of Myocardial Infarction. (46)That report, published in 2000, provided direction for clinicians faced with changing diagnostic testing and new information. Another recent report extends advice to clinical trials.(47) The incidence of angina, acute myocardial infarction, and sudden death, the major clinical manifestations of CHD assessed epidemiologically, varies according to risk factors, age, gender, and ethnicity at the individual level and among countries, regions, and social strata within countries at the population level, and it has varied markedly over time. Unstable angina, acute myocardial infarction, and acute ischemic episodes result from sudden, life-threatening, impaired blood supply to the myocardium and are usually precipitated by lumen-obstructing thrombi that are superimposed on lipid-rich coronary artery plaques after they rupture . Until recently, the "natural history" of coronary atherosclerosis at these advanced stages of the disease was resistant to therapeutic intervention; it now can be converted to a favorable clinical course modifiable by medical intervention, which is the subject matter of clinical CHD epidemiology and its clinical trials (48) . PATHOPHYSIOLOGY OF ACS:- The spectrum of acute coronary syndrome (ACS) is broad and encompasses myocardial infarction as well as unstable angina. Coronary atherosclerosis is a chronic, slowly progressive disease, and has been shown to begin in its early stages even in the teenage years (49) . While in some patients coronary artery disease (CAD) is not symptomatic until a coronary lesion has progressed to cause a greater than 70% luminal stenosis, many patients present to medical attention with acute myocardial infarction before having been diagnosed with CAD (50) . ACS begins when a disrupted atherosclerotic plaque in a coronary artery stimulates platelet aggregation and thrombus formation. It's the thrombus occluding the vessel that prevents myocardial perfusion. In the past, researchers supposed that the narrowing of the coronary artery in response to


thickening plaque was primarily responsible for the decreased blood flow that leads to ischemia, but more recent data suggest that it's the rupture of an unstable, vulnerable plaque with its associated inflammatory changes—or "most cases of infarction are due to the formation of an occluding thrombus on the surface of the plaque."(51) Myocardial cells require oxygen and adenosine 5[beta]-triphosphate (ATP) to maintain the contractility and electrical stability needed for normal conduction.(52) As myocardial cells are deprived of oxygen and anaerobic metabolism of glycogen takes over, less ATP is produced, leading to failure of the sodium–potassium and calcium pumps and an accumulation of hydrogen ions and lactate, resulting in acidosis. At this point, infarction—cell death—will occur unless interventions are begun that limit or reverse the ischemia and injury. During the ischemic phase, cells exhibit both aerobic and anaerobic metabolism. If myocardial perfusion continues to decrease, aerobic metabolism ceases and eventually anaerobic metabolism will be significantly reduced. This period is known as the injury phase. If perfusion is not restored within about 20 minutes, myocardial necrosis results and the damage is irreversible. (52) Impaired myocardial contractility, the result of scar tissue replacing healthy tissue in the damaged area, decreases cardiac output, limiting perfusion to vital organs and peripheral tissue and ultimately contributing to signs and symptoms of shock.(52) Knowledge concerning the pathophysiology of atherosclerosis has accumulated rapidly. Abnormal lipid metabolism or excessive intake of cholesterol and saturated fats—especially when superimposed on a genetic predisposition—is important in early stages of the atherosclerotic process . The initial step is the "fatty streak," or subendothelial accumulation of lipids and lipid-laden monocytes (macrophages). LDLs are the major atherogenic lipid. HDLs, in contrast, are protective by virtue of their role in reverse cholesterol transport, removing cholesterol from the vascular wall. The pathogenetic role of other lipids, including triglycerides, is less clear. LDLs undergo in situ oxidation, which makes them more difficult to mobilize as well as locally cytotoxic. Macrophages migrate into the subendothelial space and take up lipids, giving them the appearance of "foam" cells. As the plaque progresses, smooth muscle cells also migrate into the lesion. At this stage, the lesion may be hemodynamically insignificant, but endothelial function is abnormal and its ability to limit the entry of lipoproteins into the vessel wall is impaired. If the plaque remains stable, a fibrous cap forms, the lesion becomes calcified, remodeling of the vessel wall occurs, and ultimately the


vessel lumen may become narrowed, although extensive atherosclerosis may be present even before this occurs.(4) A number of microanatomic mechanisms underlie acute coronary thrombosis. According to autopsy studies—clearly biased toward fatal outcomes—a through-and-through rupture of the plaque’s protective fibrous cap most commonly causes lethal coronary thrombosis. (53) Other mechanisms that account for a minority of fatal coronary thromboses include superficial erosion, intraplaque hemorrhage, and the erosion of a calcified nodule (54) Thus, physical disruption of the atherosclerotic plaque accounts for almost all acute coronary thromboses. Disrupted plaques provoke thrombosis in several ways. First, contact with collagen in the plaque’s extracellular matrix can trigger platelet activation. Second ,tissue factor TF produced by macrophages and smooth muscle cells (SMCs) activates the coagulation cascade. (55) The disrupted plaque thereby represents a "solid-state" stimulus to both thrombosis and coagulation; these pathways reinforce each other, as thrombin generation amplifies the activation of platelets and other cells in the lesion. Conversion of fibrinogen to fibrin and release of von Willebrand factor from activated platelets can provide the cross-linking molecular bridges between platelets that yield the dense, 3-dimensional network of platelets entrapped in fibrin characteristic of the "white" arterial thrombus. In addition to the solid state of the disrupted plaque, the "fluid phase" of blood can predispose toward coronary thrombosis. Plasminogen activator inhibitor-1 (PAI-1) extinguishes the body’s natural fibrinolytic mechanism that combats the persistence and accumulation of thrombi by inhibiting urokinase-like and tissue-type plasminogen activators. Circulating levels of PAI-1 increase in diabetes and obesity, and mediators of hypertension such as angiotensin II can augment PAI-1 expression by various cell types.(56) Furthermore, disrupted plaques can elaborate particulate TF, which can heighten the thrombogenicity of blood. (55) These fluid-phase changes led to the concept of the "vulnerable patient," thus augmenting our appreciation of the so-called "vulnerable plaque." (57) In the context of ACS, the distal embolization of TF-rich debris spewing into the bloodstream from the core of the suddenly disrupted plaque may promote distal thrombosis in the microcirculation. (58) We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the


"fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. (59) These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.(59) In contrast to the long-standing knowledge that neurohormonal activation is deleterious in the acute coronary syndromes, the realization that inflammation has a critical role in the pathogenesis of these syndromes has occurred relatively recently. Inflammation contributes on several levels to the rupture of vulnerable atherosclerotic plaques or to the superficial intimal erosion, both of which may be followed by coronary thrombosis.(60) Many patients with acute myocardial infarction have multiple complex unstable plaques that are associated with adverse clinical outcomes, thereby suggesting that inflammation may have widespread effects throughout the coronary vasculature . (61) Pathophysiology of Chronic Ischemia:-Chronic ischemia, including stable angina, is classically caused by supply and demand mismatch, where significant fixed coronary stenosis and/or excess myocardial demand result in ischemia. Precipitants include exercise, eating, cold weather, and emotional stress. The acute coronary syndromes of unstable angina and myocardial infarction are generally caused by a combination of plaque disruption, platelet and thrombin-mediated coronary thrombosis, coronary spasm, and microvascular dysfunction. (62) Of interest is the predilection for these episodes to occur in the early morning or shortly after arising. Antithrombotic therapy is directed toward inhibition of platelet activity (aspirin, clopidogrel, glycoprotein GP IIb/IIIa receptor antagonists), inhibition of coagulation (unfractionated or low-molecular-weight heparin, fondaparinux, bivalirudin), and fibrinolysis for ST-segment elevation myocardial infarction. (62)Some episodes of myocardial ischemia are symptomatic, causing angina pectoris; others are completely silent. Many silent episodes are brought on by emotional and mental stress. In patients with diagnosed coronary disease, as evidenced by prior myocardial infarction or angina, silent ischemic episodes have the same prognostic import as symptomatic ones. The prognosis for patients with only silent ischemia is not well established, nor is the potential benefit


of preventing silent ischemia. (63) Exposure of thrombogenic plaque material to flowing blood initiates the endogenous thrombotic response. Actual plaque rupture may precede the clinical syndrome of ACS by several days or even weeks, as evidenced by findings of both fresh and old thrombus in samples of coronary aspirate. (64) The other mechanism in the pathophysiology of IHD is coronary spasm. At least three independent predictors of risk are valuable in anticipating increased incidence of atherosclerosis; hypelipidemia, cigarette smoking, and hypertension. (65) Recognised factors which put a plaque at risk are a large lipid core, a thin friable cap, high macrophage density and reduced smooth muscle cell content. Macrophage derived tissue factor found in abundance in the lipid rich core of the plaque is largely responsible for its intense thrombogenicity. The integrity of the fibrous cap overlying this lipid rich core however determines the stability of the plaque. Rupture-prone plaques have thin friable caps which when torn, exposes the thrombogenic substrate to circulating blood and, in the presence of other prothrombotic factors, lead to thrombus formation. Different degrees of thrombus formation over the fissured plaque manifest in a spectrum of conditions. (66) In its mildest form, minor intralesional platelet thrombus may be associated only with the intimal layer and contribute to plaque growth by stimulating further thrombin-mediated smooth muscle cell proliferation.Subclinical thrombosis plays an important part in the development of chronic stenoses that gives rise to stable angina. In an autopsy study of patients with coronary atheroma who died of sudden noncardiac causes, 17% had small recent plaque disruption with thrombus within the lipid core. Subjects who died of major plaque disruption had on an average, 2.5 smaller plaques elsewhere with evidence of minor disruption and thrombosis(66) . Risk Factors:- According to projections for the year 2020, cardiovascular disease (CVD) will remain as the major cause of mortality and disability. Currently, developing regions more greatly contribute to the CVD burden than developed ones . Such rise in CVD within developing regions may result from the following 3 factors: a decrease in mortality due to parasite infections, with an increase in life expectancy; lifestyle and socioeconomic changes associated with urbanization, resulting in higher levels of CVD risk factors; and special susceptibility of certain populations (due to specific genes), leading to a greater impact on clinical events when compared with populations from developed western regions (67) . Acute myocardial infarction (AMI) has a high rate of morbidity and cost of hospitalization, long term disability and


mortality. Published data from United States showed that the mortality rate due of myocardial infarction (MI) decreased in the decade of 1960’s. The decreasing rate was 54% during 1963-90 and it reached 31% during 1982 to 1990. This decreasing rate was mainly due to prevention of major risk factors by community based intervention programs(68) .However, there is little comparative data available about the rates of occurrence, risk factors and mortality of CAD among Arabs living in Middle Eastern countries(24) . The dramatic decline in cardiovascular disease in developed countries during the past 40 years is primarily due to the optimal intervention of traditional risk factors such as cigarette smoking, elevated total and low density lipoprotein (LDL) cholesterol, elevated blood pressure, low high-density lipoprotein (HDL) cholesterol, and diabetes mellitus . (69) However, many of these patients continue to have cardiac events due to the emergence of other non-traditional predisposing factors such as psychosocial stress. Psychosocial stress worsens the risk associated with the traditional risk factors and contributes to mechanisms underlying cardiac events, especially endothelial dysfunction, myocardial ischemia, plaque rupture, thrombosis, and malignant arrthymias.(70)In epidemiologic studies, the major classical risk factors were documented very well and it was clearly known that hypertension, hypercholesterolemia, diabetes mellitus, smoking and familial history increase the risk of MI (71) . Basic and clinical studies have clearly shown the biological relation between these risk factors and atherosclerosis. Published studies showed different results on changing pattern of cardiovascular risk factors in different societies (72). Myocardial infarction (MI) is the leading cause of mortality and morbidity in both developed (73) and developing countries.(74) Recognition of risk factors in different groups of people may significantly affect prevention strategies and can be especially very useful in the younger ages. Risk factor profiles vary in different ethnic groups (75) . Differentiating acute coronary syndrome from noncardiac chest pain is the primary diagnostic challenge. The initial assessment requires a focused history (including risk factor analysis), a physical examination, an electrocardiogram (ECG) and, frequently, serum cardiac marker determinations (76). Unmodifiable risk factors for cardiovascular disease include age, male sex, and family history. The effect of race is unclear, although most high quality evidence that adjusts for differences in baseline risk factors suggests that cardiovascular mortality, and the relative risks from modifiable risk factors, are similar across ethnic groups .(77)


According to epidemiological characteristics, percentage of morbidity, early disability and mortality, ischemic heart disease represents a very serious sociomedical problem in the majority of countries. Data from the World Health Organization show that there is an increase in the morbidity and mortality due to ischemic heart disease. In the USA and some other western countries, a drop in the rate of ischemic heart disease has been recorded due to a large-scale campaign for reduction of risk factors. Age and Sex :- Age may be the only major risk factor that does not cause CHD by directly promoting atherosclerosis. However, accumulation of atherosclerotic plaques in CHD progresses over time, and the probability of developing an adverse coronary event is a function of the total coronary plaque burden. (78) Thus, increased age increases the risk of developing more severe CHD. Most new-onset CHD in both men and women occurs after the age of 65 years, and almost 85 percent of all deaths due to CHD are recorded among people 65 years of age and older. Although the risk of developing CHD is much higher among men than in women until they reach around 60 years of age, this relationship changes after menopause, when the risk increases rapidly in women so that it equals that of men(78) .Going through menopause may increase the rate of CHD in women, so that a menopausal or postmenopausal woman has a risk two to three times higher than that of a pre-menopausal woman of the same age. (79) Older people have a higher risk of dying when they have an ischemic cardiac event. The fatality rate for men before the age of 50 years who had no pre-existing MI or stroke 19 Background THE CLINICAL PRESENTATION OF ACUTE CORONARY SYNDROME-ALGAMHORIA HOSPITAL -ADEN was 20 percent, while men aged 65 to 69 years had a mortality rate of more than 50 percent, which increased to up to 80 percent in those older than 70 years of age.(79) There are several clinically important differences between men and women. Although the incidence of acute myocardial infarction (AMI) increases sharply with age, women are less prone to develop AMI than men at any given age, with a lag of approximately 9–10 years between the sexes.(80). The difference in mortality and morbidity diminishes with age, but even between the ages of 75 and 85 years the incidence is almost twofold greater in men than in women.(81) The difference in age seems to be less pronounced for non-ST-elevation AMI (82).and may be still smaller for unstable angina (83). Within the past decade three meta-analyses have produced conflicting results.(84) Two concluded that women with diabetes were at increased risk of mortality from coronary heart disease compared


with men, whereas the third found no difference. These discrepancies may have arisen from differences in the level of adjustment for other cardiovascular risk factors between included studies. For example, as lipid levels are directly affected by diabetes, and to differing degrees in men and women (85). There is a growing body of evidence that women commonly experience ischemia in the absence of obstructive CAD. The majority of this data comes from the WISE (Women’s Ischemia Syndrome Evaluation) study, WISE Investigators found that over half of the women they tested had evidence of endothelial dysfunction and/or microvascular disease despite the majority of them having no or minimal epicardial disease.(86)In addition, the presence of these vascular derangements was associated with future cardiovascular events, including congestive heart failure(CHF), MI, stroke, and death even after controlling for the degree of CAD and multiple cardiac risk factors. (86) Family History:- Family history of heart disease has been associated with the risk of coronary heart disease(CHD) in several studies,(87)Family history of CHD is associated with each of the following stages in the development of the disease in probands: risk factor elevation (88) ,subclinical atherosclerosis (89), and clinically manifested CHD (90) . Aggregation of the major risk factors present in families does not totally account for the within-family aggregation of CHD. Furthermore, occurrence of CHD in families usually does not follow the pattern of simple Mendelian inheritance, leading to the aphorism that CHD aggregates but does not segregate within families. Inheritance of increased susceptibility to CHD results from the intergenerational transmission of cultural, lifestyle, and shared environmental determinants of CHD . (91) As well as multiple susceptibility genes. Parental socioeconomic status is a strong determinant of the adult socioeconomic status of offspring, and CHD-relevant lifestyle, behavioral, dietary, and smoking practices may thereby aggregate within families and be expressed as adult CHD risk (92). A large number of genes associated with increased risk of CHD have been identified, generally by their relation to the known risk factors. For example, numerous biochemical steps in the metabolism of serum lipids (93) and physiologic steps in the regulation of blood pressure (94) are known to be influenced by genes and therefore influence CHD risk. Thus, although a few genetic disorders of large, single gene effects exist, such as familial hypercholesterolemia, CHD and its major risk factors generally involve many genes, each having a relatively small effect.


Regarding lipids, for example, lipoprotein receptors, apolipoproteins and Upases, and structural and functional gene product proteins have been identified as influencing each of the large number of biochemical steps involved in absorption of dietary fatty acids and cholesterol and in synthesis, transport, and metabolism of serum lipoproteins. Numerous mutant alleles have been found for genes identified to date. (95) Given the large number of susceptibility genes and their mutant alleles, each responsible for only a small effect, and the general modification of genes' effects in different environments and in the presence of other genes, CHD is classified as a complex genetic disorder. Gene-by-environment and gene-by-gene interactions invalidate meaningful attempts to estimate the relative importance of genes versus environment or the independent effect of a single gene or single risk factor under all circumstances. Multiple interdependent steps are involved in maintenance of physiologic and biochemical homeostasis of levels of the risk factors and mediators. Although each step is influenced by the genotype, mapping of the susceptibility genotypes to risk factor levels and to subclinical and clinical CHD phenotypes, modified as they are by internal and external environments, presents formidable theoretical and methodological challenges . (95) Smoking :- The relationship between tobacco use and CVD is well known. It is estimated that 4 million deaths from tobacco occurred in 1999 and that the annual number of deaths is likely to rise to 10 million by 2030. The WHO predicts that tobacco deaths in India may exceed 1.5 million annually by 2020. Cigarette smoking increases the risk of CVD death by 70 % compared with not smoking (96). Tobacco use is a growing health concern in the developing world, particularly in places where disposable income is increasing (97).Smoking prevalence has increased in adolescents since 1991 even though there has been a decline in the overall prevalence of smoking in many industrialized countries (98). According to the most recent estimate by the World Health Organization, 4.9 million people worldwide died in 2000 as a result of their addiction to nicotine, about half of them prematurely (99).Developing countries already account for half of all deaths attributable to tobacco. The proportion will rise to 7 out of 10 by 2025 because smoking prevalence has been increasing in many low-income and middle-income countries while it is falling in richer countries, especially among men (100). Another study on smoking and mortality from tuberculosis and other diseases in India showed that the death rates from medical causes of ever-smokers were double those of never smokers (101) . In Saudi Arabia, Al Khadra found that smoking


was the main risk factor for having acute myocardial infarction at a young age (< 45 years), followed by low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and diabetes (102). The risk of cardiovascular disease in smokers is proportional to the number of cigarettes smoked and how deeply the smoker inhales, and it is apparently greater for women than men. (103) The adverse prognostic effects of smoking may relate not only to the increased risk of developing atherosclerosis but also to the increased risk of occlusive thrombosis and myocardial infarction. Indeed, in young patients, cigarette smoking has been associated with thrombotic coronary occlusion even in the absence of angiographic atherosclerotic disease (104). Cigarette smoking is assumed to promote the buildup of coronary plaques, destabilize coronary plaques, promote plaque rupture, increase platelet activation and cause endothelial dysfunction, all of which consequently cause coronary thrombosis. Furthermore, smoking increases catecholamine release and may cause coronary spasms. Not surprisingly, smoking is a significant risk factor for angina pectoris and MI. Smoking cessation is associated with reduced risk of experiencing MI, eradicating the risk associated with smoking as soon as about two to three years after cessation(105). Hypertension :- Hypertension affects nearly 26 per cent of the adult population worldwide (106). Hypertension is an important independent predictor of cardiovascular disease, cerebrovascular accidents and death (107). The prevalence of cardiovascular diseases and hypertension is rapidly increasing in developing countries (108). This increase, most marked in the urban population, is likely to be related to changing life-styles and to an increased longevity. Cardiovascular diseases are estimated to have led to 1.59 million deaths in India in the year 2000 and this figure is projected to increase to 2.03 million for the year 2010(109). Hypertension has been reported to be responsible for 57 per cent of all stroke deaths and 24 percent of all cardiovascular deaths in East Asians(110) The number of adults with hypertension in 2025 was predicted to increase by about 60% to a total of 1.56 billion (1.54-1.58 billion)(111) .Uncontrolled hypertension is a major health concern in the United States. It causes various illnesses associated with a high incidence of morbidity and mortality, including end-stage renal disease, stroke and CHD,Several clinical trials have suggested that lowering of blood pressure will reduce the risk of developing CHD . (112) Hypertension is a major contributor to atherosclerosis-induced cardiovascular disease (113). The prevalence is higher in men than in women below the age of 35 years


but by the age of 65 years the prevalence is higher in women (114). In elderly women, it is the single most important risk factor for cardiovascular disease . (115) Data available from several Eastern Mediterranean countries indicate that hypertension is emerging as an important cause of morbidity and mortality. Epidemiological surveys on hypertension report a prevalence of 20% to 26% in the adult population (116). In some urban areas high blood pressure may affect up to 30% of the adult population (117). The prevalence of hypertension appears to be lower in rural than in urban areas (118).One important feature of hypertension is being asymptomatic until target organ damage has ensued, at which time intervention is already too late . (119) The main mechanism of action through which hypertension leads to the development of atherosclerosis is mechanical damage to endothelial cells due to altered hemodynamics, i.e. enhanced force of the blood flow, or to the formation of whirls at vascular bifurcations . (120) Hypercholesterolemia:- Regarding Hypercholesterolemia epidemiological studies show that there is a direct relationship between the level of serum total cholesterol and low density lipoprotein with the rate of coronary heart disease (121).Many studies showed that 80-90% of CAD patients had one of four classical risk factors such as hypercholesterolemia, hypertension, diabetes mellitus and smoking (122), Hypercholesterolemia is a recognized reversible risk factor for CHD. This has been shown in several studies in which cholesterol and mortality rate have a close linear relationship. (123) Accordingly, recommendations on cholesterol screening suggest that all adults aged 20 years and older should have a fasting lipoprotein profile (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides) performed every five years. (124) Although the risk of developing CHD is very low when the serum LDL cholesterol level is below 100 mg/dL, atherogenesis occurs even at the near-optimal level of a LDL cholesterol of 100 to 129 mg/dL,Combination of several risk factors usually provides a more comprehensive picture of the overall risk. Thus, men aged 45 to 65 years are at an increased risk of developing CHD when their total serum cholesterol level is < 240 mg/dL and/or their LDL cholesterol levels are > 160 mg/dL. The risk of developing CHD is threefold in a middle-aged man who has LDL cholesterol levels > 160 mg/dL and two additional risk factors as compared with a man the same age who has a lower level of serum LDL cholesterol (125)Low serum HDL cholesterol also is strongly associated with an increased risk of developing CHD. (126) It has been proposed that HDL attenuates the atherogenicity of LDL, which would result in increased atherogenesis at low serum HDL levels.


Furthermore, HDL also may be a marker for both an insulin-resistant state and the presence of other atherogenic lipoproteins, such as very low-density lipoproteins, which have been associated with the development of CHD. (127)While low HDL levels are considered a major risk factor for CHD, high levels may be protective. Recent data demonstrated a significant reduction in major cardiovascular events when HDL levels were raised . (128) Diabetes mellitus:-Diabetes mellitus is a major contributing factor in the development of CHD(129). The problem with diabetes is that it increases the morbidity and mortality due to the propensity to develop micro and macro angiopathy. Of all the complications that be set diabetic subjects, the most dangerous and life threatening is CAD. Diabetic subjects have two or more fold higher risk for CAD compared to non-diabetic population (130). Despite the wide geographical variation in the prevalence of diabetes and CAD, the association of these two remains strong. Irrespective of the ethnic background, diabetic subjects have been shown to have high risk for CAD compared to the non-diabetic population . (131) Diabetes mellitus affects 6% of the US population but is present in as many as 30% of patients hospitalized with acute coronary syndromes. It has been recognized for some time that diabetics experience a greater mortality during the acute phase of myocardial infarction (MI) and a higher morbidity in the post infarction period . (132) It is well known that coronary artery disease (CAD) is strongly associated with diabetes mellitus (DM). It increases the risk of coronary artery disease (CAD) by twofold to six fold, which account for 80% of deaths among patients with DM. (133) Furthermore, when CAD develops in diabetic patients, the incidence of acute coronary syndrome (ACS) becomes double (133). Since diabetic patients have an increased propensity for blood clotting, impaired fibrinolysis and increased platelet reactivity, it is more likely that atherosclerotic plaque rupture or erosion results in thrombotic occlusion of the artery .(134) Overall 20-35% of all ACS patients are diabetic .(135) In addition to being a risk factor, diabetes mellitus is also associated with worse outcome after an acute coronary event. (136) Diabetes has been confirmed to be an independent risk factor for the occurrence of coronary disease. The link between diabetes and coronary disease has been known for some 70 years . (137) Obesity:- Obesity also play important role, More than 43 million Americans older than 20 years of age are obese, based on a body mass index, or BMI, of 30.0 or higher. (The BMI is calculated by dividing weight in kilograms by height square in


meters (138)) Obesity is the major factor associated with insulin resistance and the metabolic syndrome, and it is considered the number 1 factor predisposing Americans to develop CHD. In addition, a strong association has been found between overweight that begins in childhood and a progressive increased rate of developing other risk factors during adulthood. (139) The cause of overweight and obesity in the United States is, for the most part, an excessive intake of food and sedentary life habits. BMI approximates total body fat, but fat distribution may be an adjunct predictor of CHD. Waist circumference gives a better indication of the degree of insulin resistance, and fat deposit around the waist appears more significant than fat accumulation at other sites in the development of CHD, Consequently, waist circumferences of more than 40 inches in men and more than 36 inches in women suggests significant insulin resistance and a high risk of developing CHD (140). Accordingly, the American Heart Association has proposed that obesity should be included as a major risk factor for CHD (141). Furthermore, obesity often coexists with other CAD risk factors, such as hypertension, dyslipidemia and diabetes (142). Some investigators have shown that obesity is a CAD risk factor in Asia as well as in Western countries (143). Body weight and incidence of cardiovascular disease are positively associated in both sexes after adjustment for other risk factors, but obesity is a more potent risk factor in women than men and in younger than older people(144). Physical inactivity:- Physical inactivity is a common modifiable risk factor for CAD (145),and is associated with at least a two fold increase in the risk of coronary events. Current recommendation is regular physical exercise both as primary and as secondary measure. Habitual exercise diminishes the risk of sudden death(146) even further ,Exercise has beneficial effects on weight control and several other important cardiovascular risk factors such as: lipid profile, blood pressure, DM type2 (147).Exercise increases HDL, reduce LDL and TG, increase insulin sensitivity and reduce resting blood pressure . (145) psychological factors:-Psychological factors, such as emotions, may also have a role in the development of coronary heart disease. Several prospective studies have found anxiety, hostility/anger, and depression to be associated with an increased risk of coronary heart disease in healthy participants. As the relative importance of these three negative emotions on risk of coronary heart disease remains largely undefined (148). Khat(Catha Edulis):- Khat, sometimes spelled as qat, is the Arabic name for Catha Edulis, an evergreen shrub or tree that


grows up to 10 meters in height. Khat is a central nervous system stimulant like coffee, tea, cocoa, cola, coca, tobacco, cocaine, and amphetamines. Natives of Eastern Africa, the Arabian Peninsula, and the Middle East have used Khat as a recreational and religious drug since antiquity. Its use is legal in many countries including Britain. Although khat can be abused, it is often used in a social context similar to the manner in which coffee is consumed in other parts of the world. Khat chewing is a common and widespread practice in Yemen. Reports from Yemen indicate that khat is consumed by 3 out of every 4 Yemenis, and accounts for more than40 percent of the average family budget. Khat has been blamed for many social, health, and economic problems in Yemen(149). Khat represents a real medical problem. There are few clinical studies linking khat-chewing and diseases in different organ systems. Khat-chewing has been suggested in modifying the circadian rhythm in acute myocardial infarction This is may be due to its effect on increasing blood pressure and heart rate. These effects may precipitate AMI, just like amphetamine. Since khat chewers like closed and warm rooms, the habit promotes active and passive smoking, and lack of physical activity. It also causes nervous tension, lack of concentration, irritability and Insomnia. There are three main alkaloids present in khat leaves: Cathinone, cathine and ephedrine1.Cathinone is the main active substance in khat leaves. Cathinone is amphetamine-like substance that release endogenous catecholamines from peripheral and central neurones. Cathinone major metabolites are norpseudoephedrine and ephedrine. These two substances have weaker sympathomimetic activities and central stimulant properties. Cathinone is responsible for the CNS effect of khat while norpseudoephedrine is responsible for its peripheral effects ,Khat chewing changes the circadian rhythm of acute MI presentation where most of the chewers had their heart attack during the khat effective period [1200-2400 hours.] and was an independent dose-related risk factor for acute myocardial infarction(149). Accurate diagnosis of acute coronary syndrome should begin with careful history taking and physical examination, with particular emphasis on categorization of a patient's level of risk. In conjunction with electrocardiographic and laboratory data, each patient with chest pain can be stratified into groups of high, intermediate, or low risk according to guidelines established by the American College of Emergency Physicians and the Agency for Health Care Policy and Research(150). Diagnosis:- Although the formal diagnosis of AMI requires documentation of elevated cardiac biomarkers (151), time delays in biomarker elevation limit their


usefulness in early decision making. For this reason, initial diagnostic and treatment decisions rely primarily on clinical features and electrocardiogram (ECG) findings. Time of symptom onset is important, as it affects management options. Symptom onset within 12 hours is the generally accepted window of eligibility for fibrinolytic therapy (152). Ischemic symptoms are often described as Typical (with chest pain) or atypical (without chest pain), Although it is frequently assumed that a typical presentation is more commonly associated with ECG changes, (153). About 15% of patients who present to the emergency department on account of chest pain have an acute MI, while 35% have unstable angina (154). The degree to which a coronary artery is occluded typically correlates with presenting symptoms and with variations in cardiac markers and electrocardiographic findings. Angina, or chest pain, continues to be recognized as the classic symptom of ACS. (155) In unstable angina, chest pain normally occurs either at rest or with exertion and results in limited activity. Chest pain associated with NSTEMI is normally longer in duration and more severe than chest pain associated with unstable angina. (155) In both conditions, the frequency and intensity of pain can increase if not resolved with rest, nitroglycerin, or both and may last longer than 15 minutes. Pain may occur with or without radiation to the arm, neck, back, or epigastric area.(155)In addition to angina, patients with ACS also present with shortness of breath, diaphoresis, nausea, and lightheadedness. Changes in vital signs, such as tachycardia, tachypnea, hypertension, or hypotension, and decreased oxygen saturation (SaO2) or cardiac rhythm abnormalities may also be present. (155) Many women present with atypical symptoms, resulting in delayed diagnosis and treatment . (156) Women frequently experience shortness of breath, fatigue, lethargy, indigestion, and anxiety prior to an acute MI and may not attribute those symptoms to heart disease. (157) It's also important for clinicians to realize that women tend to experience pain in the back rather than substernally or in the left side of the chest and do not characterize it as pain, but may instead report a numb, tingling, burning, or stabbing sensation (158); in fact, a recent study found that, when compared with men, women diagnosed with ACS more often reported indigestion, palpitations, nausea, numbness in the hands, and atypical fatigue than chest pain. (159) Ischemia can also occur without any obvious signs or symptoms (Silent ischemia). Populations more likely to experience a silent MI include people with diabetes, women, older adults, and those with a history of heart failure. (152) Any patient with a


history suggestive of acute coronary syndrome should be evaluated in a facility that has ECG and cardiac monitoring equipment. Patients with suspected acute coronary syndrome who have chest pain at rest for more than 20 minutes, syncope/presyncope, or unstable vital signs should be referred to an emergency department immediately.(160)The diagnosis of acute myocardial infarction, which includes both STEMI and NSTEMI, requires at least two of the following: ischemic symptoms, diagnostic ECG changes, and serum cardiac marker elevation. (161) Electrocardiographic findings:-. The AHA and the ACC recommend that a 12-lead electrocardiogram (ECG) be performed in patients with symptoms consistent with ACS and interpreted by an experienced physician within 10 minutes. (155) Findings on a 12-lead ECG help the practitioner to differentiate between myocardial ischemia, injury, and infarction; locate the affected area; and assess related conduction abnormalities. Electrocardiographic findings reflective of unstable angina or NSTEMI include ST-segment depression and inverted T waves. ST depression will normally resolve when the ischemia or pain has resolved, although T-wave inversion may persist. Providers should review electrocardiographic findings as well as levels of cardiac biomarkers to distinguish between unstable angina and NSTEMI. (155) On the other hand, ST elevation on a 12-lead ECG in two contiguous leads is diagnostic of STEMI. With STEMI, T-wave inversion may also be present. These changes normally subside within hours of an MI. Abnormal Q waves appear on an ECG in the presence of an MI as a result of alterations in electrical conductivity of the infarcted myocardial cells. Once an abnormal Q wave has developed it usually remains permanently on the ECG. Therefore, an abnormal Q wave on an ECG does not necessarily signal a current acute MI, but could indicate an old MI. (162) Although the ECG has a sensitivity of only 73% for the diagnosis of acute myocardial infarction (AMI) (163), it has been shown to be more diagnostically useful than biochemical markers in the first 6 hours after chest pain(164) Exercise ECG:- A formal exercise tolerance test(ETT)is usually performed using a standard treadmail or bicycle ergometer protocol to ensure a progressive and reproducible increase in workload while monitoring the patient's ECG (preferably all 12 leads),blood pressure and general condition .Exercise testing can be used to confirm or refute a diagnosis of angina and a useful means of assessing the severity of coronary disease .(165)(It is used in a special conditions and not routinely) Echocardiography:-Among the cardiac imaging techniques employed to evaluate coronary heart disease,


Echocardiography has covered a primary role since the beginning of its application. (166)All the different technologies of echocardiography, from M-mode to the most recent technical developments, have been extensively used in the diagnostic and prognostic evaluation of acute and subacute myocardial infarction. (166) Two-dimensional echocardiography has been very valuable in defining the region and extent of infarction (167) and in predicting complications on the basis of this analysis. (168) Myocardial ischemia frequently causes left ventricular wall motion abnormalities that can be seen easily by echocardiography. Echocardiographic findings precede electrocardiographic abnormalities and angina. Presence and severity of myocardial dysfunction can be documented rapidly, so that echocardiography is an important modality for risk stratification in the emergency room . Echocardiography is a useful tool in the prognostic evaluation of myocardial infarction . Left ventricular angiography may not be appropriate in critically ill patients. Therefore, echocardiography is implemented in the guidelines concerning management of patients with acute coronary syndromes (169). Left ventricular ejection fraction (LVEF) remains one of the most important predictors of an adverse outcome among AMI survivors and therefore is an essential parameter to assess before the patient leaves hospital. A number of studies have provided convincing data for the use of echocardiography and nuclear imaging to determine left ventricular dysfunction and residual myocardial ischaemia postAMI, allowing for earlier, more aggressive treatment in patients with abnormal findings. (170) Stress echocardiography:-The hallmark of myocardial ischaemia during stress echocardiography is the occurrence of reduced systolic wall thickening.This precedes chest pain and ST-T wave changes, which makes stress echocardiography more sensitive than exercise treadmill electrocardiogram (ECG) testing. Rest and stress images are interpreted for global and regional left ventricular size, shape and function. Stress echocardiography can identify the site of coronary stenoses. The total amount of myocardium in jeopardy predicts risk and prolonged persistence of a systolic wall thickening abnormality may also identify severe coronary artery disease. (171) coronary angiography:- The safety and diagnostic potential of coronary angiography during the early hours of acute myocardial infarction have been reported more than 20 years ago. In addition to being a prelude to angioplasty, acute coronary angiography offers several advantages. Patient management after the acute event is facilitated by the knowledge of the coronary anatomy, and allows identification of a large subgroup of patients


that can be discharged very early (2–3 days) after the acute event, as well as the 5–10% of patients who have an indication for elective coronary artery bypass grafting on anatomical grounds, such as left main disease and/or triple vessel disease with involvement of the proximal left anterior descending coronary artery. Some patients presenting with symptoms and signs of acute myocardial infarction should not undergo reperfusion therapy and this can only be ascertained by angiography for example, patients with spontaneous reperfusion of the infarct related coronary artery, or patients with a cardiac event without thrombotic occlusion of a coronary artery or non-cardiac condition, that may mimic acute myocardial infarction. (172) Serum Cardiac Markers:- Injured myocardial cells release proteins and enzymes known as cardiac biomarkers into the blood. These markers help practitioners to determine whether the patient is having or has recently had an acute MI (either an NSTEMI or a STEMI). The utility of various biomarkers is determined by the timing and duration of their elevation as well as by the extent of their cardiac specificity. 1)Troponin:-troponin T and troponin I, are the most cardiac-specific biomarkers. These structural proteins are not normally found in serum; therefore elevated serum levels may predict the degree of thrombus formation and microvascular embolization associated with coronary lesions. Levels of troponins I and T increase within four to six 36 Background THE CLINICAL PRESENTATION OF ACUTE CORONARY SYNDROME-ALGAMHORIA HOSPITAL -ADEN hours of myocardial injury; troponin I levels remain elevated for four to seven days, and troponin T levels remain elevated for 10 to 14 days. Normal reference ranges for cardiac biomarkers vary among laboratories; in order to diagnose myocardial necrosis a single troponin elevation greater than the 99th percentile of an agreed-upon reference control group is required. (173) 2) creatine kinase: The serum CK level rises within three to eight hours after myocardial injury, peaks by 12 to 24 hours, and returns to baseline within three to four days.(174) CK-MB typically is detectable in the serum four to six hours after the onset of ischemia, peaks in 12 to 24 hours, and normalizes in two to three days. The CK-MB mass assay is more sensitive than the CK-MB activity assay.(175)CK-MB may be further characterized into subforms (or isoforms). CK-MB2 is found in myocardial tissue, and CK-MB1 is found in plasma. The CK-MB subform assay takes about 25 minutes to perform.21 A CK-MB2 level greater than 1 U per L in combination with a subform ratio greater than 1.5 suggests myocardial injury. (176) 3) Myoglobin: a hemeprotein, is not cardiac specific, yet it's


still considered a valuable biomarker because it's the first to rise after myocardial damage. If a patient presents with ACS symptoms that started less than three hours earlier, CK-MB and troponin levels may not yet be elevated. In such a case, myoglobin can rule out or lead to an early diagnosis of acute MI and prompt decisive therapy. (173) Time changes in the myoglobin value also can be extremely helpful. Combining a doubling of the baseline myoglobin level at two hours after symptom onset with an abnormal myoglobin test at six hours after symptom onset increases the sensitivity to 95 percent at six hours. (177) 4) lactate dehydrogenase: In a typical patient with acute myocardial infarction serum LDH activity exceeds the normal range within 24 to 48 hours, reaches a peak elevation of two- to tenfold in 3 to 6 days, and declines to the normal range within 8 to 14 days. Following acute myocardial infarction increased serum LDH activity frequently precedes increased total LDH and, in fact, is typically present in the first available blood sample obtained from patients hospitalized for acute myocardial infarction. (178) 5)Aspartate aminotransferase:- starts to rise about 12 hours after infarction and reaches a peak on the first or second day, return to normal within 3 or 4 days. (165) Serum cardiac marker determinations play a vital role in the diagnosis of acute myocardial infarction. Serum markers such as aspartate transaminase, lactate dehydrogenase, and lactate dehydrogenase subforms no longer are used because they lack cardiac specificity. (161) 6)C-Reactive Protein:-The circulating concentration of human C-reactive protein (CRP), the classical acute phase protein, is always increased after acute myocardial infarction, starting within4–6h of the onset of symptoms and reaching a peak after~50h (179).This peak value is associated with outcome, both early and late. Ventricular rupture occurs only in patients with peak serum CRP levels >200mg/liter. (180)and high CRP levels predict mortality over the next 6 month from all causes related to myocardial infarction (181) CRP is found deposited on myocardial cells within the infarcted area, together with activated complement (182) (CRP) is an acute phase reactant marker for underlying systemic inflammation. CRP has been reported to be elevated in patients with acute ischemia and MI. Furthermore, elevated CRP along with other acute phase reactants and cytokines with a focal predominance of inflammatory cells have been found in patients with unstable coronary syndromes . (183) Other blood tests:- Links between anemia and inflammation, or similar, likely synergistic impact of leukocytosis or erythrocytosis on pathophysiological mechanisms associated with adverse clinical course of ACS suggest that


there is a potential interaction between WBC count and Hb and outcomes of ACS . (184) Evaluation of Patients with Chest Pain or Symptoms Suggesting ACS:- No assessment protocol or constellation of tests is totally accurate in diagnosing acute coronary syndrome. From 1 to 4 percent of patients ultimately proven to have acute coronary syndrome are sent home from the emergency department.(185) Rapid diagnosis and early risk stratification of patients presenting with acute chest pain are important to identify patients in whom early interventions can improve outcome. On the other hand, when the diagnosis of acute myocardial infarction has been ruled out, attention can be focused on the detection of other cardiac or non-cardiac causes of the presenting symptoms. (186) Determined of Features associated with high-risk, intermediate-risk and low-risk:- High risk:- *Prolonged (>20 min) ongoing chest pain at rest. *Pulmonary edema, most likely related to ischemia. *Angina at rest, with dynamic ST-segment changes >1 mm. *Angina with new or worsening mitral regurgitant murmur. *Angina with S3 or new or worsening rales. *Angina with hypotension (A patient must have at least one of the features described). Intermediate risk:- *Prolonged (>20 min) angina at rest, now resolved, with moderate or high likelihood of coronary artery disease. *Angina at rest (>20 min or relieved with rest or sublingual nitroglycerin). *Nocturnal angina. *Angina with dynamic T-wave changes. *New-onset Canadian Cardiovascular Society class III or IV angina in the previous 2 week, with moderate or high likelihood of coronary artery disease. *Pathologic Q waves or ST-segment depression <1 mm in multiple lead groups (anterior, inferior, lateral) at rest. *Age >65 year. (A patient must have at least one of the features described and no high-risk features.). Low risk:- *Increased frequency, severity, or duration of angina. *Angina provoked at a lower threshold. *New-onset angina with onset 2 week to 2 month before presentation. *Normal or unchanged electrocardiogram. (A patient must have at least one of the features described and no high-risk or intermediate-risk features) (76). A suggested approach to the evaluation of patients with chest pain or symptoms consistent with acute coronary syndrome is provided in following Figure. (37) patient presenting with chest pain or symptoms consistent with ACS Risk stratification Intermediate risk High risk Low risk


chest pain unit protocol; *Monitor the patient for 8to12 hours for recurrent chest pain suggestive of ACS ,with or *Perform serum cardiac marker determinations (troponin T or I without ck-MB)on admission. *Consider repeating serum cardiac marker determination in 6-12 hours if initial result are negative and onset of chest pain was less than 6 hours before the evaluation. *Obtain a 12-lead ECG on admission and repeat after 8hours . *Monitor the patient for significant arrhythmias and recurring symptoms. Normal observation period Consider additional cardiac testing (e.g. exercise treadmill test). Abnormal finding Normal finding Discharge the patient after Admit the patient. appropriate treatment, with follow-up in 72 hours. Management of Acute coronary syndromes:- The acute coronary syndromes (ACS) encompass acute myocardial infarction (MI) and unstable angina (UA). Based on electrocardiographic features and cardiac injury markers, approximately 30% to 45% of ACS patients have ST-elevation MI (STEMI) and 55% to 70% have either UA or non-ST-elevation MI (NSTEMI). (187) The distinction between acute myocardial infarction and minimal myocardial injury is of immediate practical importance as emergency reperfusion treatment is indicated for acute infarction but not for the remainder of the acute coronary syndromes. (188) Analgesia:- Adequate analgesia is essential not only to relieve severe distress, but also to lower adrenergic drive and thereby reduce pulmonary and systemic vascular resistance and susceptibility to ventricular arrhythmias. Intravenous opiates (initially morphine sulphate 5-10 mg or diamorphine 2.5-5 mg) and antiemetics (initially metoclopramide 10 mg) should be administered through an intravenous cannula and titrated by giving repeated small aliquots until the patient is comfortable. Intramuscular injections should be avoided because the clinical effect may be delayed by poor skeletal muscle perfusion and a painful haematoma may forming. (5) Aspirin:- Aspirin therapy is one of these interventions. Sustained aspirin therapy reduces the risk of a subsequent event 45 and 70 percent. (189) In recent years, other anti-platelet agents have become available. In the CURE study, clopidogrel plus aspirin prevented recurrent events in patients who had ACS better than aspirin alone.The combination provided a 20 percent relative risk reduction in cardiovascular events. (190) Although aspirin is an irreversible inhibitor of platelet cyclooxygenase, and can inhibit the formation of thromboxane A2 and inhibit platelet aggregation, its effects can be overcome in the presence of potent


thrombogenic stimuli. Nevertheless, the benefits of aspirin are substantial and clearly defined; the antiplatelet trialist collaboration demonstrated a 36% reduction in death or myocardial infarction with antiplatelet treatment (predominantly aspirin) versus placebo in unstable angina trials. (191) Patients should be given 162 to 325 mg of aspirin by mouth (crushed or chewed) as soon as possible after symptom onset, unless contraindicated. Aspirin inhibits platelet aggregation and vasoconstriction by inhibiting the production of thromboxane A2. (192) Clopidogrel:- Data from 2 clinical trials have expanded clopidogrel’s role in STEMI from ancillary therapy in patients undergoing percutaneous coronary intervention (PCI) to a key component of standard fibrinolytic regimens and early treatment plans. (193) Patients were randomized to clopidogrel 75 mg/d (after a loading dose of 300 mg) or placebo for a mean duration of 9 months in addition to aspirin. The primary outcome of cardiovascular death, nonfatal MI, or stroke occurred in significantly fewer clopidogrel than placebo recipients. (194) Further, the onset of these salutary effects was seen as early as 2 hours after therapy initiation . (195) Contraindications are similar to those for aspirin therapy, and clopidogrel should not be administered if coronary artery bypass surgery is planned within the next five to seven days because it increases a patient's risk of bleeding. (155) However, despite its expense, clopidogrel therapy has been shown to be cost-effective for ACS patients over the long-term. Meta-analyses of available pharmacoeconomic studies of clopidogrel suggest that dual antiplatelet therapy with 43 Background THE CLINICAL PRESENTATION OF ACUTE CORONARY SYNDROME-ALGAMHORIA HOSPITAL -ADEN clopidogrel and aspirin is cost-effective when used for up to 12 months in ACS patients and those undergoing a percutaneous coronary intervention PCI. (196) Glycoprotein IIb/IIIa inhibitors:- Glycoprotein IIb/IIIa inhibitors are the antiplatelet agents used in unstable angina and NSTEMI patients who are scheduled for an invasive diagnostic procedure. These drugs bind to the platelet surface integrin glycoprotein IIb/IIIa receptor sites and inhibit the binding of fibrinogen and subsequent platelet aggregation. If PCI is planned and can be performed without delay, the glycoprotein IIb/IIIa inhibitor of choice is abciximab (ReoPro). If the PCI is not planned or is delayed, the glycoprotein IIb/IIIa inhibitors eptifibatide (Integrilin) or tirofiban (Aggrastat) are preferred. These agents may also be considered in patients opting for conservative treatment. Glycoprotein IIb/IIIa inhibitors confer the greatest benefits in patients scheduled for PCI who have elevated cardiac troponin levels. (155) Irrespective of revascularization strategy,


evidence supports the use of glycoprotein IIb/IIIa inhibitors in those with recurrent or refractory ischaemia (despite heparin and aspirin treatment) and in whom intervention is delayed or contraindicated. (191) Heparin :- Unfractionated heparin is widely used in the management of patients with unstable angina or minimal myocardial injury, although the evidence supporting its use in the absence of aspirin treatment is less robust than in the presence of aspirin. Maintaining accurate antithrombin control with unfractionated heparin is unpredictable because of plasma proteins binding, including that induced by acute phase proteins. There is reduced effectiveness in the presence of platelet rich and clot bound thrombin. Trials have also been conducted of low molecular weight heparin versus unfractionated heparin and two of these trials (ESSENCE and TIMI 11b, both using enoxaparin) have indicated superiority, with an absolute reduction of 30 events per 1000 patients treated (death/myocardial infarction/refractory angina). These benefits are seen without excess major bleeding but with some increase in minor bleeding including bruising at puncture sites. (191) Thrombolytic therapy:- Streptokinase is antigenic and occasionally causes serious allergic manifestations. It may also cause hypotension, Circulating neutralising antibodies are formed following treatment with streptokinase and may persist for 5 years or more. These antibodies can render subsequent infusions of streptokinase ineffective so it is advisable to use another non-antigenic agent if the patient requires further thrombolysis in the future.Alteplase, (human tissue plasminogen activator or tPA) is a genetically engineered drug that is not antigenic and seldom causes hypotension.There is evidence that tPA may produce better survival rates than streptokinase, particularly among high-risk patients (e.g. large anterior infarct), but with a slightly higher risk of intracerebral bleeding (10 per 1000 increased survival, but 1 per 1000 more non-fatal stroke).Reteplase, (rPA) trial data indicate a similar outcome to that achieved with alteplase. (5) An overview of all the large randomised trials confirms that thrombolytic therapy significantly reduces short-term mortality in patients with suspected MI if it is given within 12 hours of the onset of symptoms and the ECG shows bundle branch block or characteristic ST segment elevation of greater than 1 mm in the limb leads or 2 mm in the chest leads. Thrombolysis appears to be of little net benefit, and may be harmful in other patient groups, specifically those who present more than 12 hours after the onset of symptoms and those with a normal ECG or ST depression. In patients with ST elevation or bundle branch block, the


absolute benefit of thrombolysis plus aspirin is approximately 50 lives saved per 1000 patients treated within 6 hours and 40 lives saved per 1000 patients treated between 7 and 12 hours after the onset of symptoms. (5) The benefit is greatest for patients treated within the first 2 hours. To achieve prompt therapy, patients with suspected myocardial infarction should be assessed as soon as possible. (5)The relative contraindications to thrombolytic therapy (potential candidates for primary angioplasty)are:- (165) 1=active internal bleeding. 2=previous subarachnoid or intracerebral haemorrhage. 3=uncontrolled hypertention. 4=recent surgery(within 1 month) 5= recent trauma.(including traumatic resuscitation. 6=high probability of active peptic ulcer. 7= Pregnancy. Percutaneous coronary interventions (PCI):- The role of percutaneous coronary interventions (PCI) during the early hours of myocardial infarction can be divided into primary PCI, PCI combined with pharmacological reperfusion therapy, and‘rescue PCI’ after failed pharmacological reperfusion. Primary PCI is defined as angioplasty and/or stenting without prior or concomitant fibrinolytic therapy, and is the preferred therapeutic option when it can be performed within 90 min after the first medical contact. It requires an experienced team, which includes not only interventional cardiologists, but also skilled supporting staff.PCI performed as a matter of policy immediately after fibrinolytic therapy, in order to enhance reperfusion or reduce the risk of reocclusion, has proved disappointing in a number of earlier trials all showing a tendency to an increased risk of complications and death. (186) Nitrates: -Nitrates act predominantly by venodilatation and in higher doses by arteriolar dilatation; hence they reduce preload and afterload, thereby decreasing oxygen demand. (191)Nitrates, of course, continue to be first line therapy for angina pectoris. (186) Beta-blockers:- Several trials and meta-analyses have demonstrated that beta-adrenoreceptor blocking drugs reduce mortality and reinfarction by 20–25% in those who have recovered from acute myocardial infarction. (186) Angiotensin-converting enzyme (ACE) inhibitors:- Several trials have established that ACE inhibitors reduce mortality after acute myocardial infarction with reduced residual left ventricular function. (186) In patients with an intolerance to ACE inhibitors, angiotensin-receptor blockers can be considered as alternative therapy. (155) Lipid-lowering agents:- patients should be prescribed lipid-lowering therapy with statins if, in spite of dietary measures, total cholesterol levels of ≥190 mg. (186) Complications of Acute Myocardial Infarction:- 1) Ischemic complications:- Reocclusion of an infarct-related artery (IRA)


occurs in 5% to 30% of patients following fibrinolytic therapy. These patients also tend to have a poorer outcome. (197) 2) Mechanical complications:- *Ventricular Septal Rupture:- VSR formerly occurred in 1% to 2% of patients after acute MI in the prethrombolytic era. The incidence has dramatically decreased with reperfusion therapy. VSR may develop as early as 24 hours after MI but was commonly seen 3 to 7 days after MI in the prefibrinolytic era and 2 to 5 days currently. Fibrinolytic therapy is not associated with an increased risk of VSR. (198) *Mitral Regurgitation:- MR of mild to moderate severity is found in 13% to 45% patients following acute MI. (199) Whereas most MR is transient in duration and asymptomatic, MR caused by papillary muscle rupture is a life-threatening complication of acute MI.Fibrinolytic agents decrease the incidence of rupture; however, when present, rupture may occur earlier in the post-MI period than in the absence of reperfusion. Although papillary muscle rupture was reported to occur between days 2 and 7 in the prefibrinolytic era, the SHOCK Trial Registry demonstrated a median time to papillary muscle rupture of 13 hours. (200) *Free Wall Rupture: - Free wall rupture occurs at three distinct intervals, with three distinct pathologic subsets. Type I increases with the use of fibrinolytics. It occurs early (within the first 24 hours) and is a full-thickness rupture. Type II rupture occurs 1 to 3 days post-MI and is a result of erosion of the myocardium at the site of infarction. Type III rupture occurs late and is located at the border zone of the infarction and normal myocardium. The reduction in type III ruptures as a result of the advent of fibrinolytics has resulted in no change in the overall free wall rupture rate. It has been postulated that type III ruptures can occur as a result of dynamic left ventricular outflow tract obstruction and the resultant increased wall stress. (201) *Left Ventricular Failure and Cardiogenic Shock:- Some degree of left ventricular dysfunction is to be anticipated after an acute MI. The degree of dysfunction correlates with the extent and location of myocardial injury. Patients with small, more distal infarctions may have discrete regional wall motion abnormalities with preserved overall left ventricular function because of hyperkinesis of unaffected segments. (202) *Right Ventricular Failure:- The degree of RV dysfunction depends on the location of the right coronary artery (RCA) occlusion. Only proximal occlusions (proximal to the acute marginal branch) of the RCA result in marked dysfunction. (203) 3) Arrhythmic Complications: - Ventricular arrhythmia is a common complication of acute MI, occurring in almost all patients, even before monitoring is possible. It is related to the formation of re-entry circuits at the


confluence of the necrotic and viable myocardium. (204) Premature ventricular contractions (PVCs) occur in approximately 90% of patients. The incidence of ventricular fibrillation is approximately 2% to 4%. Although lidocaine has been demonstrated to reduce the rate of primary ventricular fibrillation in patients with MI to some extent, there is no survival benefit and there may be excess mortality. Therefore, it is not recommended that patients receive prophylactic therapy. (204) The importance of ventricular fibrillation in the setting of MI has been re-evaluated in the context of the interaction between severe systolic dysfunction and the potential for sudden cardiac death. Implantable defibrillators have been shown to reduce mortality in patients with an ejection fraction (EF) lower than 30%, regardless of the presence of ventricular dysrhythmia. (205) Temporary transvenous pacing is indicated in patients who present with asystole, Mobitz type , or complete AV block. Consideration for transvenous pacing should be given to patients with bifascicular or trifascicular block in the setting of acute MI. (206) 4) Embolic Complications:- The incidence of clinically evident systemic embolism after MI is lower than 2%. The incidence increases in patients with anterior wall MI. The overall incidence of mural thrombus after MI is approximately 20%. Large anterior MI may be associated with mural thrombus in as many as 60% of patients. (207) 5) Pericarditis:- The incidence of early pericarditis after acute MI is approximately 10%. The inflammation usually develops between 24 and 96 hours after MI. (208) Evolving MI changes may mask the diagnosis of pericarditis. Pericarditis produces generalized ST-segment elevation, which is concave or saddle-shaped. As pericarditis evolves, T waves become inverted after the ST segment becomes isoelectric. Conversely, in acute MI, T waves may become inverted when the ST segment is still elevated. Four phases of electrocardiographic abnormalities have been described in association with pericarditis. (209)as in following table;

Stage

Electrocardiographic Change

I ST elevation, upright T waves II ST elevation resolves, upright to flat T waves III ST isoelectric, inverted T waves IV ST isoelectric, upright T waves


Coronary artery disease (CAD) is a well-established major cause of death

and disability in both developed and developing countries (1). Although cardiovascular mortality has been diminishing in Western Europe and North America for the past decades, it is still one of the major contributors to mortality, especially premature death. (2) Regardless of declines in developed countries, both CAD mortality and the prevalence of CAD risk factors continue to rise rapidly in developing countries .(3) About 38% of people who experience an acute coronary event, either angina or myocardial infarction, will die of it in the same year.(4) Coronary heart disease (CHD) is the most common form of heart disease and the single most important cause of premature death in Europe, the Baltic states, Russia, North and South America, Australia and New Zealand. By 2020 it is estimated that it will be the major cause of death in all regions of the world.(5) In the UK (population 59 million), 1 in 3 men and 1 in 4 women die from CHD. An estimated 330 000 people have a myocardial infarction each year and approximately 1.3 million people have angina. The death rates from CHD in the UK are amongst the highest in Western Europe (more than 140 000 people) but are falling, particularly in younger age groups; in the last 10 years CHD mortality has fallen by 42% among UK men and women aged 16-64.(5) More than 13 million persons in the United States live with coronary heart disease (CHD) and are at risk for acute coronary syndromes (ACS).(6) According to the American Heart Association (AHA), 785,000 Americans will have an MI in 2006, and nearly 500,000 of them will experience another. (6) In contrast to developed economies, the risk of metabolic and cardiovascular diseases (CVD) is reported to be highest in affluent urban sections of the population in third world countries (7).While age-adjusted mortality from CHD is gradually falling in developed countries (8). In developing countries, due to changing life styles and development of civilization, an increase in the incidence of MI was observed. Published data from Ministry of Health,


Iran showed that the percentage of death due to cardiovascular diseases, in particular MI, increased significantly in the recent decade and roughly it accounted for 40% of all deaths (9). Overall, Most studies show that 4% to 10% of patients with acute myocardial infarction (MI) are below 45 years of age.(10)The World Health Organization (WHO) predicts that cardiovascular diseases would be the leading cause of morbidity and mortality in the developing countries by the year 2020(11). There is high prevalence of certain risk factors in the Arabian Gulf countries. Studies indicate a high prevalence rate of type 2diabetes among adult populations (15-18%),followed by Obesity, and smoking (12).Therefore, it would sound reasonable to assume that the Arabian Gulf Region of the Middle East is at real risk of an epidemic of coronary artery disease (CAD). One form of CAD is acute coronary syndromes (ACS) (13).The overall prevalence of CAD in KSA is 5.5% (14),Oman 23.6% ,United Arab Emirates 19.9%, Qatar 5.4% , Bahrain 3.4% , Kuwait 32.0% , Yemen 15.7% .(13) Atherosclerosis is a disease of the blood vessel with deposition of lipids within the vessel wall. ACS occurs when an atherosclerotic plaque ruptures and disrupts blood flow in the coronary vessels. The diagnosis of acute coronary syndrome is extraordinarily prevalent.(15) The importance of plaque rupture and thrombosis in the pathogenesis of acute coronary syndromes is well established, presentation with myocardial infarction or unstable angina depending largely on whether the thrombus is occlusive or sub occlusive (16) . It is well known that presentation of AMI may have many variants.(17) Understanding the factors associated with atypical presentation may help in the earliest identification and treatment of these patients with MI(18) Among the symptoms shown to be associated with unrecognized AMI are dyspnea, Nonproductive cough, fatigue, abdominal or epigastric pain, nausea, vomiting, syncope, or palpitation.(19) Identifying the symptoms and signs of AMI is paramount for successful management and early treatment. Patients must realize that their symptoms may be consistent with cardiac disease and numerous reports have shown that patient may delay seeking care if they do not know that their symptoms may be consistent with MI. The problem is further compounded if patients believe that chest pain is a necessary hallmark feature of acute MI.(19) Accurate diagnosis of acute coronary syndrome should begin with careful history taking and physical examination, with particular emphasis on


categorization of a patient's level of risk. In conjunction with electrocardiographic and laboratory data, each patient with chest pain can be stratified into groups of high, intermediate, or low risk according to guidelines established by the American College of Emergency Physicians and the Agency for Health Care Policy and Research (20). Patients at high risk are admitted, while patients at intermediate risk are assigned to short-stay units where physicians can rule out acute infarction and assess for acute coronary syndrome not definitively resulting in infarction. Patients at low risk are referred for close outpatient evaluation within 72 hours (21) . It seems likely that changing lifestyles such as high consumption of processed foods rich in saturated fat and a low level of physical activity along with the rising prevalence of obesity and type 2 diabetes are leading to a progressive increase in the prevalence of cardiovascular (CVD) risk factors and CHD in developing countries (22) . Ischaemic heart disease (IHD) is the leading cause of death globally. In 2001, IHD accounted for 7·1 million deaths worldwide, 5·7 million (80%) of which were in low-income countries. Between 1990 and 2020, these diseases are expected to increase by 120% for women and 137% for men in developing countries, compared with 30–60% in developed countries. By 2010, 60% of the world’s heart disease is expected to occur in India. Furthermore, South Asians have a high prevalence of risk factors, and have IHD at an earlier age than do people in developed countries. (23) Coronary artery disease has been reported to be the leading cause of mortality in Saudi Arabia, Bahrain and the United Arab Emirates. However, there is little comparative data available about the rates of occurrence, risk factors and mortality of CAD among Arabs living in Middle Eastern countries(24). Recognition of risk factors in different groups of people may significantly affect prevention strategies and can be especially very useful in the younger ages. (25)


There is a strong need to pay attention to the rise of CAD and resulting ACS in our country. From the archives of Al-Gamhouria hospital we found that from total of ((969))Yemeni patients admitted with cardic disease,((211))patients where due to an ACS during the year 2007. In general, clinical presentation and outcome of acute myocardial infarction (AMI) and coronary artery disease vary across regions and differ from country to country. Significant differences in the prevalence of AMI exist with respect to gender, age and ethnicity, Despite major progress in prevention, diagnosis, and treatment, coronary artery disease is the leading cause of mortality in the general population(26) Strategic plans to prevent chronic vascular diseases are the keys to an effective approach to global health equity.(27)It is time we collaborate with international organization in various preventive programs and researches. Health awareness programs regarding the cause and consequences of chest pain should be conducted in our country. Early diagnosis and effective treatment is the key to reduce morbidity and mortality in our countries.

42 من 38الصفحة wwww.yemen-nic.info

Objectives General Objectives: To know the pattern of presentation of Coronary Artery Disease in patients admitted to Algamhouria modern general hospital, in the period 1st July 2008_31st December 2008. Specific: 1: To determine the frequency of Acute coronary syndrome. 2: To detect the distribution of risk factors in patients with Acute coronary syndrome. 3. To provide information on the clinical picture of patients with Acute coronary syndrome. 4. To find out the frequency of early complications among patients of Acute coronary syndrome. 5. To determine hemodynamical changes( killip classification)in patients with Acute coronary syndrome. 6. To identify the mortality rate of Acute coronary syndrome. 7.To correlate between the clinical features and prognoses in patients with Acute coronary syndrome. Collateral objectives:- 1.To fulfill the master degree requirements in internal medicine. 2.To increase the awareness about the Acute coronary syndrome risk and decrease it's mortality


Conclusion

Our study has clinical implications which concluded:- 1:-Most of our patients have STEMI(37.9%). 2:- Young patients with ACS differ from older patients in their clinical presentation, and outcome. 3:-Young patients often present with STEMI and Unstable angina. 4:-Different risk factors exist for different age groups in the Yemeni population, with smoking, khat chewing , obesity, hypercholesterolemia and a strong family history of vascular disease being common in young patients. 5:- Diabetes mellitus, hypertension and overweight being found more frequently in older patients. 6:-Significant differences in risk-factor status were also found between genders, with smoking and khat chewing and Overweight predominating in male, while hypertension, diabetes and obesity occurred most often in female. 7:-The female in our study were more likely than the male to have complication during hospitalization, and atypical presentation. 8:-we have also reported that female and older patients with ACS have higher in-hospital mortality rates than male and young patients.


RReeccoommmmeennddaattiioonn 1.There is a need for the implementation of strategies aimed at incorporating evidence into clinical practice that expand the use of proven, effective, medical therapy, focusing on elderly patients, with the aim of reducing the burden of ACS. 2.Special attention is needed to preventive measures for DM and Hypertension in females and smoking and khat chewing in males. 3.Health awareness programs regarding the cause and consequences of chest pain should be conducted in the urban as well as the rural areas. 4.The need for increase medical member knowledge for every new about IHD for early diagnosis and effective treatment to reduce morbidity and mortality The development of IHD relates strongly to lifestyle and to modifiable physiological and biochemical factors. 5.This study is a stepping stone to further hypothesis driven research.


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