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For Patient - Heart Coronary Artery Disease |
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Coronary Artery Disease |
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Coronary artery disease (CAD) has become a global epidemic, responsible for almost 30% deaths worldwide. Cardiovascular diseases were responsible for nearly 16.7 million fatalities globally in 2002, with majority in the developing countries.
In the developed countries, there has been an encouraging decrease in mortality due to CAD, with a persistent rise in the developing countries like China and Eastern European countries. Similarly, there has been a six-times increase in the incidence of CAD in the Indian urban population. Collectively all such developing countries account for more than 70% of the world population.
The variations in culture, ethnicity, race, socioeconomic status and lifestyle are responsible for differences in the prevalence and incidence of CAD. Many studies have demonstrated a higher incidence of cardiovascular morbidity in non-Caucasians, compared with Caucasians. The classical risk factors, such as higher amount of saturated fats in diets, elevated serum cholesterol; hypertension and diabetes are the main attributes for CAD in the Western Europeans. Whereas, in East European countries, a higher incidence of smoking, excessive alcohol intake along with diets rich in saturated fat and shoddier social conditions play a major contributory role. In the rapid developing economies like China, it is further compounded by sedentary life styles, rapid industrialization, urbanization, and increased stress in daily life. In the Indian population, higher levels of Lipoprotein (a) and insulin resistance play additional crucial roles in disease development. A family history of heart disease is associated with 2-7 times higher risk of CAD. The control of modifiable risk factors is the best option to prevent premature CAD, regardless of cultural, social, ethnic and economic variations.
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Pathogenesis of Coronary Atherosclerosis |
Coronary artery disease depicts presence of coronary atherosclerosis. Atherosclerosis initiates during adolescence and increases throughout life with progressive narrowing of the vessel lumen and impaired myocardial blood flow. The process of atherosclerosis can be considered as “a healing attempt of endothelial injury, caused by the risk factors”. Lipid and cholesterol metabolism is the primary known genetic factor in atherosclerosis, with already more than 150 types of mutation discovered. A multitude of complex factors, such as CD-40L signaling, Chlamydia antigens, oxidized LDL, macrophage apoptosis and macrophage-lymphocyte interactions contribute in the process of atherogenesis. There are also inter-relationships between endothelial injury, and risk factors, such as family history, smoking, diabetes mellitus, hypertension, obesity hyperlipidaemia, and a sedentary lifestyle. In older age, the endothelial dysfunction becomes more pronounced; causing reduced arterial compliance and increased vessel stiffness representing “Vascular Aging”. This leads to a higher incidence of hypertension and atherosclerotic disease.
Atherosclerotic plaques characteristically occur in vascular regions where blood undergoes sudden changes in velocity and direction of flow, causing shear stress on the endothelial surface. Such segments are mostly present at the bifurcations, origin of smaller branches and areas of marked curvature and geometric irregularities. The development of fatty streaks between the endothelium and the internal elastic lamina secondary to oxidation of LDLs is the first critical step in the initiation and pathogenesis of e atherosclerotic lesions. Over time, an extra cellular lipid core, layers of smooth muscle and a connective tissue matrix with a fibrous cap constitutes an intermediate lesion. Endothelium secretes various chemicals to preserve the vascular tone. The risk factors speed up endothelial dysfunction and vascular inflammation, causing impaired endothelium-dependent dilation and paradoxical vasoconstriction. Endothelial dysfunction leads to inactivation of nitric oxide by the excess production of free radicals and reduced transcription of nitric oxide synthase messenger RNA (mRNA). Reduced nitric oxide results in increased platelet adhesion, increased plasminogen activator inhibitor, decreased plasminogen activator and increased tissue factor, enhancing platelet thrombus formation. Simultaneously, oxidized LDL activates inflammatory processes at the level of gene transcription, with recruitment of monocytes / macrophages. The circulating monocytes infiltrate the intima of the vessel wall, and these tissue macrophages act as scavenger cells, taking up LDL cholesterol and forming the characteristic “foam cell”, which is a hallmark of early atherosclerosis. These activated macrophages also release additional factors aggravating endothelial dysfunction. The soft atherosclerotic plaques may either organize over time with a fibrous cap and some calcification or may rupture, exposing the underlying thrombogenic core of lipid and necrotic material to circulating blood, resulting in platelet adhesion, aggregation, and progressive luminal narrowing, responsible for Acute Coronary Syndromes.
There is an increasing body of evidence suggesting that atherosclerotic progression could be result of micro inflammation mediated by pro-inflammatory cytokines. A relationship between total infectious burden and extent of atherosclerosis has been proposed, whereby multiple infectious pathogens may act synergistically to cause vascular damage. Biochemical markers such as elevated levels of C-reactive protein and interleukin-6 signal more rapidly advancing coronary artery disease and unstable plaques, requiring aggressive preventive measures. The statins lower circulating levels of C-reactive protein, either due to an anti-inflammatory effect or secondary to their effect on hepatic lipid homeostasis. Therefore,multitude and complexity of pathogenesis of CAD calls for individualization of treatment decisions for each patient, considering clinical symptoms, risk factors, the type and location of the lesions involving coronary arteries, extent and severity of ischaemia, cardiac function and prognosis.
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| 1. S Mahmood, Functional Imaging of Coronary Artery and Congenital Heart Diseases in Clinical Nuclear Medicine (III rd edt; 2006) by Hodderr Publishing, London, UK |
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