Clinical Manifestations of Atherosclerosis

Only nine years after its discovery in plasma as an antigenic trait, a relationship was suggested between lipoprotein(a) and coronary heart disease (CHD) (B6, D2). Moreover, an interesting relationship between longevity and Lp(a) concentrations was reported by Berg (B10) The frequency of higher Lp(a) levels in very old persons ( 83 years) was lower than in the reference population. The same observation was made by Knapp (K18) in black American men. This 

The association between Lp(a) levels and CHD was confirmed in the early 1970s and 1980s by a large number of retrospective case-control studies (A3, A14, B8, B9, F15, K21, W4). These studies could only establish a qualitative association, but recently this association was confirmed both retrospectively and, to a lesser extent, also prospectively (B3, D4, G13, G15, G21, L3, PI, S6, S19, VI). Some investigators, however, could not confirm this association (J2, R8). 

Dahlen et al. showed in their prospective analysis that Lp(a) is an independent risk factor for the clinical manifestations of coronary atherosclerosis, with a relative risk ranging from 1.6 to 3.6 (D4, D6). 

Interestingly, a threshold for CHD risk became apparent at Lp(a) levels in the range between 0.3 and 0.4 g/liter. The predictive value of Lp(a) levels proved to be comparable in magnitude to other established risk factors. 

The fact that these observations were not restricted to a Caucasian population became apparent when it was shown that similar data could be generated for Hawaiian men of Japanese ancestry (R7). Studies in Japan itself and in Chinese patients corroborated these findings and showed the generalizability of the association (S4, S7, W19). Results from the latter study indicated that Lp(a) concentrations were significantly higher in the patients with CHD than in the general population. 

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Atherosclerosis is a progressive vascular fibroproliferative-inflammatory disease. It is triggered, maintained, and driven by risk factors such as hypercholesterolemia, hyperlipidemia, and hypertonus [28]. The characteristic clinical manifestation of atherosclerosis is the atherosclerotic lesion, developing in the vessel wall (atherosclerotic plaque). 

O Ischemic heart disease results from an imbalance between myocardial oxygen demand and oxygen supply that is most often due to coronary atherosclerosis. Common clinical manifestations of ischemic heart disease include chronic stable angina and the acute coronary syndromes of unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. 

A high serum Lp(a) concentration was also reported to be a significant risk factor for all strokes in a case-control study in Chinese patients (W20). In conjunction with the associations found between Lp(a) levels and coronary atherosclerosis in different ethnic groups, the latter study and earlier reports strongly support a universal role for Lp(a) in the development and clinical manifestations of atherosclerotic disease in general (M29, W20). 

The clinical manifestations of PAD are associated with reduction in functional capacity and quality of life, but because of the systemic nature of the atherosclerotic process there is a strong association with coronary and carotid artery disease. Consequently, patients with PAD have an increased risk of cardiovascular and cerebrovascular ischemic events [myocardial infarction (Ml), ischemic stroke, and death] compared to the general population (4,5). In addition, these cardiovascular ischemic events are more frequent than ischemic limb events in any lower extremity PAD cohort, whether individuals present without symptoms or with atypical leg pain, classic claudication, or critical limb ischemia (6). Therefore, aggressive treatment of known risk factors for progression of atherosclerosis is warranted. In addition to tobacco cessation, encouragement of daily exercise and use of a low cholesterol, low salt diet, PAD patients should be offered therapies to reduce lipid levels, control blood pressure, control blood glucose in patients with diabetes mellitus, and offer other effective antiatherosclerotic strategies. A recent position paper... 

It is important to note that an elevated and/or altered plasma lipid level is only one of a wide range of risk factors that contribute to the clinical manifestations of cardiovascular disease in humans (Lusis, 2000). Consequently, in some studies, the reduced incidence of atherosclerosis in animals fed CLA was not accompanied by an improvement in the plasma lipid profile during the CLA feeding phase (Wilson et al, 2000). Reasons for these effects are not understood fully. However, atherosclerosis can also be considered as a chronic inflammatory disease (Libby, 2002) and several important anti-inflammatory effects have been associated with the use of RA these include a reduction in the expression of COX-2, PGE2, reduced release of nitric oxide, a decreased production of pro-inflammatory cytokines, and PPARy activation (Urquhart et al, 2002 Yu et al, 2002 Toomey et al, 2003). 

Aberrant thrombus formation and deposition on blood vessel walls imderlies the pathogenesis of acute cardiovascular disease states which remain the principal cause of morbidity and mortality in the industrialized world [1,2,3]. Plasma proteins, proteases and specific cellular receptors that participate in hemostasis have emerged as important risk considerations in thrombosis and thromboembolic disorders. The clinical manifestations of the above disease states include acute coronary artery and cerebrovascular syndromes, peripheral arterial occlusion, deep vein thrombosis and pulmonary/renal embolism [3]. The most dilabilitating acute events precipitated by these disorders are myocardial infarction and stroke. In addition, the interplay between hemostatic factors and hypertension (4) or atherosclerosis (5) dramatically enhances the manifestation of these pathologic states. 

Thus, inflammatory factors play a role at all stages of atherosclerosis in its initiation, progression, and final clinical manifestations. This new understanding of the pathophysiology of atherosclerosis has partly resulted from the study of chemokines and their receptors (4). 

Endothelial dysfunction is a critical event in the pathogenesis of atherosclerosis and its clinical manifestations [Mano et al., 1996 Cayatte et al., 1994], It accelerates the development of atherosclerosis and may be one of the earliest... 

This disorder has a late onset it rarely manifests itself in childhood. The most distinctive clinical presentation of dysiipoproteinemia is the presence of palmar xanthomas, the yellow deposits that occur in the creases of the palms. Tuberous and tuberoeruptive xanthomas also occur but are not unique to this syndrome. Premature atherosclerosis develops in 30% to more than 50% of these patients, particularly in the lower extremities. ... 

A clinically relevant phenomenon is described in Chapter 5. Coronary microembolization which is a frequent event in ischemic heart disease due to plaque ruptures may compromise the microcirculation with subsequent events such as arrhythmias, cardiac dysfunction, infarcts and reduced coronary reserve. Furthermore, microembolization of coronary vasa vasorum may contribute to plaque instability and propagation of atherosclerosis into the more distal coronary vascular tree. Microembolization may offer an interpretation for some unexplained manifestations of ischemic heart disease in clinical practice. 

Cardiovascular disease (CVD) remains the most important cause of morbidity and mortality in people with diabetes [1], This high-risk population is more likely to suffer a fatal event as the first manifestation of myocardial infarction (MI) or stroke, making primary prevention a priority. The pathogenesis of atherosclerosis-related disease is multifactorial but dyslipidaemia is a common and important risk predictor and is open to therapeutic intervention. Pharmacological intervention is supported by major randomised, controlled clinical trials (RCTs) of primary and secondary CVD prevention. RCTs with statin drugs have demonstrated unequivocal benefit in reducing major coronary events and stroke. 

All serum Tipids, which consist of free cholesterol, glycerides, cholesterol ester and phospholipids, circulate in association with specific proteins (apo-lipoproteins) to form lipid-protein complexes. These macromolecular complexes are called "lipoproteins" and have remarkable hydrophilic properties, in spite of high lipid contents. Therefore, water insoluble lipids are transported from their organs for synthesis to their sites for utilization. Most serum lipoproteins have a molecular weight range from approximately 200,000 to 10,000,000 and contain from 40 % to 95 % of lipids. Studies of the factors affecting lipoprotein levels are very important for health and diseases, because lipoprotein levels are closely related to atherosclerosis and its clinical manifestations. 

When cadmium exposure continues past the onset of early kidney damage (manifested as proteinuria), chronic nephrotoxicity may occur (Meridian Research, Inc. 1989 Roth Associates, Inc. 1989). Uremia, which is the loss of the glomerulus ability to adequately filter blood, may result. This condition leads to severe disturbance of electrolyte concentrations, which may result in various clinical complications including atherosclerosis, hypertension, pericarditis, anemia, hemorrhagic tendencies, deficient cellular immunity, bone changes, and other problems. Progression of the disease may require dialysis or a kidney transplant. 

Niacin is a water-soluble vitamin that has been available as a lipid-lowering medication and in prevention of atherosclerosis for half a century (Ganji et al. 2003 Olsson 2010). Numerous studies have documented its beneficial effects on reducing cardiovascular disease (CVD) (Olsson 2010). Clinically, the most well-known effect of niacin deficiency is pellagra which, as noted above, is manifested by dermatitis, diarrhoea and dementia (Bodor and Offermanns 2008 Ganji, et al. 2003). In this chapter we look at the effects of niacin on human physiology and its consequent effects on disease states. 

Bamethane sulfate (V), a dilator drug known for many years, was recently employed in two studies involving patients with obliterative atherosclerosis and intermittent claudica-tion30/31. There was distinct clinical improvement in 7 patients. One patient, who failed to show improvement in lower limb circulation, nevertheless had some relief from the manifestations of concomitant cerebral arterial disease O. 

Tools to improve cardiovascular health are of great importance in countries where life expectancy is significantly increasing and where the prevalence of lifestyle-related diseases such as cardiovascular disease and type II diabetes is constantly growing. Atherosclerosis is still the leading cause of mortality and morbidity in affluent societies. By changing diet and lifestyle the risk factors for cardiovascular mortality and morbidity can be lowered. Among these risk factors, the importance of total cholesterol and low-density lipoprotein (LDL) cholesterol levels in blood semm is well established. An elevated serum concentration of cholesterol and especially of LDL cholesterol is a key risk factor for the development of atherosclerosis and its clinical manifestations, which include coronary heart disease and cerebrovascular and peripheral artery diseases. 

Atherosclerosis is a condition of the organism characterized by elevated levels of atherogenic lipoproteins in blood plasma, lipid deposits (including cholesterol) in the form of esters inside walls of the arterial system, and it is expressed by a gradual difficulty of blood circulation. The most appropriate name for this disease is lipoproteinemia. Clinically, it is manifested in the form of ischemic heart disease, stroke, abnormal cerebral blood flow, and peripheral ischemia. 

Noninvasive detection of vascular abnormalities is of the utmost importance in clinical imaging. Indeed, a lot of injuries and diseases manifest themselves through modifications of the vasculature [1,2]. For example, abnormal angiogenesis (blood vessel growth) is observed in the development of most tumors. Embolism and atherosclerosis also manifest themselves through alterations of the blood vessels, namely through occlusions. Hemorrhage could also be detected noninvasively, which is crucial in injuries or in diseases such as ulcers [1]. 

Although CHD is manifested clinically in the fourth decade of life, evidence clearly indicates that atherosclerosis, its major cause, is a process that begins early in life and progresses silently for decades. Autopsies performed on young American soldiers killed in action in Korea and Vietnam revealed atherosclerotic lesions. Coronary artery lesions were... 

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