Hypercholesterolemia progression

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

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). 

B60. Buja, L. M., Kita, T., Goldstein, J. L., Watanabe, Y., and Brown, M. S., Cellular pathology of progressive atherosclerosis in the WHHL rabbit An animal model of familial hypercholesterolemia. Arteriosclerosis 3, 87-101 (1983). 

Parsons WB (1961b) Treatment of hypercholesterolemia by nicotinic acid progress report with review of studies regarding mode of action. Archives of Internal Medicine 107, 639-52. 

Napoli C, Glass CK, Witztum JL, Deutch R, D Armiento FP, Palinski W. 1999. Influence of maternal hypercholesterolemia during pregnancy on progression of early atherosclerotic lesions in childhood fate of early lesions in children (FELIC) study. Lancet 354 1234-41... 

Reductions in elevated total cholesterol and LDL cholesterol reduce coronary heast disease mortality and total mortality increasing HDL reduces coronary heart disease events as well. Aggressive treatment of hypercholesterolemia results in fewer patients progressing to myocardial infarction, angina, and stroke and reduces the need for interventions such as coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. 

Atherosclerosis progresses in a series of stages, although some lesions at each stage may not progress further or may even regress if inciting events, such as hypercholesterolemia. 

Atherosclerosis use to slow the progression of coronary atherosclerosis. Hypercholesterolemia nse for reduction of elevated total cholesterol, LDL, apo-B, and triglyceride cholesterol levels and to increase HDL levels. Secondary prevention of coronary events used to reduce the risk of undergoing coronary revascularization procedures in patients with coronary heart disease. 

All HMGRIs are approved for the treatment of primary hypercholesterolemia and familial combined hyperlipidemia (Fredrickson s type Ha and lib) (Table 30.2) In patients who have not responded to diet, exercise, and other non pharmacological methods (Table 30.6) (15,21). They may be used either alone or In combination with bile acid sequestrants, ezetimibe, or niacin. As previously mentioned, they should be administered at least 1 hour before or 4 to 6 hours after bile acid sequestrants when this combination Is desired. Fluvastatin, lovastatin, pravastatin, and simvastatin have been specifically Indicated to reduce the mortality of CHD and stroke. By reducing plasma LDL levels, these compounds slow the progression of atherosclerosis and reduce the risk of myocardial Infarction and other ramifications of vascular occlusion. Atorvastatin, rosuvastatin, and simvastatin have been shown to be effective In homozygous familial hyperlipidemia and are Indicated for this use. Additionally, atorvastatin, pravastatin, and simvastatin are Indicated for primary dysbetallpoprotelnemla (Fredrickson s type III) (Table 30.2). Finally, atorvastatin, pravastatin, rosuvastatin, and simvastatin are Indicated for the treatment of hypertriglyceridemia. 

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