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New Treatments for Hyperlipidemia

Atherosclerosis can result in disabling myocardial infarction, stroke, or even sudden death. Recent clinical data firmly substantiates that each of these endpoints is preventable through risk factor modification and cholesterol reduction. Reducing cholesterol results in stabilization of the atherosclerotic plaque, reduces its vulnerability to rupture, and reduces its thrombogenicity. These measures also improve endothelial function thereby restoring its normal vasodilator function.

Eleven million Americans today have atherosclerosis, manifesting clinically as coronary artery disease. Treatment of lipoprotein abnormalities that fat, cholesterol, low fat contribute to atherosclerosis and whose treatment has been substantiated to reduce morbidity and mortality from coronary artery disease, are often ignored.

Pathogenesis of Acute Coronary Syndromes

Pathogenesis of Atherosclerosis: Plaque stability and clinical events. The life history of atherosclerotic plaque is not one of continuous linear growth and lumenal narrowing, but cyclic periods of growth associated with inflammatory activation. Stable angina is associated with a plaque that has structural integrity but in which inflammatory activity is low or absent and results from the loss of a patent lumen movement as well as loss of endothelial dependent dilation mechanisms. During periods of heightened inflammatory activity, inflammatory cells and prothrombotic mediators and vasoconstrictor substances are recruited which may be the nidus for plaque fracture and rupture resulting clinically in an unstable coronary syndrome or myocardial infarction. Thus the therapeutic objectives for atherosclerosis perhaps should be directed at reducing the factors which lead to activation of coronary lesions. It may be that the biological activity of a lesion is a more important determinant of its clinical course that is the extent of stenosis. This paradigm suggests that the treatment of atherosclerosis should be directed at modification of known risk factors such as smoking in patients with clinical evidence of vascular disease at any stage of life or disease progression.

Can Coronary Disease be Reversed?

Regression trials

Studies using arteriography to determine change in coronary obstruction have indicated progression, stabilization, or regression of coronary lesions associated with changes in plasma lipids and lipoproteins. Non-pharmacological treatments increased the chance of regression of atherosclerosis compared with controls by 15-40% and decreased the chance of progression by 25-35%. Among' pharmacological and one surgical trial, the chance of lesion regression compared to controls increased 34% and that of lesion progression decreased by 35%. In general these changes were associated with favorable changes in lipid profiles which in non-pharmacological trials included a decrease in total cholesterol of 14%, a decrease in LDL of 17%, and in increase of HDL.