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Chapter: Modern Pharmacology with Clinical Applications: Hypocholesterolemic Drugs and Coronary Heart Disease

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When to Treat Hypercholesterolemias?

Principal risk factors for heart disease are elevated lev-els of LDL cholesterol, a family history of heart disease, and hypertension.

WHEN TO TREAT HYPERCHOLESTEROLEMIAS?

Principal risk factors for heart disease are elevated lev-els of LDL cholesterol, a family history of heart disease, and hypertension. Other risks include being male, smoking, low levels of high density lipoprotein (HDL) cholesterol, diabetes mellitus, hyperhomocystinemia, high levels of lipoprotein a (Lpa), and high blood levels of C-reactive protein. (Table 23.1). C-Reactive protein is a marker for cellular inflammation.


Homocysteine blood levels (>15 mol/L) promote atherosclerosis, perhaps by stimulating proliferation of arterial wall smooth muscle cells. Supplementing the diet with folic acid can reduce high levels. Lpa is a mod-ified LDL particle that is both atherogenic and pro-thrombic.

Although development and clinical expression of coronary heart disease (CHD) are determined by the interaction of numerous risk factors, lowering blood cholesterol is the major approach to prevention and suppression of heart disease, the number one cause of death in Western society. The risk of CHD is directly proportional to blood cholesterol levels (Fig. 23.1), and a lowering of cholesterol, specifically LDL cholesterol, deceases the incidence of heart attacks.


The results of several large clinical trials using the statin drugs (discussed later) show that the tested drugs decreased the risk of both primary and secondary car-diovascular events. The incidence of myocardial infarc-tion and death from cardiovascular disease was reduced in patients with hypercholesterolemia who never had a heart attack (primary prevention) and in those with heart disease (secondary prevention). Furthermore, the statins decreased the risk of a first heart attack in sub-jects with even average LDL cholesterol levels. In addi-tion to decreased clinical expression of heart disease, aggressive lowering of blood cholesterol with the statin drugs can partially reverse atherosclerosis in the sense of reducing the degree of stenosis (closure) of coronary arteries. Guidelines for initiation and goals of treatment of hypercholesterolemias are outlined in Table 23.1.

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