Lipoproteins

Apolipoproteins

Apolipoproteins are within the lipoprotein shell and contain apolipoprotein (apo) A-1, apoB, and apoE. The major component of apoA1 is HDL. The major component of apoB is LDL, which exists in two forms, apoB-100 and apoB-48. ApoB-100 has VLDL as well as LDL and is a better indicator of risk for coronary artery disease (CAD) than LDL alone.

Nonpharmacologic Methods for Cholesterol Reduction

Before drugs to lower LDL and raise HDL are prescribed, nondrug therapy should be initiated for decreasing cholesterol. Saturated fats and cholesterol in the diet should be reduced. Total fat intake should be 30% or less of caloric intake, and cholesterol intake should be 300 mg/d or less. The patient should be advised to read labels on containers and buy appropriate foods. Patients should choose lean meats, especially chicken and fish.

In many cases, diet alone will not lower blood lipid levels. Because 75% to 85% of serum cholesterol is endogenously (internally) derived, dietary modification alone will typically lower total cholesterol levels by only 10% to 30%. This and the fact that adherence to dietary restrictions is often short-lived explains why many patients do not respond to diet modification alone.

Exercise is an important aspect of the nonpharmacologic method to reduce cholesterol and increase HDL. For the older adult, exercise can be walking and bicycling. Smoking is another risk factor that should be eliminated. Smoking increases LDL cholesterol and decreases HDL.

Antihyperlipidemics

Drugs that lower lipid levels include bile-acid sequestrants, fibrates (fibric acid), nicotinic acid, cholesterol absorption inhibitor, and hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). The statins have fewer adverse effects and are well tolerated.

One of the first antihyperlipidemics, cholestyramine (Questran), is a bile-acid sequestrant that reduces LDL cholesterol (LDL-C) levels by binding with bile acids in the intestine. It is effective against hyperlipidemia type II. This group may be used as an adjunct to the statins. The drug comes in a gritty powder, which is mixed thoroughly in water or juice. Colestipol (Colestid) is another resin antihyperlipidemic similar to cholestyramine. Both are effective in lowering cholesterol. Colesevelam HCl, another bile acid sequestrant similar to cholestyramine and colestipol, is an agent that has fewer side effects (less constipation, flatulence, and cramping). Colesevelam also has less effect on the absorption of fat-soluble vitamins than the older agents and is usually the first-choice bile-acid sequestrant drug.

Gemfibrozil (Lopid) is a fibric acid derivative that is more effective at reducing triglyceride and VLDL levels than reducing LDL. It is used primarily to reduce hyperlipidemia type IV, but it can also be used for type II hyperlipidemia. This drug is highly protein-bound and should not be taken with anticoagulants, because they compete for protein sites. The anticoagulant dose should be reduced during antihyperlipidemic therapy, and the international normalized ratio (INR) should be closely monitored. Fenofibrate has similar actions and some of the same side effects as gemfibrozil. If taken with warfarin, bleeding might occur. It is highly protein-bound.

Nicotinic acid, or niacin (vitamin B₃), reduces VLDL and LDL. Nicotinic acid is actually very effective at lowering cholesterol levels, and its effect on the lipid profile is highly desirable. Because it has numerous side effects and large doses are required, as few as 20% of patients can initially tolerate niacin. However, with proper counseling, careful drug titration, and concomitant use of aspirin, this number can be increased to as high as 60% to 70%.

Ezetimibe (Zetia) is a cholesterol absorption inhibitor that acts on the cells in the small intestine to inhibit cholesterol absorption. It decreases cholesterol from dietary absorption, reducing serum cholesterol, LDL, triglycerides, and apoB levels. Ezetimibe causes only a small increase in HDL. It must be combined with a statin for optimum effect (ezetimibe and simvastatin [Zocor], marketed as Vytorin).