The inciting cause of coronary heart disease (atherosclerosis), a disease now responsible for more deaths in the U.S. than cancer and HIV disease combined, is not known. However, the close relationship between its incidence, severity and rapidity of progression and blood cholesterol levels is unmistaken. Many scientific studies have clearly validated the so-called "lipid hypothesis", which states that the rate at which lipoproteins (cholesterol and other fatty chemicals) reach the inner lining tissues of arteries is directly related to their concentrations in the blood. Scientific studies have also convincingly proven that reducing the blood levels of these lipoproteins reduces the rate of progression of atherosclerosis.
Cholesterol is a most important chemical building block in the body's manufacture of a variety of hormones, cellular structural components and bile. As a fat it will not dissolve in the blood, which is predominantly water based, and so to be carried in the bloodstream cholesterol is bound to a variety of different proteins. Laboratories can separate these various cholesterol binding proteins by their differing densities, producing the commonly described HDL - high density lipoprotein cholesterol, and LDL - low density lipoprotein cholesterol.
HDL and LDL cholesterol particles apparently serve differing chemical purposes. HDL particles participate in the retrieval of cholesterol from the arterial wall, while cells within the arterial wall actively take up LDL-cholesterol and participate in the creation of "plaque".
The single most important component of blood cholesterol regulation is dietary modification. Aggressive restriction of both cholesterol and saturated fat intake has an enormous impact on lowering LDL levels. Reduction of total daily caloric intake, carbohydrates and proteins as well as fats further reduces the body's rate of cholesterol manufacture.
Present National Institute of Health (NIH) guidelines call for reduction of total and LDL cholesterol levels to 200mg% and 140mg% respectively. Patients with known atherosclerosis or with a profound family history of coronary heart disease (CAD) and several other CAD risk factors are further recommended to have their LDL cholesterol levels reduced to less than 100mg%.
While not as potent a CAD risk factor as elevated cholesterol, severely elevated levels of triglyceride (a different form of fat) are also known to accelerate atherosclerosis. Strict dietary controls and finely tuned regulation of diabetes mellitus, when present, are usually adequate for maintaining "safe" blood triglyceride levels, however, when these levels exceed 300-500mg%, drug therapy is indicated.
Drug Therapy
Drugs used to lower blood cholesterol levels work in either of two general ways. One group of drugs limits the amount of cholesterol manufactured by the liver (the "statins" and niacin), while another group increased the elimination of cholesterol from the body (bile acid binding resins). Fibric acid derivatives are the only class of available drugs that specifically reduce severely elevated triglyceride levels.
Today, the most frequently prescribed class of cholesterol lowering drugs, the HMG-CoA reductase inhibitors, a.k.a. “statins,” act by inhibiting an enzyme which plays an important role in cholesterol synthesis. By in large, the statins are the easiest of the cholesterol lowering drugs to use as their response rate is highly predictable and their side-effect rate is low. Occasional muscle aches or nausea are the most common reasons for stopping these drugs, but severe muscle or liver inflammation can occur and therefore these drugs must be closely monitored.
While all presently available statins are closely chemically related, the different members of this group may vary significantly in cholesterol lowering power and price. Some of the most commonly used statins include atorvastatin, lovastatin, cerivastatin, pravastatin, fluvastatin, and simvastatin.
Nicotinic acid (niacin) is one of the B-complex vitamins, which in high doses, lowers the rate of cholesterol synthesis. Additionally, niacin slows HDL-cholesterol degradation and triglyceride secretion more than the statins, thereby elevating HDL-cholesterol and reducing triglyceride levels, while also lowering LDL-cholesterol. While niacin may sound like a perfect cholesterol-lowering drug, its frequency of minor but very poorly tolerated side effects greatly limits its usefulness. Intense flushing sensations, nausea and bloating are the most common patient complaints, and starting on a very low dose and slowly titrating to a higher, effective dose can sometimes prevent these. As with statin drugs, liver function tests must be monitored. Patients with gout should probably avoid niacin.
Many non-prescription, short and long acting formulation of niacin are available, although several sustained release, prescription-only versions, purporting to be better tolerated, are also available.
Bile acids, the major components of bile that are produced in the liver, are created from cholesterol. Once secreted into the small intestine, the majority of bile acids are reabsorbed and re-utilized. Two presently available drugs bind to the bile acids within the small intestine and prevent their reabsorption (bile acid binding resins). The body must then make up for this bile acid loss by manufacturing more and thereby using up more of the bodies cholesterol supply. As these drugs are never absorbed into the body, but just remain inside the intestine, they have few systemic side effects. As with niacin, frequent abdominal bloating, cramping and diarrhea greatly limits the use of these drugs. Bile acid binding resins come as granules that must be thoroughly mixed with water or juices and are taken two to three times daily. These resins may also bind to other medications being taken and a so a carefully planned dosing regimen must be developed by the patient and physician.
Cholestyramine and colestipol are the two currently available compounds in this class of drugs.
Only one class of drugs is currently available that specifically lowers severely elevated blood triglyceride levels, fibric acid derivatives. These drugs increase the metabolic breakdown of triglyceride containing lipoproteins (VLDL particles). Although generally very well tolerated, some patients may develop abdominal discomfort and gallstone disease may be aggravated.
The most commonly used fibric acid derivatives presently prescribed are gemfibrizol and fenofibrate. Clofibrate, while still available, is used much less due to its known association with gallstone formation.
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