Be familiar with the basics of this condition and its management.
Cardiovascular disease (CVD) is the leading cause of mortality in the United States. The risk of CVD and coronary heart disease increases proportionally with cholesterol levels. As optometrists, we often see ocular signs of hyperlipidemia, such as arcus senilus, xanthelasma, or changes in retinal blood vessels. In our roles as primary care providers, we should all be familiar with the basics of this condition and its management so that we can remain an integral part of the health care system.
Special proteins called lipoproteins combine with the blood to dissolve cholesterol. The cholesterol, which the liver secretes into the blood, is combined with one of two agents: very low-density lipoproteins (VLDL) or high-density lipoproteins (HDL). VLDL cholesterol is then metabolized in the bloodstream to produce LDL cholesterol.
LDL cholesterol: These are lipoproteins that are combinations of lipids (fats) and proteins; lipids are transported in the blood in this form. The low-density lipoproteins function to transport cholesterol from the liver to the bodily tissues. This form of cholesterol is often called the "bad" cholesterol. In general, the higher the LDL values, the greater the risk for coronary artery disease. (See table, page 26.)
HDL cholesterol: These high-density lipoproteins transport cholesterol from the tissues of the body to the liver, where it is removed from the body in the form of bile. This is the "good" cholesterol. The higher the HDL values, the lower the patient's risk of coronary artery disease.
The National Cholesterol Education Program (NCEP) recommends that anyone 20 years or older should have a fasting lipoprotein profile (FLP) once every five years. An FLP consists of Total Cholesterol (TC), LDL, HDL and triglyceride (TG) values. If values are high, monitor the patient more closely. If intervention is required, the two general recommended approaches are therapeutic lifestyle changes and pharmacologie therapy. Recommended lifestyle changes consist of modifications to a patient's diet, increased physical activity and weight reduction. These modifications should be the starting point for all patients who are diagnosed with hyperlipidemia. In general, changes are instituted for three months before pharmacological intervention. Even then, these habits should be continued with drug therapy.
The most significant change your patients will have to make is the initiation of a diet low in total fat (25% to 35% of total calories), saturated fat (
While it is unlikely lifestyle changes alone will achieve the LDL goal, it may limit the dosage of drug required, as well as the number of medications.
HMG-CoA reductase inhibitors, or statins, lower LDL by interfering with the rate-limiting step in the production of cholesterol in the liver. They also have some impact in lowering TG levels and raising HDL levels. Because these drugs are potent and well-tolerated, they have quickly become the drug class of choice in the management of hyperlipidemia. Adverse effects are minor and most commonly include gastrointestinal (GI) symptoms and muscle aches. However, a few, rare, serious side effects such as myotoxicity and hepatotoxicity have been reported.
Statins are metabolized through the cytochrome P450 enzyme system in the liver, so reactions with other agents that work in this same system are possible. They have been shown to potentate the anticoagulant effect of warfarin. These drugs should not be given to patients with active or chronic liver disease or severe renal insufficiency.
The statins are generally prescribed for nighttime dosing because cholesterol production occurs mostly at night. Many practitioners also advise patients to take them with meals to enhance absorption. Before initiating therapy with the statins, assess liver function with lab work.
Once therapy has been initiated, continued efficacy and safety checks should be repeated after any dosage changes are made. Once a patient is stabilized, lab testing should be performed every six months. If the LDL-goal level is not achieved with the maximum dosage of a statin, consider combination therapy; the most commonly used agents in this combination therapy are bileacid sequestrants or Zeita (ezetimibe, Merck).
Bile-acid sequestrants (BAS) have been utilized in the management of hyperlipidemia for more than 30 years. These agents chiefly lower LDL with little effect on HDL and a mild increase in TG. Their mechanism of action is the binding of bile acids in the intestine, which prevents their reabsorption. This action results in an increase in bile acid formation, which results in depletion of hepatic cholesterol. There are currently three drugs available in this category: colestipol, cholestyramine and Welchol (colesevelam, Sankyo).
Although there have been few serious adverse reactions to this drug class, the annoying side effects have been prominent enough to limit their use for hyperlipidemia. It has been reported that GI symptoms affect up to 30% of patients. The most common patient complaints include flatulence, constipation, diarrhea, nausea and dyspepsia and often lead to noncompliance by patients.
These drugs are often used for patients who are intolerant of the statins or who require additional LDL-lowering after successful statin therapy. Studies demonstrate that the combination of a statin and BAS can lower LDL an additional 18% over statin monotherapy.
Zeita is one of the newest LDL-lowering medications and the first of a new class of therapeutic agents, the selective cholesterol absorption inhibitors. This agent works by selectively inhibiting cholesterol absorption from the intestine. In doing so, it helps lower LDL, but has little or no effect on TG and HDL. As with any new drug on the market, the lack of long-term data to assess clinical outcomes and adverse reactions has limited its use in clinical practice.
Zeita lowers LDL by decreasing the cholesterol absorption by 54%. Even though there is a compensatory increase in cholesterol synthesis by 89%, the net result of this agent is a reduction in LDL values. However, the main problem with this drug is lack of potency. It provides a reduction in LDL levels of only 18% to 19% reduction when prescribed as monotherapy. Thus, its chief clinical role is as adjunctive therapy when additional LDL-lowering is needed.
Fibric acid derivatives
The fibric acid derivatives (or fibrates) are primarily used to lower TG levels and raise HDL. Unfortunately, they have little effect on LDL values. There are currently two fibrates available in the market: gemfibrozil and Tricor (fenofibrate, Abbott).
One problem with these agents is their variable effect on LDL, TG and HDL. They can also caused increased LDL values in some patients with low or normal LDL and high TG values.
Overall, this drug class is well tolerated, with the chief adverse reactions reported to center around GI complaints. Take care when prescribing this agent because they can potentiate the anticoagulation effect of warfarin. In general, they are contraindicated in patients with severe renal and liver disease.
The chief clinical use of fibrates is as monotherapy in patients with elevated TG and low HDL levels. They are most commonly prescribed for their TG-lowering properties in combination with other LDL-lowering agents in patients with hypertriglyceridemia and elevated LDL.
Nicotinic acid or niacin
Nicotinic acid or niacin is one of the oldest agents available for treating hyperlipidemia. This agent has a positive effect on all aspects of the lipid profile, reducing LDL and TG and increasing HDL. Niacin is available in three forms: immediate-release (IR), sustained-release (SR) and intermediate or extended-release (ER).
Its widespread use has been limited clinically due to the prevalence of adverse effects. The most bothersome of these is flushing, which is intolerable in anywhere from 10% to 50% of patients. This flushing commonly affects the upper body and is described as a warm sensation with reddening of the skin possibly combined with some mild itching and tingling. Other adverse reactions with niacin include skin irritation, myalgias and GI upset.
Soluble fibers: Soluble fibers, such as whole grain, oat bran, guar gum pectin, and fruit/vegetable fibers, have been demonstrate to have some lowering of LDL values. Current dietary recommendations are 25gm to 30gm of soluble fiber per day. Soluble fibers are believed to decrease LDL by a similar mechanism to BAS. They increase the loss of bile acid, which results in an increased synthesis of bile acids by the body and a reduction in hepatic cholesterol. Studies show dietary intake of soluble fibers can lower LDL values by 6 to 15%.
Omega-3 fatty acids: Omega3 fatty acids (eicosapentaenoic acid or EPA and docosahexaenoic acid or DHA) have demonstrated some positive TG lowering ability. Recent studies show that doses of 3 to 5gm per day of EPA or DHA can decrease TG values by 30% to 50%.
Garlic: Although commonly believed to lower cholesterol, clinical studies on the effect of garlic in this role vary. A recent meta-analysis of human trials found that garlic resulted in a minimal effect on TC (a reduction of 5.8%) with no significant effect on LDL or HDL values. One of the problems that limits the widespread use of this agent to lower cholesterol, along with poor efficacy, is the incidence of adverse effects such as GI symptoms, garlic breath and body odor.
References available on request.
by Deepak Gupta, O.D., .F.A.A.O. and Sonia Gupta, Rp.H., M.S.
with Deepak Gupta, O.D., F.A.A.O.
Dr. Gupta practices full scope optometry in Stamford, Conn. He's also clinical director of The Center for Keratoconus at Stamford Ophthalmology. K-mail him at Dcegup4919@hotmail. com.
Ms. Gupta is a clinical pharmacist who has years of both retail and hospital pharmacy experience.
Copyright Boucher Communications, Inc. Jul 2005
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