Hyperlipidemia is the leading risk factor for atherosclerosis. The American Heart Association (AHA) estimates that 99.5 million American adults have total blood cholesterol values of 200 mg/dL or higher. Of these Americans, 39.9 million have levels above 240 mg/dL, which is considered high. Levels of 200-239 mg/dL are borderline-high. Differences exist between men and women in various age groups in relationship to the components of cholesterol levels. There are further differences between various ethnic groups.1
Cholesterol and triglycerides are plasma lipids carried in the blood. Cholesterol is a steroid obtained exogenously from one's diet and is naturally synthesized endogenously by the liver. Triglycerides consist of three fatty acids connected to a glycerol molecule.
There are two categories of triglycerides based on the level of saturation with hydrogen. Saturated fatty acids are unable to absorb more hydrogen and are solid at room temperature, whereas unsaturated fatty acids are able to absorb more hydrogen and are liquid at room temperature.
Lipoprotein complexes carry cholesterol and triglycerides in circulation. Low-density lipoproteins (LDLs) carry 60-70 percent of total serum cholesterol. High-density lipoproteins (HDLs) are 25 percent phospholipid, 20 percent cholesterol, 50 percent protein and 5 percent triglycerides. Research indicates that HDLs take cholesterol to the liver for clearance.
Children and premenopausal women have higher levels of HDLs. Weight loss, stress reduction, exercise and cigarette-smoking cessation increase levels of HDLs. Smoking increases levels of LDLs and reduces levels of HDLs.2
Atherosclerosis is a process initiated by interruption of endothelial function that is precipitated by behavioral, physiological and genetic factors. It can be defined as a variable combination of changes in the intimal layer of the arteries consisting of an accumulation of lipids, complex carbohydrates, blood and its products, fibrous tissue and calcified deposits. These changes may extend into the medial layer.
The National Institutes of Health's (NIH) National Heart, Lung and Blood Institute has recommended the following nine-step approach to hyperlipidemia management.3
1. Determine lipoprotein levels after 9-12 hour fast. The primary target is LDL cholesterol.
2. Identify the presence of clinical atherosclerotic disease that confers high risk for coronary artery disease.
3. Determine the presence of any major risk factors other than LDL.
4. If two or more risk factors other than LDL are present, assess 10-year coronary artery disease risk according to Framingham tables.
5. Determine risk category and establish the goal of therapy.
6. Initiate therapeutic lifestyle changes via diet, weight management and increased physical activity.
7. Consider adding drug therapy.
8. Identify and treat any metabolic syndrome.
9. Treat elevated triglycerides.
Pharmacological interventions in this nine-step approach are addressed here. It is important to note that the evaluation process, diet, weight management and increased physical activity steps of these recommendations are considered the primary components before initiating drug therapy.1,3
Drugs Affecting Lipid Metabolism
There are basically four classes of drugs that affect lipid metabolism: HMG CoA reductase inhibitors (statins), bile acid sequestrants, nicotinic acid and fibric acids.4
HMG CoA Reductase Inhibitors - The HMG CoA reductase inhibitors, or statins, exert their influence by targeting the rate-limiting enzyme for cholesterol synthesis (HMG CoA reductase). This effectively increases plasma clearance of LDL and decreases hepatic production of LDL. Patients placed on this drug category must be screened for active or chronic liver disease. Intermittent assessment of liver function is necessary during therapy.
The statins as a class of drugs are well-tolerated and their safety profiles are similar. The major side effect of statins is myopathy, which is described as muscle pain or weakness associated with creatine kinase levels higher than 10 times the normal limit. Symptoms may include fever and malaise. Rhabdomyolysis and acute renal failure may result if myopathy is not recognized. Discontinuation of the drug is necessary.
Currently approved drugs in this classification with their dose range are shown in Table 1.
|Table 1: Currently Approved Statin Drugs & Their Dose Range7
Some drugs interfere with the metabolism of statins and can increase plasma levels. These agents include certain antibiotics, antifungal medications, antiviral drugs, grapefruit juice, amiodarone and antihypertensive agents.
The HMG CoA reductase inhibitors have been associated with some other potentially important effects on the vascular system. Hypercholesterolemia reduces endothelial production and increases degradation of nitric oxide. Cholesterol reduction with statins results in improvement in endothelial function.5 The Scandinavian Simvastin Survival Study6 demonstrated a significant reduction in mortality among the subjects in the treatment group versus the placebo group. The Cholesterol and Recurrent Events (CARE) study looked at individuals with average cholesterol.6 Analysis revealed no reduction in coronary events among those with LDLs below 125 mg/dL.
But diabetics treated with pravastatin had a 25 percent reduction in major coronary events compared to diabetics taking placebo. Statins may affect thrombus formation, erythrocyte deformability and levels of plasminogen activator inhibitor-1 and fibrinogen. Further research is needed in this area.
The CARE trial sub-analysis showed that pravastatin lowered the levels of C-reactive protein and eliminated the risk of cardiovascular events associated with that inflammatory marker.6
Rorenson and Tangney have suggested that there may be four non-lipid mechanisms that result in the benefits that are seen in clinical events.6 These mechanisms include modification of:
plaque stability; and
These mechanisms are not equal for all statins.6
Bile Acid Sequestrants - The bile acid sequestrants or bile acid-binding resins act to interrupt the enterohepatic circulation of bile acids by inhibiting reabsorption in the intestine. These resins are not absorbed systemically but remain in the intestine and are eliminated.
This class of drugs is used as an adjunct for severe hypercholesterolemia. They may be used in combination with statins. The side effects of this class of drugs are primarily gastrointestinal (GI) - constipation, fullness and GI discomfort. Drugs approved in this classification and their dose ranges are shown in Table 2.
|Table 2: Approved Bile Acid Sequestrant Drugs & Dose Ranges2
Nicotinic Acid - Nicotinic acid (niacin) is now available in immediate-release, extended-release and sustained-release formulas, which may help patient tolerance of these drugs, also referred to as fibrates. The exact mechanism of action is unknown but may be decreased esterification of triglycerides in the liver.
Use of niacin is effective in increasing HDL and lowering triglycerides. It has modest effect on LDL. In the Coronary Drug Project, niacin decreased mortality at 15 years.7 Absolute contraindications to niacin use are chronic liver disease and severe gout. Relative contraindications include diabetes, hyperuricemia and peptic ulcer disease. Side effects include flushing, hyperuricemia, hepatotoxicity, hyperglycemia and gastritis.7
Fibric Acid Agents - The fibric acid agents are indicated when diet and lifestyle changes are insufficient to treat hypertriglyceridemia. The drugs are also indicated in prevention of cardiovascular disease in patients with elevated triglycerides and low HDL.
Absolute contraindications to this class of drugs are severe renal disease and severe hepatic disease. Side effects include dyspepsia, gallstones and myopathy. Drugs approved by the FDA in this class are shown in Table 3.
|Table 3: Approved Fibric Acid Drugs & Dose Ranges8
||600 mg |
Nurse's Role in Lipid Management
Nurses need to take responsibility for getting patients involved in their lipid management program. Part of the program involves the assumption of responsibility by the patient for lifestyle modification. The recommendation from NIH is to start dietary therapy in all patients with a goal of less than 7 percent of total calories from saturated fats in order to maintain cholesterol under 200 mg/dL and encourage consumption of omega-3 fatty acids.
The second part of the program includes a consistent physical activity program that is planned in relationship to the patient's age and physical condition.
Pharmacological intervention in lipid management has two goals. The primary goal is to maintain LDL under 100 mg/dL. If the LDL is below this level, LDL-lowering therapy is not required. If the patient has a low HDL or high triglycerides, one might consider the fibric acid agents or niacin to manage those elements.
If the patient has a baseline LDL of 100-129 mg/dL, there are several options, depending on the rest of the lipid profile. One option is to intensify the lipid-lowering therapy with a statin. A fibrate or niacin may be added if the HDL is low or the triglycerides are high. In some cases it may be necessary to consider combined drug therapy.
The secondary goal is to keep triglycerides below 200 mg/dL. If the triglycerides are > 150 mg/dL or HDL is <40 mg/dL, the emphasis should be placed on weight management and physical activity. If triglycerides are between 200 and 499 mg/dL, one should consider starting the patient on a fibrate or niacin after a course of lipid-lowering therapy.
If the triglycerides are > 500 mg/dL fibrates or niacin should be started before lipid-lowering agents. In these cases omega-3 fatty acids may be considered as an adjunct for high triglycerides.3
Patient Education Important
Education of the patient related to diet and exercise is important when lipid-lowering pharmacological intervention starts. The need for routine monitoring of liver and kidney functions must be stressed. Patients on statins should understand that certain drugs and foods interfere with the metabolism of the statins and will increase plasma levels. Those drugs include frequently prescribed cardiovascular drugs for hypertension, heart rhythm disturbances or other disorders.
Each patient visit should include a complete review of the patient's medication profile by the physician or nurse practitioner. Discharge medications must be thoroughly reviewed with the patient and family to assure compliance with treatment goals and improve patient outcomes.
The AHA's "Get With the Guidelines" program and the JCAHO ORYX Core Measurement Set9 include lipid management as part of the assessment of care for the acute myocardial infarction patient. Both of these programs are quality improvement initiatives that consider evidence-based medicine in the development of a core set of patient indicators that have been established to improve cardiac patient outcomes.
Patient and family involvement in medical management can improve the quality of patient outcomes. Lipid-lowering agents are an integral part of that management, and patient education about those drugs may increase their effectiveness.
Patricia Jamison Reilly is regional clinical coordinator for the western region of Genentech Inc., headquartered in South San Francisco, CA.