Hperlipidemia:- Treatment and Management Presented by:- Dr. Tewari

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Hyperlipidemia is a risk factor for accelerated vascular disease. It is a major modifiable risk factor for coronary artery disease, cerebrovascular disease, and peripheral vascular disease. The most aggressive treatment of elevated lipids should be reserved for those patients at highest risk for vascular disease: Patients with a documented history of coronary artery disease, cerebrovascular disease, or peripheral vascular disease. Patients with a history of diabetes or hypertension. Patients with an LDL-C level above 160 mg/dL. Patients with elevated triglycerides, low levels of HDL cholesterol, and those who smoke.

Screening recommendations for the general population are:  Every 5 years for males age  Every 5 years for females age Screening for adults under age 35 and over age 65 should generally be limited to those with risk factors for vascular disease which include:  Family history of premature vascular disease<50 male, <60 female)  Smoking  Hypertension  Diabetes  Documented vascular disease

Elevated cholesterol levels are generally classified as:  Desirable: TC 35 mg/dL, LDL<130  Borderline: TC , HDL>35 mg/dL, LDL , and fewer than 2 risk factors and without vascular disease  High: presence of vascular disease and LDL>160 or TC>240 mg/dL or HDL <35 mg/dL, or 2 or more risk factors.  An additional factor to consider is the total cholesterol/HDL ratio. The goal is to keep the ratio below 5:1; the optimum ratio is 3.5:1.

Treatment Step 1: Provide information on dietary modification, physical activity, and risk factor reduction. Diet should generally consist of =<30% fat, <8-10% saturated fat, <300 mg/d cholesterol. Step 2: Provide information on dietary modification, physical activity, and risk factor reduction. Diet should generally consist of =<30% fat, <7% saturated fat, <200 mg/d cholesterol.

Patients who fail maximal diet therapy may be candidates for drug therapy Risk Category Without CHD and with fewer than two risk factors Goal LDL < 160 mg/dL Without CHD and with two or more risk factors< 130 mg/dL With CHD <_100 mg/dL

TABLE 1 Determining Patient-Specific LDL Goals Through Risk Factors Risk-factor score* † Age: men > 45 years; women >55 years or postmenopausal without ERT Current smoker Hypertension Diabetes CHD in first-degree relative (male relative <55 years; female relative <65 years) HDL <35 mg per dL (0.9 mmol per L); subtract 1 risk factor if HDL >60 mg per dL

LDL goal, by risk-factor score† 0 to 1 point: <160 mg per dL (<4.15 mmol per L) 2 or more points: <130 mg per dL (<3.35 mmol per L) Patients with history of CHD: <100 mg per dL (<2.60 mmol per L)

Medication Selection  The drugs of first choice for elevated LDL cholesterol are the bile acid sequestrants (cholestyramine, colestipol) and nicotinic acid (niacin). These medications are effective and have no serious side effects. They can have troublesome side effects requiring member education to improve compliance. Niacin is preferred in the presence of elevated triglycerides (exceeding 250 mg/dL). Bile acid sequestrants should not be used as a single agent in the presence of elevated triglycerides.

HMG CoA reductase inhibitors (lovastatin, pravastatin, fluvastatin, and simvastatin) are very effective for lowering LDL levels in patients who do not tolerate or respond to the first line agents of choice. Fibrates (Gemfibrazil and clofibrate) have moderate effects on LDL levels but are more effective in lowering elevated triglycerides. Combination therapy may be used on high risk patients who fail to respond to diet and single agent medication regimens. Combining a bile acid sequestrant with either nicotinic acid or an HMG CoA reductase inhibitor can markedly lower LDL levels

As a group, statins decrease total and LDL cholesterol levels All statins have a minimal effect in raising HDL levels Atorvastatin is the most effective in reducing LDL However, unlike the more extensively studied agents (e.g., pravastatin, simvastatin), atorvastatin has not been proved to reduce total morbidity and mortality. The most common adverse effects of the statins are gastrointestinal disturbances, headache, myalgias and rash. STATINS

Monitoring The patient should take the statin for at least four weeks before repeating lipid level tests. Recheck lipid levels in three months Muscle aches are the statins' most feared adverse effect

Niacin (Nicotinic Acid) Niacin is the oldest lipid-lowering agent that has been proved to decrease cardiovascular morbidity and total mortality It reduces serum triglyceride, total cholesterol and LDL cholesterol values It also has the beneficial effect of raising HDL levels. An extended-release form of niacin (Niaspan) has the same beneficial lipid-altering effects as standard niacin Although less effective than the statins in decreasing LDL levels, ER niacin can increase HDL values by 20 percent, decrease triglyceride levels by 25 percent

Adverse Effects Flushing is the most common side effect Abdominal pain, nausea and vomiting (all less than 8 percent Avoid concomitant ingestion of alcohol or hot beverages Patients who take extended-release niacin tend to have fewer adverse effects than those who use standard niacin preparations

Monitoring Periodic liver function tests are mandatory Every 12 weeks for the first year and then every six months May promote glucose intolerance Can also increase uric acid levels

TABLE 7 National Cholesterol Education Program (NCEP) Guidelines: Serum Triglyceride Action Limits Triglyceride value Intervention <200 mg per dL Normal value. Some recommend a lower normal value of 150 mg per dL 200 to 400 mg per L Primary treatment is lifestyle modification: weight control, low-fat, low-cholesterol diet, regular exercise, smoking cessation and (in selected patients) alcohol restriction. Medication may be considered in patients with established CHD, family history of premature CHD, concomitant total

total cholesterol level of >=240 mg per dL and HDL value of <35 mg per dL, genetic form of hypertriglyceridemia (e.g., dysbetalipoproteinemia or familial combined hyperlipidemia) or multiple risk factors. 400 to 1,000 mg per dLTreatment as in previous category but with an emphasis on controlling causes of secondary hypertriglyceridemia. Medication is recommended by some authorities and certainly should be used if the patient has a history of acute pancreatitis.

>1,000 mg per dLVigorous triglyceride-lowering efforts are required because of increased risk for pancreatitis. Treat causes of secondary hypertriglyceridemia (e.g., diabetes mellitus). Institute very-low-fat diet, curtail alcohol; if triglyceride level of <1,000 mg per dL is not achieved, use medications.

Fibrates are used to treat hypertriglyceridemia. This class of drugs includes clofibrate (Atromid-S), gemfibrozil (Lopid) and fenofibrate (Tricor) Fibric Acid Derivatives (Fibrates Medication is generally not used to treat hypertriglyceridemia unless fasting serum triglyceride levels are greater than 400 mg per dL Fibrates decrease triglyceride values by 20 to 45 percent and increase HDL levels by 7 to 15 percent.

Adverse Effects Gastrointestinal intolerance (abdominal pain, nausea, vomiting, diarrhea, constipation, dyspepsia) is the most common adverse effect associated with fibrate therapy Neuromuscular (headache, dizziness, vertigo, arthralgias) and dermatologic reactions Incidence of myalgias and rhabdomyolysis increases with concomitant use of a statin Gemfibrozil has been associated with cholelithiasis in 1 percent of the patients Fibrates increase gallbladder and hepatic cholesterol concentrations

Bile Acid Sequestrants Cholestyramine (LoCholest) and colestipol (Colestid) are the two bile acid sequestrants currently available These agents lower LDL (20 percent) and raise HDL (5 percent). Maximal therapeutic effect is evident after one month of therapy.

Adverse Effects Gastrointestinal disturbances Interfere with intestinal absorption of various vitamins and minerals Decrease the absorption of numerous medications, including levothyroxine, penicillin, propranolol, thiazide diuretics and digoxin

Combination regimens should be considered for use in patients who fail to meet target values and are compliant with their current therapy Myopathy and rhabdomyolysis are serious concerns when statins are combined with fibrates or niacin Compliance with bile acid sequestrants is a problem The statins have the best compliance or maintenance rates, followed by niacin, gemfibrozil and bile acid sequestrants

Combination therapy increases the likelihood of reaching target values, but poor compliance is a variable that can foil even the most aggressive therapeutic interventions.

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