1. HYPERLIPIDEMIA Applied Therapeutics Dr. Riyadh Mustafa Al-Salih

2. DEFINITION Hyperlipidemia is defined as an elevation of one or more of the following: cholesterol, cholesterol esters, phospholipids, or triglycerides. Hyperlipoproteinemia describes an increased concentration of the lipoprotein macromolecules that transport lipids in the plasma. Abnormalities of plasma lipids can result in a predisposition to coronary, cerebrovascular, and peripheral vascular arterial disease.

3. PATHOPHYSIOLOGY Cholesterol, triglycerides, and phospholipids are transported in the bloodstream as complexes of lipid and proteins known as lipoproteins. Elevated total and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol are associated with the development of coronary heart disease (CHD).

4. PATHOPHYSIOLOGY The response-to-injury hypothesis states that risk factors such as oxidized LDL, mechanical injury to the endothelium, excessive homocysteine, immunologic attack, or infection-induced changes in endothelial and intimal function lead to endothelial dysfunction and a series of cellular interactions that culminate in atherosclerosis. The eventual clinical outcomes may include angina, myocardial infarction, arrhythmias, stroke, peripheral arterial disease, abdominal aortic aneurysm, and sudden death.

5. CLINICAL PRESENTATION Familial hypercholesterolemia is characterized by a selective elevation in plasma LDL and deposition of LDL-derived cholesterol in tendons (xanthomas) and arteries (atheromas).

6. DIAGNOSIS A fasting lipoprotein profile (FLP) including total cholesterol, LDL, HDL, and triglycerides should be measured in all adults 20 years of age or older at least once every 5 years.

7. DESIRED OUTCOME The goals of treatment are to lower total and LDL cholesterol in order to reduce the risk of first or recurrent events such as myocardial infarction, angina, heart failure, ischemic stroke, or other forms of peripheral arterial disease such as carotid stenosis or abdominal aortic aneurysm.

8. TREATMENT  GENERAL PRINCIPLES The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) recommends that a fasting lipoprotein profile and risk factor assessment be used in the initial classification of adults. If the total cholesterol is less than 200 mg/dL, then the patient has a desirable blood cholesterol level. If the HDL is also above 40 mg/dL, no further follow-up is recommended for patients without known CHD and who have fewer than two risk factors.

9. TREATMENT In patients with borderline-high blood cholesterol (200 to 239 mg/dL), assessment of risk factors is needed to more clearly define disease risk. There are three categories of risk that modify the goals and modalities of LDL-lowering therapy. The highest risk category is having known CHD or CHD risk equivalents; the risk for major coronary events is equal to or greater than that for established CHD (i.e., more than 20% per 10 years, or 2% per year). The intermediate category includes two or more risk factors, in which the 10-year risk for CHD is 20% or less. The lowest risk category is persons with zero to one risk factor, which is usually associated with a 10-year risk of CHD of less than 10%.

10. NONPHARMACOLOGIC THERAPY TLCs are begun on the first visit and include dietary therapy, weight reduction, and increased physical activity. Inducing a weight loss of 10% should be discussed with patients who are overweight. In general, physical activity of moderate intensity 30 minutes a day for most days of the week should be encouraged. All patients should be counseled to stop smoking and to meet (JNC 7) guidelines for control of hypertension.

11. PHARMACOLOGIC THERAPY 1. Bile Acid Resins (Cholestyramine, Colestipol, Colesevelam) 2. Niacin 3. HMG-CoA Reductase Inhibitors (Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, Rosuvastatin, Simvastatin) 4. Fibric Acids (Gemfibrozil, Fenofibrate, Clofibrate) 5. Ezetimibe 6. Fish Oil Supplementation