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Hyperlipoproteinemia
Background
Hyperlipoproteinemia is a metabolic disorder characterized by abnormally elevated concentrations of
specific lipoprotein particles in the plasma.
Pathophysiology
Hyperlipidemia (ie, elevated plasma cholesterol or triglyceride levels or both) is present in all
hyperlipoproteinemias. The primary form includes chylomicronemia, hypercholesterolemia,
dysbetalipoproteinemia, hypertriglyceridemia, mixed hyperlipoproteinemia, and combined
hyperlipoproteinemia. Other diseases, such as diabetes mellitus, pancreatitis, renal disease, and
hypothyroidism, cause the secondary form.
Epidemiology
Frequency
United States
This condition has a high frequency in developed countries.
Mortality/Morbidity
If uncontrolled, higher mortality occurs from cardiovascular and cerebrovascular diseases.
Abnormalities of the vascular system can develop, including ischemic cardiac disease. Obtaining
appropriate medical evaluation is important, especially in patients younger than 40 years who have a
prominent corneal arcus, xanthelasma, or lipemia retinalis.
Race
African Americans are affected more frequently than whites.
Sex
No sexual preponderance exists.
Age
Hyperlipoproteinemia may be present in children and young adults but is seen more frequently in later
life.
History
Clinical manifestations of the hyperlipoproteinemias are caused by the deposition of lipids in the
vascular system and the eye.
Physical
Corneal arcus, lipemia retinalis, and xanthelasma are the most common ocular abnormalities.[1]
Lipemia retinalis is primarily caused by an elevation of the serum triglyceride levels, which imparts a
milky color to the blood.
The changes are usually not seen until the triglyceride level reaches at least 2000 mg/dL in the early
stages; they are best observed in the peripheral fundus. The vessels initially appear salmon-pink, but,
when the triglyceride level rises further, they become whitish.
These changes, which begin in the periphery, progress toward the posterior pole as the triglyceride
level rises. In severe cases, the vessels are creamy white, and differentiating the arteries from the veins
is difficult. The findings can fluctuate widely from day to day, depending on the triglyceride level.
The fundus abnormalities, which improve as the triglyceride levels return to normal, provide a method of following the patient's course and response to therapy. Xanthelasma is a deposition of lipid in the eyelid, usually the upper medial lid. The lesions may be excised, but recurrences are common. With primary excisions, recurrences of up to 40% have been reported, and secondary excision recurrences are even higher. Of the initial failures, 20% are within the first year. Causes Risks appear to include diet, stress, physical inactivity, and smoking. Differential Diagnoses Xanthelasma Laboratory Studies Measure plasma lipid and lipoprotein levels while the patient is on a regular diet after an overnight fast of 12-16 hours. Abnormal lipoprotein patterns can often be identified after determining serum cholesterol and triglyceride levels and visual inspection of the plasma sample (stored at 4°C). In some cases, performing electrophoresis and ultracentrifugation of whole plasma specimens may be necessary to help establish a diagnosis. Imaging Studies Ophthalmologists generally do not order imaging studies. Medical Care Systemic Drugs are used to lower cholesterol and triglyceride levels. Because of the possibility of adverse effects and the question of whether the triglyceride level is an independent risk factor for atherosclerosis, many physicians use drugs to reduce the triglyceride level only when the level exceeds 500 mg/100 mL. Examples of these drugs include lovastatin, pravastatin, and simvastatin. A study by Shimabukuro et al found that the impact on lipoprotein subclass profiles varies between pitavastatin and atorvastatin. Determining the lipoprotein subclass profile and selecting the appropriate statin in patients with diabetes and an additional cardiovascular risk, such as low HDL cholesterol or hypertriglyceridemia may be beneficial.[2] Supportive Weight reduction and a diet low in saturated fat and cholesterol are advocated. Patients should avoid alcohol and estrogen in certain types of hyperlipoproteinemias. Surgical Care Ileal bypass surgery and plasmapheresis to lower elevated serum lipids are used in selected cases of familial hypercholesterolemia. Only experienced physicians should use these therapies. Consultations Internist or family practitioner Diet A low-fat diet is recommended, including fruit, vegetables, chicken, and fish. Medication Summary Drugs are used to lower cholesterol and triglyceride levels. Because of the possibility of adverse effects and the question of whether the triglyceride level is an independent risk factor for atherosclerosis, many physicians use drugs to reduce the triglyceride level only when the level exceeds 500 mg/100 mL.[3, 4, 5] HMG-CoA reductase inhibitors Class Summary These agents are competitive inhibitors of 3-hydroxy-3-methyl Co-A reductase, an enzyme that catalyzes the rate-limiting step in cholesterol biosynthesis, resulting in up-regulation of LDL receptors in response to the decrease in intracellular cholesterol. The HMG-CoA reductase inhibitors are indicated for the secondary prevention of cardiovascular events and for the treatment of hypercholesterolemia and mixed dyslipidemia. A number of HMG-CoA reductase inhibitors are indicated for patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments. However, these agents may be less effective in patients with rare homozygous familial hypercholesterolemia, possibly because these patients are lacking functional LDL receptors, making it more likely to raise serum transaminases. Pravastatin (Pravachol) Lipid-lowering compound; HMG-CoA reductase inhibitor; reduces cholesterol biosynthesis; orally administered in active form; rapidly absorbed (peak plasma 1-1.5 h). Therapeutic response is usually 1 wk. Highly effective in reducing total-C, LDL-C, and triglycerides in patients with heterozygous familial, presumed familiar forms of primary hypercholesterolemia, and mixed dyslipidemia. View full drug information Lovastatin (Mevacor, Altocor) This is a cholesterol-lowering agent, isolated from a strain of Aspergillus terreus. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol. Available in immediate-release (Mevacor) and sustained-release (Altocor) dosage forms. View full drug information Simvastatin (Zocor) Inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme in an early and rate-limiting step in the synthetic pathway of cholesterol. Peak plasma 1.3-2.4 h; peak antilipemic effects 3-4 mo. Rosuvastatin (Crestor) HMG-CoA reductase inhibitor, which, in turn, decreases cholesterol synthesis and increases cholesterol metabolism. Reduces total-C, LDL-C, and TG levels and increases HDL-C level. Used adjunctively with diet and exercise to treat hypercholesterolemia. Nicotinic acid derivatives Class Summary Niacin (vitamin B-3) inhibits the hepatic secretion of VLDL cholesterol. Niacin is effective in most categories of hyperlipidemia. Niacin has been demonstrated to lower LDL cholesterol by 32%, lower triglycerides by 20-50%, and raise HDL cholesterol by 43%. Niacin lowers lipoprotein (a) levels, which may be of some clinical importance because lipoprotein (a) levels have been associated with coronary heart disease in numerous epidemiological studies. The clinical benefit of lowering lipoprotein (a) levels has not been determined. Niacin (Nicobid, Niaspan, Nicotinex) Niacin functions in the body after conversion to nicotinamide adenine dinucleotide (NAD) in the NAD coenzyme system. Niacin in gram doses reduces total cholesterol, LDL-C, and triglycerides and increases high-density lipoprotein cholesterol. The magnitude of individual lipid and lipoprotein responses may be influenced by the severity and type of underlying lipid abnormality. Niacin should be taken at bedtime after a low-fat snack and individualized according to patient response. Further Outpatient Care With this chronic condition, long-term follow-up care is important.[6] Periodic blood lipid levels are imperative. Inpatient & Outpatient Medications Most cases are controlled with diet, exercise, and medication. Patient Education For excellent patient education resources, see eMedicineHealth's Cholesterol Center. Also, visit eMedicineHealth's patient education articles High Cholesterol, Cholesterol Charts, Lifestyle Cholesterol Management, and Cholesterol-Lowering Medications.

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