eMedicine Specialties > Ophthalmology > Metabolic Disorders

Hyperlipoproteinemia

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Updated: Aug 14, 2007

Introduction

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.

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.

Clinical

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.
• 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

Other Problems to Be Considered

Differentiate the primary and secondary forms of hyperlipoproteinemia.

Workup

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.

Treatment

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.
• 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

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.

HMG-CoA reductase inhibitors

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.

Dosing

Adult

10, 20, and 40 mg tab: Initially 10-20 mg PO hs; prior to dosing, establish lipid and liver functions and recheck at intervals of no less than 4 wk

Pediatric

<18 years: Not recommended

Interactions

Effects increase with cholestyramine; increases toxicity of gemfibrozil, clofibrate, niacin, cyclosporine, and oral anticoagulants; itraconazole and ketoconazole increase toxicity of lovastatin; concurrent use with erythromycin may increase risk of rhabdomyolysis

Contraindications

Documented hypersensitivity; active liver disease

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Tell the patient to report promptly any unexplained muscle pain, tenderness, or weakness, especially if accompanied with malaise or fever

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.

Dosing

Adult

Immediate-release: 20 mg PO qd with evening meal initially; may increase gradually to 20-80 mg/d in single or divided doses
Sustained-release: 10-20 mg PO hs initially; may increase dose q4wk, not to exceed 60 mg/d

Pediatric

Not established

Interactions

Cyclosporine or other immunosuppressants; possible risk of polymyositis and rhabdomyolysis with erythromycin, gemfibrozil, and niacin; high risk of hepatotoxicity, avoid concomitant use with ethanol; oral anticoagulants may enhance clinical effects

Contraindications

Patients with active liver disease or unexplained elevations of serum transaminases; patients receiving immunosuppressive drugs; patients taking itraconazole, ketoconazole, gemfibrozil, niacin, erythromycin, clarithromycin, or nefazodone

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Liver function profiles of 6-12 wk of therapy; use cautiously in patients who consume large amounts of alcohol; renal failure; may contribute to progression of cataracts; monitor patients closely

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.

Dosing

Adult

Initially 5-10 mg PO qd pm; adjust dose every 4 wk per patient tolerance response; not to exceed 40 mg

Pediatric

Not established

Interactions

Drugs that decrease levels or activity of endogenous steroids may increase risk of developing endocrine dysfunction; erythromycin, fibric acid derivatives, immunosuppressants, and high doses of niacin may increase risk of rhabdomyolysis, monitor closely if patient is taking cyclosporine and limit daily dose to 10 mg/d; ethanol increases risk of hepatotoxicity; warfarin may enhance effect; monitor patient at start of therapy and during dosage adjustments

Contraindications

Documented hypersensitivity; patients with active liver disease or conditions that cause unexplained persistent elevations of serum transaminase

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Use cautiously in patients who consume alcohol or who have liver or kidney disease; use only when patient diet and nonpharmacologic therapies have failed; test liver function as therapy starts and periodically thereafter; instruct patients to notify the doctor of adverse reactions and muscle aches and pains

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.

Dosing

Adult

5-10 mg PO qd initially; may increase dose if needed, not to exceed 40 mg/d; for marked hypercholesterolemia (ie, LDL-C >190 mg/dL), initiate with 20 mg/d PO
Familial hypercholesterolemia: 20 mg PO qd initially; may increase dose if needed, not to exceed 40 mg/d

Pediatric

Not established

Interactions

Cyclosporine or gemfibrozil significantly increase C_max and AUC, thereby increasing myopathy and rhabdomyolysis risk; limit dose to 5 mg/d when coadministered with cyclosporine and 10 mg/d when coadministered with gemfibrozil; coadministration with aluminum and magnesium hydroxide antacids decreases plasma concentrations (administer antacids 2 h after rosuvastatin); may increase oral contraceptive plasma concentrations; alcohol may increase hepatotoxic risk

Contraindications

Documented hypersensitivity; active liver disease; unexplained serum transaminase elevation

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Common adverse effects include muscle aches, stomach pain, constipation, nausea, and weakness; may cause myopathy, rhabdomyolysis, and kidney failure; monitor LFTs (ie, baseline, 12 wk after drug initiation and any dose elevation, and semiannually), discontinue if elevation persists; decrease dose with CrCl <30 mL/min; doses 40 mg or greater associated with hematuria and proteinuria

Nicotinic acid derivatives

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.

Dosing

Adult

Initially, dosage is gradually increased, starting with 375 mg and increasing until the patient responds
Recommended maintenance dose is 1000-2000 mg qd

Pediatric

Not established

Interactions

May produce false elevations in some fluorometric determinations of plasma or urinary catecholamines; may potentiate the effects of ganglionic blocking agents and vasoactive drugs causing hypotension; concomitant aspirin may decrease the metabolic clearance of nicotinic acid

Contraindications

Documented hypersensitivity; unexplained hepatic dysfunction; active gastric ulcer disease; arterial bleeding

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus

Precautions

Closely observe patients with history of jaundice, hepatobiliary disease, or peptic ulcer; patients with diabetes may experience a dose-related rise in glucose intolerance; use cautiously in patients with angina; may cause an increase in prothrombin time; avoid with anticoagulants

Follow-up

Further Outpatient Care

• With this chronic condition, long-term follow-up care is important.
• 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 eMedicine's Cholesterol Center. Also, visit eMedicine's patient education articles High Cholesterol, Understanding Your Cholesterol Level, Lifestyle Cholesterol Management, and Understanding Cholesterol-Lowering Medications.

Miscellaneous

Medicolegal Pitfalls

• Early detection may prevent later problems.

References

1. Bron AJ. Corneal changes in the dislipoproteinaemias. Cornea. 1989;8(2):135-40. [Medline].

2. Brownstein S, Jackson WB, Onerheim RM. Schnyder's crystalline corneal dystrophy in association with hyperlipoproteinemia: histopathological and ultrastructural findings. Can J Ophthalmol. Aug 1991;26(5):273-9. [Medline].

3. Crispin SM. Lipid deposition at the limbus. Eye. 1989;3 (Pt 2):240-50. [Medline].

4. Feldman EB. Nutrition and diet in relation to hyperlipidemia and atherosclerosis. In: Shields M, Olson JA, Shike M. Modern Nutrition in Health and Disease. 8^th ed. 1992.

5. Gronemeyer A, Arsene S, Le Lez ML, Rateau J. [Central retinal artery occlusion or branch retinal artery occlusion in the young associated with high lipoprotein (a) levels]. J Fr Ophtalmol. Sep 2002;25(7):727-30. [Medline].

6. Jünemann A, Küchle M, Naumann GO. Epithelial iron line in juvenile corneal arcus lipoides. Cornea. Sep 1995;14(5):540-2. [Medline].

7. Wu CW, Lin PY, Liu YF, Liu TC, Lin MW, Chen WM, et al. Central corneal mosaic opacities in Schnyder's crystalline dystrophy. Ophthalmology. Apr 2005;112(4):650-3. [Medline].

Keywords

hyperlipidemia, chylomicronemia, hypercholesterolemia, dysbetalipoproteinemia, hypertriglyceridemia, mixed hyperlipoproteinemia, combined hyperlipoproteinemia, high cholesterol

Contributor Information and Disclosures

Author

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology
Disclosure: Nothing to disclose.

Medical Editor

Vytautas A Pakainis, MD, Chief of Ophthalmology, Dorn Veterans Administration Medical Center, Professor of Ophthalmology, Ophthalmology, University of South Carolina School of Medicine
Vytautas A Pakainis, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and South Carolina Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles
Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology
Disclosure: Nothing to disclose.

Managing Editor

Steve Charles, MD, Director of Charles Retina Institute; Clinical Professor, Department of Ophthalmology, University of Tennessee College of Medicine
Steve Charles, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Retina Specialists, Macula Society, and Retina Society
Disclosure: Alcon Laboratories Consulting fee Consulting

CME Editor

Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri
Disclosure: Nothing to disclose.

Chief Editor

James P Gills, MD, Founder, St Luke's Cataract and Laser Institute; Professor, Department of Ophthalmology, University of South Florida College of Medicine
James P Gills, MD is a member of the following medical societies: American Academy of Ophthalmology
Disclosure: Nothing to disclose.

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