Lipoprotein disorders overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hardik Patel, M.D.

Lipoprotein Disorders Microchapters
Patient Information
Overview
Causes
Classification Hyperlipoproteinemia Hypolipoproteinemia
Treatment

Overview

Hyperlipidemia is the presence of raised or abnormal levels of lipids and/or lipoproteins in the blood. Lipids (fatty molecules) are transported in a protein capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence on metabolism. Hyperlipidemia can occur as either a primary event or secondary to some underlying disease. The primary hyperlipidemias are associated with overproduction and/or impaired removal of lipoproteins. The latter defect can be induced by an abnormality in either the lipoprotein itself or in the lipoprotein receptor.

Lipid and lipoprotein abnormalities are extremely common in the general population, and are regarded as a highly modifiable risk factor for cardiovascular disease due to the influence of cholesterol, one of the most clinically relevant lipid substances, on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.

Classification

Hyperlipidemias are classified according to the Fredrickson classification which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation. It was later adopted by the World Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions. It remains a popular system of classification, but is considered dated by many.

Pathophysiology

Hyperlipidemia can occur as either a primary event or secondary to some underlying disease. The primary hyperlipidemias are associated with overproduction and/or impaired removal of lipoproteins. The latter defect can be induced by an abnormality in either the lipoprotein itself or in the lipoprotein receptor.

Causes

Hyperlipidemias are caused by primary and secondary causes. Primary hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor protein)such as chylomicronemia, hypercholesterolemia, dysbetalipoproteinemia, hypertriglyceridemia, mixed hyperlipoproteinemia, and combined hyperlipoproteinemia, while secondary hyperlipidemia arises due to other underlying causes such as diabetes. Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a modifiable risk factor for cardiovascular disease due to their influence on atherosclerosis. In addition, some forms may predispose to acute pancreatitis.

Differentiating Hyperlipidemia from other Diseases

Several conditions, such as 27-hydroxylase, deficiency and sitosterolemia produce tendon xanthomas that are similar to those produced by several types of hyperlipidemia. However, these occur with normal cholesterol levels and, therefore, can be easily differentiated from hyperlipidemia.

Epidemiology and Demographics

Hyperlipidemia is a common health problem that tends to more often affect the elderly population in developed countries. It is a major cause of disease burden globally as a risk factor for cardiovascular and cerebrovascular diseases.

Risk Factors

There is an increased risk of hyperlipidemia in certain groups of patients. Some of these risks are age (males ≥ age 45 and females ≥ age 55), family history of premature coronary artery disease; definite myocardial infarction (MI) or sudden death before age 55 in father or other male first-degree relative, or before age 65 in mother or other female first-degree relative, cigarette smoking, hypertension, diabetes mellitus and body mass index > 30.

Screening

Screening and treatment of lipid disorders in people at high risk for future coronary heart disease (CHD) events has been recommended by the, United States Preventive Services Task Force (USPSTF) especially for patients with known CHD. However, the role of screening in people with low to medium risk is controversial. On the basis of the effectiveness of treatment, the availability of accurate and reliable tests, and the likelihood of identifying people with abnormal lipids and increased CHD risk, screening appears to be effective in middle-aged and older adults and in young adults with additional cardiovascular risk factors.

Natural History, Complications and Prognosis

Hyperlipidemia may be inherited or secondary to some underlying disorder. Without treatment, it progresses to cause cardiovascular and cerebrovascular diseases. However, early detection and aggressive management to lower the blood lipid levels helps prevent complications.

Diagnosis

History and Symptoms

Hyperlipidemia itself usually does not produce any symptoms and discovered during routine screening. Family history of premature coronary heart disease and severe hyperlipidemia may be present in primary hyperlipidemias. Patient may have symptoms consistent with its complications.

Physical Examination

Hyperlipidemias, particularly familial hypercholesterolemia and familial defective apoB-100 are commonly associated with the findings of xanthoma, xanthelasma and corneal arcus on physical examination.

Laboratory Findings

Complete fasting lipid profile should be obtained for making the diagnosis of hyperlipidemia and risk stratification for coronary heart diseases. In the absence of symptoms or signs suggestive of a particular disorder, a limited workup should also be performed to rule out secondary hyperlipidemias.

Treatment

Medical Therapy

Hyperlipidemia requires early detection, careful evaluation and aggressive treatment with combination of therapeutic lifestyle changes and lipid-lowering drug therapies to reduce the risk of cardiovascular and cerebrovascular complications.

Prevention

Screening and treatment of lipid disorders in people at high risk for future coronary heart disease (CHD) events has been recommended by the, 'United States Preventive Services Task Force (USPSTF)' especially for patients with known CHD. However, the role of screening in people with low to medium risk is controversial. On the basis of the effectiveness of treatment, the availability of accurate and reliable tests, and the likelihood of identifying people with abnormal lipids and increased CHD risk, screening appears to be effective in middle-aged and older adults and in young adults with additional cardiovascular risk factors.

Future or Investigational Therapies

Gene therapy to manipulate the LDL-receptor (LDLR) gene is still at an experimental stage. Initially, expectations were high that genetic manipulation would be a less hazardous and more effective method for providing functional LDL-receptors compared with liver transplantation. However, progress in the development of gene therapy has been slow.

References

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