Lipoprotein disorders
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Lipoprotein Disorders Microchapters |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]
Synonyms and keywords: Dyslipidemia, dyslipoproteinemia, hyperlipidemia
Overview
Lipoproteins, which are aggregates of proteins and lipids, allow the circulation of hydrophobic lipids in the body. Disorders of lipids and lipoproteins metabolism have important health consequences, mainly on the cardiovascular system. Lipoprotein disorders can be described as abnormalities in the level of the lipids, which include cholesterol and triglycerides, or as abnormalities in the levels of lipoproteins that include LDL, HDL, VLDL and chylomicrons.
Lipoprotein disorders have been initially classified in 1967 into different phenotypes by Fredrickson according to the type of lipoproteins that accumulate. However; Fredrickson's classification of hyperlipoproteinemias took into consideration the elevation in chylomicrons, LDL, VLDL but did not include abnormalities in HDL levels. Other classifications have been suggested, one of which is the National Cholesterol Education Program (NCEP) classification of lipoprotein disorders. NCEP classifies lipid disorders according to laboratory cut off points for the levels of total cholesterol, LDL-C and HDL.
Lipoprotein disorders can be classified according to different criteria. First of all, lipoprotein disorders can be classified as primary disorders resulting from genetic mutations and secondary to other diseases. Another way of classifying lipoprotein disorders is as hypolipidemia (or hypolipoproteinemia) and hyperlipidemia (hyperlipoproteinemia) where the lipoprotein levels are decreased and increased respectively. However, the latter classification is not precise and creates some ambiguity, because some people can be labeled as having hyperlipidemia but have simultaneously high level of some lipoproteins and low levels of other lipoproteins depending on the underlying pathophysiology. Hence, a better term to describe the constellation of abnormal lipid profiles is "disorders of lipoproteins", or dyslipoproteinemia or dyslipidemia.
Definitions
In order to understand the different lipoprotein disorders, it is important to correctly define the keywords used to define them.
- Hyperlipidemia: Hyperlipidemia is a commonly used term that describes high level of lipids, whether cholesterol or triglycerides. Despite being commonly used to describe abnormalities in lipid metabolism in our daily practice, this term is not very specific. For instance, people who have metabolic syndrome have high LDL and low HDL and yet they are described to have hyperlipidemia when their HDL level is decreased.
- Hyperlipoproteinemia: Hyperlipoproteinemia is the elevation of lipoproteins, the aggregates of lipids and proteins. Hyperlipoproteinemia is the term used by Fredrickson in his classification of lipoprotein disorders. Hyperlipoproteinemia can be used interchangeably with hyperlipidemia in some instances, however, they are not synonyms. In fact, some lipoprotein disorders can have elevated or decreased level of lipoproteins while the toltal cholesterol level is within normal ranges.
- Dyslipoproteinemia: Dyslipoproteinemia describes abnormalities of lipoproteins. Dyslipoproteinemia reflects the lipoprotein disorders better than hyperlipoproteinemia since is does not limited these disorders only to cases where some types of lipoproteins are elevated.
- Dyslipidemia: Dyslipidemia is the most general term that can describe lipoprotein and lipid disorders since the definition includes variation in the levels of lipoproteins, total cholesterol and triglycerides.
Lipid Profile
The lipid profile measured in daily clinical practice includes the following variables:
- Total cholesterol
- Triglycerides
- HDL cholesterol
- LDL cholesterol, which is calculated by the formula: LDL = Total cholesterol - HDL - (Triglycerides/5)
Formula: Total cholesterol= HDL + LDL + Triglycerides/5
According to the previous formula the measured level of total cholesterol reflects changes in LDL, triglycerides and HDL.
Lipoproteins are composed of a protein part, the apolipoprotein, and the lipid part which includes cholesterol, triglycerides and fatty acids. The lipoproteins differ among each other in terms of density and size as a result of difference in the percentage of each components. While VLDL, chylomicrons and IDL are rich in triglycerides, LDL is rich in cholesterol. Hence, abnormalities in measured lipid levels can be simplified as follows:
- Hypercholesterolemia, defined as high level of measured cholesterol, is reflected by high LDL.
- Hypertriglyceridemia, defined as high level of measured triglycerides, is reflected by high VLDL and/or IDL and/or chylomicrons.
- Combined hyperlipidemia, defined as high levels of measured cholesterol and triglycerides, is due to elevation in both LDL and VLDL and/or IDL and/or chylomicrons.
Classification
There are several ways in which lipoprotein abnormalities are classified. Lipoprotein disorders can be classified according to:
- The pattern of change in the lipoprotein levels, described as hyperlipidemia (increase in lipid levels) and hypolipidemia (decrease in lipid levels): However, this classification is problematic because the lipids and lipoproteins levels in some situation can be elevated in some types of lipoproteins and lipids and decreased in others.
- Phenotype, or the specific type of lipid that is increased, as classified by Fredrickson: This classification is problematic because it does not include abnormalities in the level of HDL.
- Etiology, as primary (genetic) or secondary to another condition: This classification can be problematic, because most conditions involve the intersection of genetics and lifestyle issues. However, there are a few well defined genetic conditions that are usually easy to identify.
- Levels of measured lipids (cholesterol and triglycerides), described as hypercholesterolemia and hypocholesterolemia or hypertriglyceridimia and hypotriglyceridemia: This distinction is not specific because it does not reflect the specific lipoprotein(s) that are abnormally high or low.
Fredrickson Classification of Hyperlipoproteinemia
| Hyperlipoproteinemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type I: Familial hyperchylomicronemia | Type II | Type III: Dysbetalipoproteinemia | Type IV: Primary hypertriglyceridemia | Type V: Mixed hyperlipoproteinemia | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Type A: Familial hypercholesterolemia | Type B: Familial combined hyperlipidemia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type A | Type B | Type C | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Classification According to Etiology
| Lipoprotein Disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary (Genetic) | Secondary | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| LDL | Chylomicron Remnants | Lipoproteins Rich in Triglyceride (Chylomicrons, VLDL, IDL) | HDL | Alcohol Diabetes Drugs Liver disease Obesity Renal disease Smoking Thyroid | |||||||||||||||||||||||||||||||||||||||||||||||||
| High LDL: - Familial hypercholesterolemia - Familial defective apo B 100 - Autosomal dominant hypercholesterolemia (PCSK9) - Autosomal recessive hypercholesterolemia - Familial sistosterolemia - Familial lipoprotein a lipoproteinemia | Low LDL: - Abetalipoproteinemia - Hypobetalipoproteinemia | - Deficiency in hepatic lipase - Type III dysbetalipoproteinemia | - Deficiency in lipoprotein lipase - Deficiency in Apo C-II - Deficiency in Apo A-V - Familial combined hyperlipidemia - Familial hypertriglyceridemia | High LDL: - Cholesteryl ester transferase protein deficiency | Low HDL: - Deficiency in Apo A-I - Tangier disease - Deficiency in lecithin cholesterol acyltransferase (LCAT) - Nieman-Pick disease | ||||||||||||||||||||||||||||||||||||||||||||||||
Classification According to Laboratory Results
| Lipid Laboratory Tests | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Total cholesterol | LDL-C | HDL-C | Triglycerides | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| High total cholesterol | Low total cholesterol | High LDL | Low LDL | High HDL | Low HDL | High triglycerdies | Low triglycerides | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Types
Increases
- Hyperlipoproteinemia: lipoproteins (usually LDL unless otherwise specified)
- Hyperchylomicronemia: chylomicrons
- Combined hyperlipidemia: both LDL and triglycerides
- Familial hypercholesterolemia is a specific form of hypercholesterolemia due to a defect on chromosome 19 (19p13.1-13.3).
Decreases
- Hypolipoproteinemia: lipoproteins
- Hypocholesterolemia: cholesterol
- Abetalipoproteinemia: beta lipoproteins
- Tangier disease: high density lipoprotein