Overview:
Hyperlipidemias are characterized by high levels of lipids in the blood (hyper = elevated, lipid, emia = blood).
Hyperlipidemia is often asymptomatic, but it significantly increases one's risk for cardiovascular diseases, especially
atherosclerosis.
Two commonly used systems of classification:
– The older scheme, which focuses on inherited lipidemias, is called the
Fredrickson Classification system.
– The newer system divides lipidemias according to
primary (aka, genetic) or
secondary (aka, acquired) causes.
– Primary lipidemias can be exacerbated by secondary causes.
Comprise proteins and phospholipids that transport cholesterol and triglycerides in the body.
Outer surface of a lipoprotein:
– Apolipoprotein = protein that binds lipids.
There are several types of apolipoproteins, some of which are implicated in hyperlididemias, as we'll soon see.
– Phospholipids and free cholesterol.
Core:
– Triglycerides (aka, triacylglycerol)
– Cholesterol esters
Chylomicrons deliver dietary triglycerides and cholesterol to the liver and peripheral tissues.
Chylomicron remnants are produced when triglycerides are removed from chylomicrons; thus, they are rich in cholesterol esters.
Very Low Density Lipoproteins (VLDL) are made in the liver, and are rich in triglycerides.
Intermediate Density Lipoproteins (IDL) are produced when triglycerides are removed from VLDL; thus, like the chylomicron remnants, they are rich in cholesterol.
Because they are formed from VLDL, Intermediate Density Lipoproteins are sometimes referred to as VLDL remnants.
Low Density Lipoproteins are produced after even more triglycerides are removed from the Very Low Density Lipoproteins and their remnants; thus, LDL is very rich in cholesterol, which it carries to the peripheral tissues.
LDL is sometimes referred to as
"bad" cholesterol, because it distributes cholesterol throughout the body and vessels. In the vessels, the deposited cholesterol contributes to obstructive plaque formation and atherosclerosis.
High Density Lipoproteins (HDL), which are part of the
reverse cholesterol transport pathway, carry cholesterol from the peripheral tissues to the liver.
In addition to removing excess cholesterol, High Density Lipoproteins have various other anti-atherogenic properties, so it they are often referred to as
"Good" cholesterol.
Hypercholesterolemia is often defined as:
- Total cholesterol > 200 mg/dL
- Low-Density Lipoproteins > 130 mg/dL
- High-Density Lipoproteins < 40 mg/dL
Hypertriglyceridemia = levels above 150 mg/dL.
Xanthomas
These are created by lipid deposits in the skin associated with
foam cells (macrophages that have ingested lipids).
Tuberous xanthomas form small to large bulges in the skin over the
joints, particularly the elbows and knees.
Eruptive xanthomas are
erythematous bumps that tend to appear on the buttocks, shoulders, and extensor surfaces.
Plane xanthomas are thin yellow plaques. Xanthelasma is characterized by plaques around the
eyelids.
Palmar xanthomas are characterized by yellow plaques that form along the creases of the palm of the hands.
Tendinous xanthomas are bumps that form over the
tendons or ligaments
The Achilles tendon at the posterior ankle is a common site for these xanthomas.
Primary hyperlipidemias and their associated Fredrickson Phenotypes
Be aware that there is variation in the names of these disorders.
Hyperchylomicronemia (Fredrickson Type I)
Occurs when there is a deficiency in lipoprotein lipase or an alteration in apolipoprotein C-II, which activates lipoprotein lipase.
These deficiencies cause elevated chylomicrons and triglyceride levels exceeding 500 mg/dL.
This disorder is associated with acute pancreatitis, eruptive xanthomas, and, when triglyceride levels are exceedingly high, lipemia retinalis.
Hypercholesterinemia (Type IIa)
Occurs when LDL receptors are deficient.
Results in elevated Low-Density Lipoproteins and cholesterol.
There are heterozygous and homozygous forms.
Patients are at increased risk of premature Atherosclerotic Cardiovascular Disease (ASCVD), tendinous xanthomas, and, corneal arcus, which is a whitish ring around the iris.
Hyperlipidemia (Type IIb)
Occurs when there is a reduction in LDL receptors or increased apolipoprotein B.
Characterized by elevated Low Density Lipoproteins and Very Low Density Lipoproteins.
Both triglycerides and cholesterol are also elevated.
Patients are at increased risk of premature ASCVD and may have tendinous xanthomas.
This is the most common inherited dyslipidemia.
Dysbetalipoproteinemia
Also called hyperlipoproteinemia, Type III
Occurs when apolipoprotein E-2 is defective.
The disorder is characterized by elevated chylomicron remnants and Intermediate Density Lipoproteins (hence, this disorder is sometimes called Remnant Removal Disease).
Both triglyceride and cholesterol levels are elevated.
Patients are at increased risk of ASCVD, and may have palmar xanthoma and/or tuberoeruptive xanthomas of the elbows and knees.
Hypertriglyceridemia (Type IV)
Characterized by increased production and decreased secretion of Very Low Density Lipoproteins.
Elevated levels of triglycerides.
Patients are at increased risk for acute pancreatitis and ASCVD.
Type IV is another relatively common inherited hyperlipidemia.
Mixed hypertriglyceridemia (Type V)
Associated with increased Very Low Density Lipoprotein production and decreased Low Density Lipoprotein production.
Characterized by elevations in chylomicron remnants and VLDL.
Increased triglyceride and cholesterol levels.
Patients are at risk for acute pancreatitis, eruptive xanthomas, and ASCVD.
These factors can also exacerbate primary lipid disorders.
The most significant contributors in the United States are diets high in saturated fats, cholesterol, and trans fats, coupled with sedentary lifestyles.
High levels of alcohol consumption also elevate lipid levels.
Several other disorders may contribute to hyperlipidemia, including: diabetes mellitus, chronic kidney disease, nephrotic syndrome, hypothyroidism, cholestatic liver diseases, and Cushing syndrome.
Several drugs can cause hyperlipidemia, including oral contraceptives, diuretics, beta-blockers, and antiretroviral agents.