High, Low, and Very Low Density Lipoproteins

Lipoproteins are considered to be an accurate predictor of heart disease. As part of the lipid profile, these tests are performed to identify persons at risk for developing heart disease and to monitor therapy if abnormalities are found.

 

Lipoproteins are proteins in the blood whose main purpose is to transport cholesterol, triglycerides, and other insoluble fats. They are used as markers indicating the levels of lipids within the bloodstream. Lipoproteins can be classified by their measured density.
General categories of lipoproteins, listed in order from larger and less dense (more fat than protein) to smaller and denser (more protein, less fat) are as follows:
• Chylomicrons—carry triacylglycerol (fat) from the intestines to the liver, skeletal muscle, and to adipose tissue.
• Very low–density lipoproteins (VLDL)—carry (newly synthesized) triacylglycerol from the liver to adipose tissue.
• Intermediate-density lipoproteins (IDL)—are intermediate between VLDL and LDL. They are not usually detectable in the blood.
• Low-density lipoproteins (LDL)—carry cholesterol from the liver to cells of the body. Sometimes referred to as the “bad cholesterol” lipoprotein.
• High density lipoproteins (HDL)—collects cholesterol from the body’s tissues (and vascular endothelium) and brings it back to the liver. Removing lipids from the endothelium (reverse cholesterol transport) provides a protective effect against heart disease. Therefore HDL is referred to as the “good cholesterol” lipoprotein.
The “lipid profile” usually measures total Cholesterol, Triglycerides, HDL, LDL, and VLDL. Through the use of Segmented Gradient Gel Electrophoresis (SGGE), lipoproteins could be subclassified to more accurately indicate cardiovascular risks and familial risks of heart disease. Levels of lipoproteins are genetically influenced; however, these levels can be altered by diet, lifestyle, and medications.

 

Clinical and epidemiologic studies have shown that total HDL cholesterol is an independent, inverse risk factor for coronary artery disease (CAD). Low levels (<35 mg/dL) are believed to increase a person’s risk for CAD, while high levels (>60 mg/dL) are considered protective. When HDL and total cholesterol measurements are combined in a ratio fashion, the accuracy of predicting CAD is increased. The total cholesterol/HDL ratio should be at least 5:1, with 3:1 being ideal.

 

SGGE identified five subclasses of HDL (2a, 2b, 3a, 3b, and 3c), but only 2b is cardioprotective. HDL 2b is the most efficient form of HDL in reverse cholesterol transport. Patients with low total HDL levels often have low levels of HDL 2b. When levels of total HDL are between 40 and 60, cardioprotective levels of HDL 2b are minimal. However, when levels of total HDL are greater than 60, levels of HDL 2b predominate, and efficient reverse cholesterol transport takes place. This protects the coronary arteries from disease. The other subclasses of HDL are not capable of reverse cholesterol transport and therefore are not cardioprotective. Levels of HDL 2b can be increased by niacin supplements but not by statins (i.e., HMG-CoA reductase inhibitors [simvastatin, lovastatin]).
LDLs (“bad” cholesterol) are also cholesterol rich. However, most cholesterol carried by LDLs can be deposited into the lining of the blood vessels and is associated with an increased risk for arteriosclerotic heart and peripheral vascular disease. Therefore, high levels of LDLs are atherogenic. Target LDL levels vary according to the risk profile of the patient. For example, the optimal LDH level should be less than 70 mg/dL in patients at high risk for heart disease. The LDL level can be calculated using a modified Friedwald formula:

LDL = Total Cholestrol – ( Triglycerides ÷ 5) – HDL

 

There are other formulas for deriving LDL, which may account for different sets of normal values. The formula is inaccurate if the triglycerides exceed 400 mg/dL. More recently, laboratory chromogenic methods in which various detergents are used to separate out LDL allow for a more accurate measurement of LDL. This method uses a unique detergent to solubilize only the non-LDL lipoprotein particles and a second detergent solubilizes the remaining LDL particles, which are then measured by a chromogenic coupler that provides color formation.
With the use of SGGE, LDL has been divided into seven classes based on particle size. These subclasses include (from largest to smallest) LDL I, LDL IIa, LDL IIb, LDL IIIa, LDL IIIb, LDL IVa, and LDL IVb. The most commonly elevated forms of LDL (IIIa and IIIb) are small enough to get between the endothelial cells and cause atheromatous disease. The larger LDL particles (LDL I, LDL IIa, and LDL IIb) cannot get into the endothelial layer and therefore are not associated with increased risk for disease. LDL IVa and IVb, however, are very small and are associated with aggressive arterial plaques that are particularly vulnerable to ulceration and vascular occlusion. Nearly all patients with levels of LDL IVa and IVb greater than 10% of total LDL have vascular events within months.
LDL patterns can be identified, and they are associated with variable risks of coronary artery disease (CAD). LDL pattern A is seen in patients with mostly large LDL particles and does not carry increased risks for CAD. LDL pattern B is seen in patients with mostly small LDL particles and is associated with an increased risk for CAD. An intermediate pattern is noted in a large number of patients; they have small and large LDL particles and experience an intermediate risk for CAD. LDL levels can be lowered with diet, exercise, and statins.
VLDLs, though carrying a small amount of cholesterol, are the predominant carriers of blood triglycerides. To a lesser degree, VLDLs are also associated with an increased risk for CAD because they can be converted to LDL by lipoprotein lipase in skeletal muscle. The VLDL value is sometimes expressed as a percentage of total cholesterol. Levels in excess of 25% to 50% are associated with increased risk for coronary disease.
The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management. The goal for high-risk patients (those with known coronary artery disease or > 2 risk factors) is an LDL lower than 70 mg/dL. All ATP reports have identified low-density lipoprotein cholesterol (LDL-C) as the primary target of cholesterol lowering therapy. Many prospective studies have shown that high serum concentrations of LDL-C are a major risk factor for coronary heart disease (CHD). Moreover, lowering LDL-C levels will reduce the risk for major coronary events.

 

The World Health Organization (WHO) adopted the Fredrickson classification of lipid disorders to identify particular lipoprotein patterns (phenotypes) that are associated with certain inherited or acquired diseases or syndromes. Fredrickson’s classification, through the use of electrophoresis, simply identifies which lipoproteins are raised.

 

There are a variety of methods used to measure the lipoprotein classes. All require serum separation, usually by ultracentrifugation. In the past, lipoproteins were measured through the use of electrophoresis. Immunologic, catalase reagent, and chemical kits are now available for accurately quantifying lipoproteins.

 

 

 

Normal High-Density Lipoproteins Levels

Males tend to normally Have lower HDL Levels than females. The following are the Normal HDL levels for both Genders:

Males: More than 45 mg/dL

Females: More than 55 mg/dL.

 

 

Using HDL Levels to Indicate the Risk of Heart Disease

High-Density Lipoproteins Levels can indicate the risk of Heart Disease. The risk of Heart Disease increases as HDL Levels decrease. The following are the Heart Disease risk indications of HDL levels for both genders:

 

Males:

Low Heart Disease Risk: 60 mg\dL.

Moderate Heart Disease Risk: Around 45 mg/dL.

High Heart Disease Ristk: 25 mg/dL.

 

Females:

Low Heart Disease Risk: 70 mg\dL.

Moderate Heart Disease Risk: Around 55 mg/dL.

High Heart Disease Ristk: 35 mg/dL.

 

 

 

Normal Low-Density Lipoproteins Levels

Low Density Lipoproteins should be found in low levels within a person who has a healthy heart. Children normally have lower LDL levels than Adults. The following are the Normal LDL levels for both Children and Adults:

 

Children: Less than 110 mg/dL.

Adults: Less than 130 mg/dL.

 

 

 

Normal Very Low-Density Lipoproteins Levels

Very Low-Density Lipproteins are like LDLs, they should be found in low levels within a  person who has a healthy heart. Normal VLDL Levels range between 7 and 32 mg/dL.

 

 

 

Causes of Lipoproteins Levels False Indications

  • Smoking and Alcohol ingestion decrease HDL levels.
  • Binge eating can alter lipoprotein values.
  • HDL values are age- and sex-dependent.
  • HDL values, like cholesterol, tend to decrease significantly for as long as 3 months following Myocardial Infarction (MI).
  • HDL is elevated in patients with Hypothyroid and Diminished in those with Hyperthyroid.
  • High triglyceride levels can cause inaccurate calculations of LDL.

 

The following Drugs may cause altered lipoprotein levels:

  • Beta blockers: Increase Triglycerides, decrease HDL-C, decrease LDL size, decrease HDL 2b.
  • Alpha-blockers: Decrease Triglycerides, increase HDL-C, increase LDL size, increase HDL 2b
  • Dilantin increases HDL-C.
  • Steroids (in general) increase Triglycerides
  • Estrogens increase Triglycerides.

 

 

 

Causes of High HDL Levels

  • Familial HDL lipoproteinemia: Genetically, the patient is predetermined to have high HDL levels.
  • Excessive exercise: HDL can rise with chronic exercise for 30 minutes three times a week. When the exercise greatly exceeds that minimum, HDL can become significantly elevated.

 

 

 

Causers of Low HDL Levels

  • Metabolic syndrome: This syndrome is associated with an atherogenic lipid profile (ALP) that includes decreased HDL, increased triglycerides, elevated fasting glucose, high blood pressure, and abdominal obesity measured by waist circumference.
  • Familial low HDL: Genetically, the patient is predetermined to have low HDL levels. As a result, these patients are at high risk for CHD.
  • Hepatocellular disease (e.g., hepatitis, cirrhosis): HDL is made in the liver. Without liver function, HDL is not made and levels fall.
  • Hypoproteinemia (e.g., nephrotic syndrome, malnutrition): With loss of proteins, HDL is not made and levels fall. When the hypoproteinemia is severe, however, and oncotic pressures fall, the production of lipoproteins could be stimulated and actually rise. Elevation of HDL occurs only late in the disease.

 

 

 

Causes of High LDL and VLDL Levels

  • Familial LDL lipoproteinemia: Genetically, the patient is predetermined to have high LDL levels.
  • Nephrotic syndrome: The loss of proteins diminishes the plasma oncotic pressures. This appears to stimulate hepatic lipoprotein synthesis of LDL and possibly to diminish lipoprotein disposal of the same.
  • Glycogen storage diseases (e.g., von Gierke disease): VLDL synthesis is increased and excretion is diminished. VLDL and LDL levels rise.
  • Hypothyroidism: VLDL and LDL catabolism is diminished. VLDL and LDL levels rise. This is a common cause of lipid abnormalities, especially among women.
  • Alcohol consumption: Hyperlipidemias are known to occur in persons who drink excessive quantities of alcohol. However, there also may be a genetic factor associated with this observation.
  • Chronic liver disease (e.g., hepatitis, cirrhosis): The liver catabolizes LDL. Without that catabolism, blood levels increase.
  • Hepatoma: The normal inhibition of LDL synthesis by eating dietary fats does not occur. LDL synthesis continues unabated. LDL levels rise.
  • Gammopathies (e.g., multiple myeloma): High levels of gamma globulins (IgG and IgM) attach to the VLDL and LDL molecule and thereby decrease their catabolism.
  • Familial hypercholesterolemia type IIa: LDL receptors are altered, and LDL is produced at increased rates.
  • Cushing syndrome: VLDL synthesis is increased. VLDL is converted to LDL.
  • Apoprotein CII deficiency: This genetic defect is associated with a deficiency of lipoprotein lipase. As a result, VLDL and other lipoproteins (chylomicrons) accumulate.

 

 

 

Decreased LDL and VLDL

  • Familial hypolipoproteinemia: Genetically, the patient is predetermined to have low VLDL or LDL levels.
  • Hypoproteinemia (e.g., malabsorption, severe burns, malnutrition): Early in the course of this process, LDLs are low. However, later the LDL and VLDL levels can actually rise.
  • Hyperthyroidism: Catabolism of LDL and VLDL is increased and levels fall.