High-Density Lipoprotein (HDL)

Sample

1. This test is done on the serum.
2. A fasting sample is preferred. Advised the patient to fast for 12 to 14 hours.
3. This test can be done on plasma as well.
4. Can store serum or plasma at 4 °C for 4 days (can keep for 5 to 7 days).

Precautions for High-Density Lipoprotein (HDL)

1. Don’t use oxalate, fluoride, citrate, or heparin for the collection of the blood.
2. HDL values are age and sex-related.
3. HDL value is increased in Hypothyroidism and decreased in Hyperthyroidism.
4. Drugs that increase the value are oral contraceptives, aspirin, phenothiazine, steroids, and sulphonamides.
5. Smoking and alcohol decrease HDL value.

Purpose of the test (Indications) for High-Density Lipoprotein (HDL)

1. Advised to evaluate coronary artery disease risk.
2. This can be advised as part of a lipid profile.

Pathophysiology of Lipoproteins 

1. Lipoproteins are insoluble so these are transported in the plasma as a macromolecular complex.
2. Lipoproteins are sphericle particles with:
   1. Nonpolar lipids are triglycerides and free cholesterol.
   2. Polar lipids are phospholipids and free cholesterol.

3. Lipoprotein is classified by electrophoresis on the basis of its physical and chemical structure as follows:
   1. Chylomicron:
      1. These are primarily triglycerides.
      2. These are the vehicle where lipids are absorbed from the intestine and able to enter the bloodstream.
   2. LDL:
      1.  Beta-lipoprotein These are primary carriers of cholesterol.
      2. It arises primarily from the degradation of VLDL into LDL1 and it was called intermediate-density lipoprotein (IDL).
      3. LDL-1  is short-lived and it is converted into LDL-2.
      4. LDL-2 will remove some of the triglycerides load.
      5. LDL is a membrane protein.
      6. There are tissue receptors on the cells, which are engulfed by the cells and degraded by the lysosomal enzymes.
   3. VLDL:
      1. It is Pre-beta – lipoproteins, these are mainly triglycerides.
      2. It originates in the liver and transports triglycerides from the liver to other tissues.
   4. HDL:
      1. α–Lipoproteins, are mainly proteins with a small amount of cholesterol.
      2. It arises from the liver and intestine and contains primarily both apolipoproteins A-I and A-II.
      3. It is a cholesterol scavenger and removes cholesterol from the tissues.
         1. HDL will esterify cholesterol and carries it to the liver for removal.
         2. HDL converts cholesterol into bile acids and excretion into bile.

4. The outer covering lipoproteins are called Apoproteins and these are classified into:
   1. Apo-1.
   2. Apo-II.
   3. Apo- B.
   4. Apo-D.
   5. Apo-E.

5. Apolipoproteins are a hydrophilic component of lipoproteins.
6. While lipids like cholesterol and triglycerides are hydrophobic and need to be placed in water-soluble micellar structures (Apolipoproteins)  in order to be transported in the plasma.

7. In the case of endogenous pathways, the lipoproteins are synthesized in the liver from carbohydrates and fats.

High-density lipoprotein (HDL):

1. HDL cholesterol is synthesized and secreted into the liver and intestine.
2. This can be separated by electrophoresis and ultracentrifugation.
3. HDL is composed of phospholipids and apolipoprotein (Apo A-1 and Apo – A-II), these are almost 90% of the total protein.
4. The ratio of Apo – A-1 to Apo – A-11 is ∼ 3:1 by weight.
   1. HDL from the intestine does not contain Apo-C or Apo-E and only contains Apo-A.
5. The dominant Apoprotein is Apo-A I (67%) and it is followed by A-II, C, and E.
6. This may be responsible for the transport of dietary cholesterol.
7. HDL plays a role in the transportation of cholesterol to the liver from the tissue where it is excreted in the bile.
   1. HDL transports cholesterol to the liver where cholesterol serves as the precursor of the bile acids or part of the VLDL component.
   2. While lipoproteins transport cholesterol, triglycerides, and other insoluble fats.
8. HDL (Composition) consists of:
   1. Cholesterol = 6%.
   2. Cholesterol ester = 13%.
   3. Triglycerides = 3%.
   4. Phospholipids = 28%.
   5. Protein  = 50%.
      1. HDL has very few triglycerides.
      2. There is a high percentage of proteins, phospholipids, and cholesterol.
9. Another source says:
   1. Triglycerides = 5%
   2. Cholesterol = 15%
   3. Phospholipids = 30%
   4. Proteins = 50%

9. The ratio of esterified and free cholesterol is 3:1.
10. The decreased level of HDL is atherogenic.
    1. HDL Raised level protects against atherosclerosis by removing the cholesterol from the arteries and taking it to the liver.
    2. HDL and LDL may combine to maintain cellular Cholesterol balance through the mechanism of LDL moving cholesterol into the arteries and HDL removing it from the arteries.
    3. HDL-C is good cholesterol and is proportional to coronary artery disease (CAD) risk.

11. When there is high cholesterol with a high level of HDL, the treatment is not indicated.

Functions of High-density lipoprotein (HDL) function:

1. HDL is the carrier of cholesterol from the peripheral tissue.
2. From peripheral tissue, HDL carries cholesterol to the liver for excretion in the bile known as reverse cholesterol transport.
3. HDL has a protective role by preventing cellular uptake of cholesterol and lipids.
4. HDL protects against cardiovascular diseases.

Table showing HDL and its relationship with coronary heart disease

The total cholesterol/HDL-cholesterol ratio:

1. It is the ratio that is very important to know the risk of coronary heart disease.
2. A high ratio is associated with increased risk.
3. The normal ratio should be at least 5:1 and the best is 3:1.

 Total cholesterol/HDL-cholesterol Ratio Risk for Coronary disease

• HDL-cholesterol level of 70 mg/dl or greater is associated with longevity of life.

Normal High-density lipoprotein (HDL):

Source 1

HDL-Cholesterol

• To convert into SI unit x 0.0259 = mmol/L

Source 2

HDL

• Male = >50 mg/dL
• Female = >55 mg/dL

Another source

HDL

• Men= 36 to 65 mg/dl or > 45 mg/dl (>0.75 mmol/L).
• Women= 35 to 80 mg/dl or > 55 mg/dl (>0.91 mmol/L).

Abnormal values of HDL:

Increased HDL-C value seen in:

1. When it is >60 mg/dL.
2. Chronic liver diseases like cirrhosis, hepatitis, and alcoholism.
3. Long-term vigorous exercises.
4. Familial hyper- alpha-lipoproteinemia.
5. The increased level may be due to some drugs.
   1. Estrogen therapy.
   2. Moderate intake of alcohol.
   3. Insulin therapy.
6. Hypobetalipoproteinemia.

Decreased HDL-C values are seen in:

1. When it is <40 mg/dL.
2. Poorly controlled diabetes
3. Cholestasis.
4. Chronic renal failure, uremia, and nephrotic syndrome.
5. Hypertriglyceridemia.
6. Familial hypo-alpha-lipoproteinemia.
7. alpha and beta – lipoproteinemia.
8. The decreased level may also be seen in some of the drugs.
   1. Steroids.
   2. Antihypertensive drugs.
   3. Diuretics.
   4. Beta-blockers.
   5. Thiazide.
9. Secondary causes are:
   1. Stress and recent illnesses like AMI, stroke, and surgery.
   2. Starvation and a nonfasting sample are 5% to 10% lower.
   3. Diabetes mellitus.
   4. Hypothyroidism.
   5. Liver diseases.
   6. Uremia and nephrosis.

Table showing the summary of characteristics of the lipoproteins