Lipoprotein: – Part 1 – High-Density Lipoprotein (HDL), HDL-Cholesterol (HDL-C), Lipoprotein
High-Density Lipoprotein (HDL)
- This test is done on the serum.
- A fasting sample is preferred. Advised the patient to fast for 12 to 14 hours.
- This test can be done on plasma as well.
- Can store serum or plasma at 4 °C for 4 days (can keep for 5 to 7 days).
Precautions for High-Density Lipoprotein (HDL)
- Don’t use oxalate, fluoride, citrate, or heparin for the collection of the blood.
- HDL values are age and sex-related.
- HDL value is increased in Hypothyroidism and decreased in Hyperthyroidism.
- Drugs that increase the value are oral contraceptives, aspirin, phenothiazine, steroids, and sulphonamides.
- Smoking and alcohol decrease HDL value.
Purpose of the test (Indications) for High-Density Lipoprotein (HDL)
- Advised to evaluate coronary artery disease risk.
- This can be advised as part of a lipid profile.
Pathophysiology of Lipoproteins
- Lipoproteins are insoluble so these are transported in the plasma as a macromolecular complex.
- Lipoproteins are sphericle particles with:
- Nonpolar lipids are triglycerides and free cholesterol.
- Polar lipids are phospholipids and free cholesterol.
- Lipoprotein is classified by electrophoresis on the basis of its physical and chemical structure as follows:
- These are primarily triglycerides.
- These are the vehicle where lipids are absorbed from the intestine and able to enter the bloodstream.
- Beta-lipoprotein These are primary carriers of cholesterol.
- It arises primarily from the degradation of VLDL into LDL1 and it was called intermediate-density lipoprotein (IDL).
- LDL-1 is short-lived and it is converted into LDL-2.
- LDL-2 will remove some of the triglycerides load.
- LDL is a membrane protein.
- There are tissue receptors on the cells, which are engulfed by the cells and degraded by the lysosomal enzymes.
- It is Pre-beta – lipoproteins, these are mainly triglycerides.
- It originates in the liver and transports triglycerides from the liver to other tissues.
- α–Lipoproteins, are mainly proteins with a small amount of cholesterol.
- It arises from the liver and intestine and contains primarily both apolipoproteins A-I and A-II.
- It is a cholesterol scavenger and removes cholesterol from the tissues.
- HDL will esterify cholesterol and carries it to the liver for removal.
- HDL converts cholesterol into bile acids and excretion into bile.
- The outer covering lipoproteins are called Apoproteins and these are classified into:
- Apo- B.
|Apolipoproteins||Type of lipoprotein||Molecular mass in Da|
|Apo A-IV||It is secreted with chylomicron and transferred to HDL||46,000|
- Apolipoproteins are a hydrophilic component of lipoproteins.
- 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.
- In the case of endogenous pathways, the lipoproteins are synthesized in the liver from carbohydrates and fats.
Summary of the lipoproteins:
|Type of lipoprotein||Apoprotein contents||Electrophoresis pattern||The main type of lipids||% of Apoprotein||Origin tissue||Functions|
High-density lipoprotein (HDL):
- HDL cholesterol is synthesized and secreted into the liver and intestine.
- This can be separated by electrophoresis and ultracentrifugation.
- HDL is composed of phospholipids and apolipoprotein (Apo A-1 and Apo – A-II), these are almost 90% of the total protein.
- The ratio of Apo – A-1 to Apo – A-11 is ∼ 3:1 by weight.
- HDL from the intestine does not contain Apo-C or Apo-E and only contains Apo-A.
- The dominant Apoprotein is Apo-A I (67%) and it is followed by A-II, C, and E.
- This may be responsible for the transport of dietary cholesterol.
- HDL plays a role in the transportation of cholesterol to the liver from the tissue where it is excreted in the bile.
- HDL transports cholesterol to the liver where cholesterol serves as the precursor of the bile acids or part of the VLDL component.
- While lipoproteins transport cholesterol, triglycerides, and other insoluble fats.
- HDL (Composition) consists of:
- Cholesterol = 6%.
- Cholesterol ester = 13%.
- Triglycerides = 3%.
- Phospholipids = 28%.
- Protein = 50%.
- HDL has very few triglycerides.
- There is a high percentage of proteins, phospholipids, and cholesterol.
- Another source says:
- Triglycerides = 5%
- Cholesterol = 15%
- Phospholipids = 30%
- Proteins = 50%
- The ratio of esterified and free cholesterol is 3:1.
- The decreased level of HDL is atherogenic.
- HDL Raised level protects against atherosclerosis by removing the cholesterol from the arteries and taking it to the liver.
- 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.
- HDL-C is good cholesterol and is proportional to coronary artery disease (CAD) risk.
- When there is high cholesterol with a high level of HDL, the treatment is not indicated.
Functions of High-density lipoprotein (HDL) function:
- HDL is the carrier of cholesterol from the peripheral tissue.
- From peripheral tissue, HDL carries cholesterol to the liver for excretion in the bile known as reverse cholesterol transport.
- HDL has a protective role by preventing cellular uptake of cholesterol and lipids.
- HDL protects against cardiovascular diseases.
Table showing HDL and its relationship with coronary heart disease
|Risk of heart disease||Male||Female|
|Low||60 mg/dL HDL||70 mg/dL HDL|
|Moderate||45 mg/dL HDL||55 mg/dL HDL|
|High||25 mg/dL HDL||35 mg/dL HDL|
The total cholesterol/HDL-cholesterol ratio:
- It is the ratio that is very important to know the risk of coronary heart disease.
- A high ratio is associated with increased risk.
- The normal ratio should be at least 5:1 and the best is 3:1.
Total cholesterol/HDL-cholesterol Ratio Risk for Coronary disease
|Above-average x 2 times||7.0||9.6|
|Above-average x 3 times||11.0||23.4|
- HDL-cholesterol level of 70 mg/dl or greater is associated with longevity of life.
Normal High-density lipoprotein (HDL):
|Age||Male mg/dL||Female mg/dL|
|Cord blood||6 to 53||13 to 56|
|5 to 9 year||38 to 75||36 to 73|
|10 to 14 year||37 to 74||37 to 70|
|15 to 19 year||30 to 63||35 to 74|
|20 to 24 year||30 to 63||33 to 79|
|25 to 29 year||31 to 63||37 to 83|
|30 to 34 year||28 to 63||36 to 77|
|35 to 39 year||29 to 62||34 to 82|
|40 to 44 year||27 to 67||34 to 88|
|45 to 49 year||30 to 64||34 to 87|
|50 to 54 year||28 to 63||37 to 92|
|55 to 59 year||28 to 71||37 to 91|
|60 to 64 year||30 to 74||38 to 92|
|65 to 69 year||30 to 75||35 to 96|
|>70 year||31 to 75||33 to 92|
- To convert into SI unit x 0.0259 = mmol/L
- Male = >50 mg/dL
- Female = >55 mg/dL
- 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:
|HDL value||Risk for the coronary disease (CAD)|
|<25 mg/dL||CAD risk is 2 times and is a dangerous level|
|26 to 35 mg/dL||CAD risk is 1.5 times. This is a high-risk group|
|36 to 454 mg/dL||CAD risk is 1.2 times. This moderate risk group|
|45 to 59 mg/dL||This is an average risk group|
|>60 mg/dL||Below average risk group|
Increased HDL-C value seen in:
- When it is >60 mg/dL.
- Chronic liver diseases like cirrhosis, hepatitis, and alcoholism.
- Long-term vigorous exercises.
- Familial hyper- alpha-lipoproteinemia.
- The increased level may be due to some drugs.
- Estrogen therapy.
- Moderate intake of alcohol.
- Insulin therapy.
Decreased HDL-C values are seen in:
- When it is <40 mg/dL.
- Poorly controlled diabetes
- Chronic renal failure, uremia, and nephrotic syndrome.
- Familial hypo-alpha-lipoproteinemia.
- alpha and beta – lipoproteinemia.
- The decreased level may also be seen in some of the drugs.
- Antihypertensive drugs.
- Secondary causes are:
- Stress and recent illnesses like AMI, stroke, and surgery.
- Starvation and a nonfasting sample are 5% to 10% lower.
- Diabetes mellitus.
- Liver diseases.
- Uremia and nephrosis.
Table showing the summary of characteristics of the lipoproteins
|PLasma appearance||Creamy layer, slightly turbid||Clear||Clear, or yellow-orange tint||Turbid to opaque|
|Size (diameter nm)||>70.0||4 to 10||19.6 to 22.7||25 to 70|
|Electrophoretic mobility||Origin||α – region||β – region||Pre – β region|
|Molecular weight||0.4 to 30 x 109||3.6 x 109||2.75 x 109||5 to 10 x 109|
|Synthesized in (Tissue of origin)||Intestine||Intestine and liver||Intravascular||Liver and intestine|
|Composition by weight in %|
|Cholesterol esterified||5||38||49||11 to 14|
|Cholesterol unesterified||2||10||13||5 to 8|
|Triglycerides||84||9||11||44 to 60|
|Phospholipids||7||22||27||20 to 23|
|Proteins||2||21||23||4 to 11|
|Triglycerides||Markedly raised||Normal||Normal/ Raised||Moderately to Markedly raised|
|Clinical significance of||Pancreatitis and acute abdomen||Decreased risk of CAD||Increased risk of CAD||Increased risk of CAD|
|Functions||Transport dietary lipids to tissue||Carry cholesterol from tissue to liver||Carries cholesterol to tissue||Transport endogenous TG from liver to adipose tissue|