Lipoprotein:- Part 2 – Low-Density Lipoprotein (LDL), LDL- Cholesterol (Bad cholesterol)

June 7, 2022Chemical pathologyLab Tests

Sample

1. This is done in the serum.
2. Plasma with EDTA can be used but not with oxalate.
3. Get a sample after 12 hours of fast.
4. The sample is stable for 1 to 3 days at 4 °C.

Indications for Low-density lipoprotein (LDL)

1. To assess lipid profile.
2. To assess the risk of heart disease.
3. To monitor the therapy in case of abnormal findings.

Pathophysiology of  lipoprotein 

1. Lipids are synthesized in the liver and intestine and then transported to many tissues for their metabolic function.
   1. The lipids are insoluble, so these are transported as macromolecule complexes called lipoproteins.
   2. Lipoprotein’s simple structure is explained in the following diagram.

Low-Density Lipoprotein (LDL): Lipoprotein structure

2. 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.
3. Apolipoproteins are a hydrophilic component of lipoproteins.
4. 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.

Lipoprotein and apoproteins

Lipoprotein separation by electrophoresis on agarose gel

5. Fats are absorbed from the intestine as chylomicrons which transport the dietary fats to the muscles and the adipose tissue.

Dietary Fat absorption

Low-density lipoprotein (LDL):

1. This is the Cholesterol that is carried in the circulation by LDL (Low-density lipoprotein).
2. LDL has a longer half-life of 3 to 4 days than its precursors of VLDL.
3. LDL is produced by the liver and intestinal mucosal cells.
4. LDL catabolism takes place in the liver and peripheral tissue.
5. LDL differs from VLDL because of its lower cholesterol contents, and no C or E apoproteins

Low-density lipoprotein (LDL) consists of :

1. Cholesterol = 45%
2. Triglycerides = 10%
3. Phospholipids = 20%
4. Protein = 25%

Low-density lipoprotein (LDL)

5. Another source (Teitz Fundamental of Clinical Chemistry):
   1. Cholesterol 8%.
   2. Cholesterol esters 42%.
   3. Triglycerides 6%.
   4. Phospholipids 22%.
   5. Apoproteins 22%.

Functions of LDL:

1. This is called bad cholesterol.
2. Most of the cholesterol carried by the LDL is deposited in the lining of the blood vessels.
3. LDL increases the risk of atherosclerosis in the coronary arteries (A high level of LDL is atherogenic).
4. LDL also causes peripheral vascular disease.
5. LDL provides cholesterol to other body cells and leads to atherosclerosis of the vessels.

Low-density lipoprotein (LDL)

5. LDL levels can be lowered by diet, exercise, and statin.
6. LDL is mainly metabolized in the liver.

Normal Low density-protein (LDL)

Source 1

LDL-Cholesterol:

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

The risk of coronary artery disease:

Another source

• Adult  =  <130 mg/dL
• Children  =  <110 mg/dL

Calculation of LDL

The LDL can be calculated by the following formula:

• LDL = Total cholesterol – X
  • X = (Triglycerides ÷ 5) – HDL
  • LDL = Total cholesterol – ([triglycerides ÷ 5] – HDL)
• Another formula is :
  • LDL = Total cholesterol – HDL-chol – X
  • X = Triglycerides ÷ 5
• OR  LDL = Total cholesterol — (HDL cholesterol + 1/5 x Triglycerides)

LDL-cholesterol calculation formula

NOTE: These formulas only help if the fasting triglycerides value is < 400 mg/ dl.

Significance of LDL

• An elevated level is a major risk factor for atherosclerosis.

Increased LDL values are seen in:

1. Familial hyperlipidemia type 2.
2. Familial hypercholesterolemia.
3. Glycogen storage diseases.
4. Secondary causes are :
   1. Hypothyroidism.
   2. Nephrotic syndrome.
   3. Multiple myelomas.
   4. Dysglobulinemia.
   5. Liver disease with obstruction.
   6. Diabetes mellitus.
   7. Chronic renal failure.
   8. Diet high in cholesterol and saturated fats.
   9. Alcohol intake.
   10. Hepatoma.

Decreased values are seen in:

1. Hypolipoproteinemia.
2. Hyperthyroidism.
3. Hyperlipoproteinemia type 1.
4. Chronic anemias.
5. Hepatocellular diseases.
6. Chronic pulmonary disease.
7. Reye’s syndrome.
8. Acute stress is like a burn.
9. Inflammatory joint disease.

NCEP classification of total cholesterol and LDL in adults

• NCEP = National cholesterol education program.

Adult treatment panel III (ATP III) classification of cholesterol:

• Total cholesterol mg/dL

1. Desirable  level  =  < 200 mg/dL
2. Borderline level  =  200 to 239 mg /dL
3. High level           =  > 240 mg/ dL.

• LDL mg / dL 

1. Optimal level          = <100 mg/ dL.
2. Near optimal level   = 100 to 129 mg/dL.
3. Border line level      =  130 to 159 mg/dL.
4. High level                =  160 to 189 mg /dL.
5. Very high level        =  >190 mg/ dL.

• HDL mg/dL

1. Low level               = <40 mg / dL.
2. High level              =  >60 mg / dL.

ATP III (Adult treatment panel) recommendations for LDL

Table showing the summary of characteristics of the lipoproteins