Lipoprotein – Part 2 – Low density lipoprotein (LDL), LDL- Cholesterol (Bad cholesterol)

September 22, 2020Chemical pathologyLab Tests

Sample

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

Indications

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

Pathophysiology

1. Lipids are synthesized in the liver and intestine then transported to various tissue for their metabolic function.
   1. These are insoluble, so these are transported as macromolecules complexes called lipoproteins.
   2. Lipoprotein’s simple structure is explained in the following diagram.

Lipoprotein Structure

1. 3. The outer covering lipoproteins are called Apoprotein and these are classified into:
      1. Apo-1.
      2. Apo-II.
      3. Apo- B.
      4. Apo-D.
      5. Apo-E.
         1. Apolipoproteins are a hydrophilic component of the lipoproteins.
         2. 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 Classification

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

Dietary Transportation of Fats

3. LDL:
   1. 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.

Synthesis of LDL

4. LDL consists of :
   1. Cholesterol 13%
   2. Cholesterol esters 39%
   3. Triglycerides 11%
   4. Phospholipids 17%
   5. Protein 20%
      1. Another source (Teitz Fundamental of Clinical Chemistry):
         1. Cholesterol 8%
         2. Cholesterol esters 42%
         3. Triglycerides 6%
         4. Phospholipids 22%
         5. Apoproteins 22%
            

            Composition of LDL

5. 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 (High level of LDL is atherogenic).
   4. LDL also causes peripheral vascular disease.

Risk of LDL

1. LDL level can be lowered by diet, exercise, and statin.
2. LDL is mainly metabolized in the liver.

Normal

Source 1

LDL-Cholesterol:

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

The risk of coronary artery disease:

• Recommended desirable  = <130 mg/dL
• Moderate risk = 130 to 159 mg/dL
• High risk = ≥ 160 mg/dL

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)

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

Significance

• 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 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   = 10 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