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

Low-Density Lipoprotein (LDL)

Sample for Low-Density Lipoprotein (LDL)

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 fasting.
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 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. The liver and intestinal mucosal cells produce LDL.
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 the following:

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 Low-Density Lipoprotein (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.
   1. LDL molecules are taken into the cell through LDL receptors.
   2. Once inside the cells, LDL is metabolized into its components.
   3. One of the components, cholesterol, is partly used by the cells and partly goes out into the blood circulation.
   4. LDL through cholesterol has an atherogenic role.

Low-density lipoprotein (LDL) metabolism

3. LDL increases the risk of atherosclerosis in the coronary arteries (A high LDL level 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)

6. LDL levels can be lowered by diet, exercise, and statin.
7. 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 based on Low-Density Lipoprotein (LDL):

Another source of Low-Density Lipoprotein (LDL) (safe value)

• 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 Low-Density Lipoprotein (LDL)

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

Increased Low-Density Lipoprotein (LDL) values are seen in the following:

1. Familial hyperlipidemia type 2.
2. Familial hypercholesterolemia.
3. Glycogen storage diseases.
4. The 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 Low-Density Lipoprotein (LDL) values are seen in the following:

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 for coronary disease:

• 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 Low-Density Lipoprotein (LDL)

Table showing the summary of characteristics of the lipoproteins:

Questions and answers: