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

June 27, 2024Chemical pathologyLab Tests

Low-Density Lipoprotein (LDL)

What sample is needed 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.

What are the 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.

How will you discuss the 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

Low-Density Lipoprotein (LDL): Lipoprotein structure

  1. 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.
  2. Apolipoproteins are a hydrophilic component of lipoproteins.
  3. Lipids like cholesterol and triglycerides are hydrophobic and need to be placed in water-soluble micellar structures (Apolipoproteins) to be transported in the plasma.
Lipoprotein and apoproteins

Lipoprotein and apoproteins

Lipoprotein separation by electrophoresis on agarose gel

Lipoprotein separation by electrophoresis on agarose gel

  1. Fats are absorbed from the intestine as chylomicrons, which transport the dietary fats to the muscles and the adipose tissue.
Dietary Fat absorption

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 lack of C or E apoproteins.

What are the contents of Low-density lipoprotein (LDL)?

  1. Cholesterol = 45%
  2. Triglycerides = 10%
  3. Phospholipids = 20%
  4. Protein = 25%
Low-density lipoprotein (LDL)

Low-density lipoprotein (LDL)

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

What are the 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

Low-density lipoprotein (LDL) metabolism

  1. LDL increases the risk of atherosclerosis in the coronary arteries (A high LDL level is atherogenic).
  2. LDL also causes peripheral vascular disease.
  3. LDL provides cholesterol to other body cells and leads to atherosclerosis of the vessels.
Low-density lipoprotein (LDL)

Low-density lipoprotein (LDL)

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

What is the normal low-density lipoprotein (LDL)?

Source 1

LDL-Cholesterol:

Age  Male mg/dL  Female mg/dL
 Cord blood 20 to 56 21 to 58
 5 to 9 year 63 to 129 68 to 140
 10 to 14 year 64 to 133 68 to 136
 15 to 19 year 62 to 130 59 to 137
 20 to 24 year 66 to 147 57 to 159
 25 to 29 year  70 to 165 71 to 164
30 to 34 year 78 to 185 70 to 156
35 to 39 year 81 to 189 75 to 172
40 to 44 year 87 to 186 74 to 174
45 to 49 year 97 to 202 79 to 186
50 to 54 year 89 to 197 88 to 201
55 to 59 year 88 to 203 89 to 210
60 to 64 year 83 to 210 100 to 224
65 to 69 year 98 to 210 92 to 221
>70 year 88 to 186 96 to 206
  • To convert into SI unit x 0.0259 = mmol/L

What is the risk of coronary artery disease based on Low-Density Lipoprotein (LDL)?

Risk for coronary heart disease LDL level
  • Desirable LDL
  • <130 mg/dL (3.36 mmol/L)
  • Border-line risk  of LDL
  • 130 to 159 mg/dL (3.36 to 4.11 mmol/L)
  • High-risk LDL
  • ≥160 mg/dL

Another source of Low-Density Lipoprotein (LDL) safe values:

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

How will you calculate Low-density-lipoprotein (LDL)?

The following formula can calculate the LDL:

  • 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

LDL-cholesterol calculation formula

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

What is the significance of Low-Density Lipoprotein (LDL?

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

What are the conditions where you will see increased Low-Density Lipoprotein (LDL)?

  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. A diet high in cholesterol and saturated fats.
    9. Alcohol intake.
    10. Hepatoma.

What conditions will you see decreased Low-Density Lipoprotein (LDL)?

  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.

What is the relationship between NCEP classification of total cholesterol and LDL in adults for coronary disease?

Category Total cholesterol LDL-cholesterol
  • Desirable
  • < 200 mg/dL (5.15 mmol/L)
  • < 130 mg/dL (3.36 mmol/L)
  • Borderline (High-risk)
  • 200 mg/dL to 239 mg/dL (5.15 to 6.18 mmol/L)
  • 130 mg/dL  to 160 mg/dL (3.36 to 4.11 mmol/L)
  • High Risk
  • > 240 mg/dL  (6.2 mmol/L)
  • > 160 mg/dL (4.14 mmol/L)
  • NCEP = National Cholesterol Education Program.

How will you explain Adult Treatment Panel III (ATP III) for the 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.

What are ATP III (Adult Treatment Panel) recommendations for Low-Density Lipoprotein (LDL)?

Risk Group Risk Factors  Target or desirable level of LDL
Presence of coronary heart disease (CHD) or CHD-equivalent
  1. If there is coronary heart disease
  2. Diabetes
  3. Noncoronary atherosclerotic vascular disease,
  <100 mg/dL
 2 or more major risk factors  Major risk factors are:

  1. Hypertension (140/90)
  2. Smoking
  3. F/O premature coronary heart disease
  4. HDL <40
 <130
 >2 major risk factors Above are the major risk factors <160 mg/dL

How will you summarize the characteristics of the lipoproteins?

Characteristics Chylomicron HDL LDL VLDL
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 the liver to adipose tissue

Questions and answers:

Question 1: What is the risk of LDL for coronary artery disease?
Question 2: What will happen to LDL in hyperthyroidism?
Possible References Used
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