Lipoprotein:- Part 2 – Low-Density Lipoprotein (LDL), LDL- Cholesterol (Bad cholesterol)
- This is done in the serum.
- Plasma with EDTA can be used but not with oxalate.
- Get a sample after 12 hours of fast.
- The sample is stable for 1 to 3 days at 4 °C.
Indications for Low-density lipoprotein (LDL)
- To assess lipid profile.
- To assess the risk of heart disease.
- To monitor the therapy in case of abnormal findings.
Pathophysiology of lipoprotein
- Lipids are synthesized in the liver and intestine and then transported to many tissues for their metabolic function.
- The lipids are insoluble, so these are transported as macromolecule complexes called lipoproteins.
- Lipoprotein’s simple structure is explained in the following diagram.
- The outer covering lipoproteins are called Apoproteins and these are classified into:
- Apo- B.
- 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.
- Fats are absorbed from the intestine as chylomicrons which transport the dietary fats to the muscles and the adipose tissue.
Low-density lipoprotein (LDL):
- This is the Cholesterol that is carried in the circulation by LDL (Low-density lipoprotein).
- LDL has a longer half-life of 3 to 4 days than its precursors of VLDL.
- LDL is produced by the liver and intestinal mucosal cells.
- LDL catabolism takes place in the liver and peripheral tissue.
- LDL differs from VLDL because of its lower cholesterol contents, and no C or E apoproteins
Low-density lipoprotein (LDL) consists of :
- Cholesterol = 45%
- Triglycerides = 10%
- Phospholipids = 20%
- Protein = 25%
- Another source (Teitz Fundamental of Clinical Chemistry):
- Cholesterol 8%.
- Cholesterol esters 42%.
- Triglycerides 6%.
- Phospholipids 22%.
- Apoproteins 22%.
Functions of LDL:
- This is called bad cholesterol.
- Most of the cholesterol carried by the LDL is deposited in the lining of the blood vessels.
- LDL increases the risk of atherosclerosis in the coronary arteries (A high level of LDL is atherogenic).
- LDL also causes peripheral vascular disease.
- LDL provides cholesterol to other body cells and leads to atherosclerosis of the vessels.
- LDL levels can be lowered by diet, exercise, and statin.
- LDL is mainly metabolized in the liver.
Normal Low density-protein (LDL)
|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
The risk of coronary artery disease:
|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|
- 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 of LDL
- An elevated level is a major risk factor for atherosclerosis.
Increased LDL values are seen in:
- Familial hyperlipidemia type 2.
- Familial hypercholesterolemia.
- Glycogen storage diseases.
- Secondary causes are :
- Nephrotic syndrome.
- Multiple myelomas.
- Liver disease with obstruction.
- Diabetes mellitus.
- Chronic renal failure.
- Diet high in cholesterol and saturated fats.
- Alcohol intake.
Decreased values are seen in:
- Hyperlipoproteinemia type 1.
- Chronic anemias.
- Hepatocellular diseases.
- Chronic pulmonary disease.
- Reye’s syndrome.
- Acute stress is like a burn.
- Inflammatory joint disease.
NCEP classification of total cholesterol and LDL in adults
|Desirable||< 200 (5.15 mmol/L)||< 130 (3.36 mmol/L)|
|Borderline||200 to 239 (5.15 to 6.18 mmol/L)||130 to 160 (3.36 to 4.11 mmol/L)|
|High||> 240 (6.2 mmol/L)||> 160 (4.14 mmol/L)|
- NCEP = National cholesterol education program.
Adult treatment panel III (ATP III) classification of cholesterol:
- Total cholesterol mg/dL
- Desirable level = < 200 mg/dL
- Borderline level = 200 to 239 mg /dL
- High level = > 240 mg/ dL.
- LDL mg / dL
- Optimal level = <100 mg/ dL.
- Near optimal level = 100 to 129 mg/dL.
- Border line level = 130 to 159 mg/dL.
- High level = 160 to 189 mg /dL.
- Very high level = >190 mg/ dL.
- HDL mg/dL
- Low level = <40 mg / dL.
- High level = >60 mg / dL.
ATP III (Adult treatment panel) recommendations for LDL
|Risk Group||Risk Factors||Target or desirable level of LDL|
|Presence of coronary heart disease (CHD) or CHD-equivalent||If there is coronary heart disease, diabetes, noncoronary atherosclerotic vascular disease,||<100 mg/dL|
|2 or more major risk factors||Major risk factors are: Hypertension (140/90), smoking, F/O premature coronary heart disease, HDL <40||<130|
|>2 major risk factors||Above are the major risk factors||<160 mg/dL|
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|