Cholesterol (Serum Cholesterol)
Sample
- The best sample is after 12 hours of fast, and that is the morning sample.
- The best sample is serum and separated within 2 hours of the collection.
- This test may be done on Serum or Plasma (EDTA) but not oxalate, citrate, or fluoride.
- The serum is stable at 4 °C for 5 to 7 days and 3 months at -20 °C.
- Avoid freezing and thawing.
- The result with EDTA plasma is 3% lower than serum.
- Sample with Cholesterol above 500 mg/dL should be diluted.
Precautions
- Try to separate serum or plasma from the cells within 2 hours.
- The best sample is after 12 to 14 hours of fast.
- Pregnancy may give a high level.
- Drugs that may increase the level are anabolic steroids, corticosteroids, oral contraceptives, vitamin D, phenytoin, thiazide diuretics, and cyclosporin.
- Drugs that may decrease the level are captopril, colchicine, erythromycin, isoniazid (INH), lovastatin, neomycin, bile salt binding agents, androgens, niacin, and nitrates.
Purpose of the test (Indications)
- Cholesterol level is estimated to determine the coronary artery disease risk.
- This test may be needed to rule out hyperlipidemia.
Pathophysiology
- Cholesterol is the best-known steroids because of its association with atherosclerosis.
- Cholesterol has biochemical significance because this is the precursor for important steroids like bile acids, adrenocortical hormones, sex-hormones, Vitamin D, cardiac glycosides, sitosterol of the plant kingdom, and some alkaloids.
- Cholesterol is steroid alcohol with 27 carbon atoms.
- Cholesterol is present virtually in all cells and body fluids.
- Cholesterol is absorbed in the diet and synthesized in the liver and gut.
- It is a precursor of steroid hormone, bile acids, sex hormones, and cellular membranes.
- Cholesterol is present in the diet, mostly from the animal source, and absorbed by the gastrointestinal tract.
- Another source is endogenous, like the liver and other tissues.
- All the cells have the ability to synthesize cholesterol, and 90% occur in the liver and intestines.
- Malnutrition will give low cholesterol formation.
- Another source is endogenous, like the liver and other tissues.
- Cholesterol in the body and their calculation for LDL-cholesterol formula:
- Three different lipoproteins carry cholesterol in the fasting serum. So the total sum of cholesterol is equal to the sum of these three components.
- Total cholesterol = HDL-cholesterol + VLDL-cholesterol + LDL-cholesterol
- The amount of cholesterol in the HDL fraction can be found by precipitating from the serum.
- The level of cholesterol in VLDL = Triglycerides/5
- This formula works in the fasting sample and when:
- The triglycerides are <400 mg/dL.
- No chylomicrons are seen.
- Does not work in type III dyslipidemia (β-VLDL).
- This formula works in the fasting sample and when:
- LDL – cholesterol = The separation of LDL from the lipoproteins is very difficult, so the Friedewald equation is used, which is:
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- LDL-cholesterol = (Total cholesterol mg/dL) – (HDL-cholesterol mg/dL) – (triglycerides mg/dl)/5.
- LDL-cholesterol = (Total cholesterol mg/dL) – (HDL-cholesterol mg/dL) – (triglycerides mg/dl)/5.
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- Cholesterol changes in the body and its distribution along with other lipoproteins:
- There is day to day variation in the cholesterol level.
- This day to day variation may be in a person around 15%.
- An 8% difference can be found on the same day.
- There is a positional change in the level.
- The level may be decreased by as much as 15% in the recumbent position.
- There is a low level in the hospitalized patient.
- Because of these variations, two samples must be tested for heart disease risk.
- There is a decreased level of cholesterol in acute MI as much as 50% for 6 to 8 weeks.
Cholesterol distribution in other lipoproteins:
Type of lipoprotein | Cholesterol | Triglycerides | Phospholipids | Proteins |
Chylomicron | 3% to 5% | 85% to 95% | 5% to 10% | 1% to 2% |
HDL (High-density lipoprotein) | 20% | Very small amount | 30% | 50% |
LDL (Low-density lipoprotein) | 45% | 5% to 10% | 20% to 30% | 15% to 25% |
VLDL (Very-low-density lipoprotein) | 10% to 15% | 60% to 70% | 10% to 15% | 10% |
- Cholesterol absorption:
- The main source of cholesterol is diet. Another source is endogenous.
- Cholesterol is an important constituent in the assembly of the cell membrane.
- Cholesterol is the basic part of the synthesis of bile acids, steroids hormones (cortisol, estrogen, and androgen).
- In the normal biologic process, cholesterol undergoes changes like synthesis, recycling, and degradation.
- The cholesterol enters the intestine from the following sources:
- For food like egg yolk, meat, fat-diary products, and seafood, the average amount is 400 to 700 mg/day.
- Plant sterols (200 to 300 mg) are ingested daily. These are poorly absorbed.
- Bile provides another fraction of cholesterol.
- Intestinal secretions and turnover of the intestinal mucosal cells are other sources.
- Bile acids are detergents and are the most important factor affecting micelles formation.
- In the absence of bile acids, digestion and absorption of the cholesterol and triglyceride are severely affected.
- Most absorption of the cholesterol takes place in the jejunum and ileum.
- When cholesterol enters the intestinal cells, it is packaged with triglycerides, phospholipids, and apolipoprotein into large lipoprotein called chylomicrons.
- When there is an increased amount of fat in the diet, particularly triglycerides 98%, it will result in more micelles formation, allowing more cholesterol to be solubilized and absorbed.
- Approximately 60% of the total cholesterol in the male plasma is carried by the LDL 22%, HDL 13%, and Chylomicrons 5%.
- For food like egg yolk, meat, fat-diary products, and seafood, the average amount is 400 to 700 mg/day.
- The main source of cholesterol is diet. Another source is endogenous.
- Cholesterol esterification: Cholesterol, once formed, enters the blood circulation.
- It is then esterified and combine with apoprotein and apolipoprotein, and ultimately carried as a lipoprotein.
- Cholesterol esterification helps in the packing of the cholesterol into lipoproteins.
- Both dietary and synthesized cholesterol is converted to cholesteryl esters, which are easily packed into lipoproteins.
- Esterification increases the lipid carrying capacity of the lipoproteins in plasma and prevents the toxicity effect of the cholesterol.
- 75% bound to LDL.
- 25% bound to HDL.
- It is then esterified and combine with apoprotein and apolipoprotein, and ultimately carried as a lipoprotein.
- Biosynthesis of Cholesterol
- 90% of the cholesterol synthesis takes place in the liver and gut.
- Cholesterol synthesis takes place in three stages.
- The starting molecule is acetate.
- All body cells have the ability to synthesize cholesterol from Acetyl-CoA.
- Knowing the endogenous synthesis of the cholesterol, drugs are developed which lower the cholesterol level like mevastatin, lovastatin, simvastatin, pravastatin, and atorvastatin, which will suppress the HMG-CoA reductase.
- Cholesterol exists in two forms:
- Free cholesterol.
- Esterified cholesterol.
- 75% to 85% of the total cholesterol is in the form of esterified cholesterol.
- Cholesterol can be derived from a dietary source like meat, eggs, butter, and plants.
- 30 to 60% of the dietary cholesterol is absorbed.
- Once cholesterol is absorbed into the mucosal cells, it becomes part of the large micelle called Chylomicron.
- 75% to 85% of the total cholesterol is in the form of esterified cholesterol.
Cholesterol distribution in other lipids of the body:
Cholesterol found in: | % in other lipids |
Chylomicron | 2% |
VLDL | 5% to 8% |
LDL | 13% |
HDL | 6% |
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- Functions of cholesterol:
- Cholesterol is a blood lipid (fat).
- Cholesterol is a normal part of RBC.
- Cholesterol, when increased, leads to atherosclerosis and is the main lipid.
- Total raise level of cholesterol is associated with an increased risk of cardiovascular disease. Its subtypes LDL-C and HDL-C are more important than the total cholesterol.
- Functions of cholesterol:
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- Cholesterol is the basic unit of hormone produced by adrenal glands, ovaries, and testes.
- Cholesterol is needed for bile acids and cellular membranes.
- Cholesterol is transported in the circulation by carrier proteins.
- Cholesterol bound to high-density lipoprotein (HDL- cholesterol) is known as good cholesterol. This will prevent atherosclerosis.
- Cholesterol bound to low-density protein (LDL-cholesterol) is known as bad cholesterol and increases atherosclerosis chances.
- Also, the same is the cholesterol bound to very-low-density lipoprotein (VLDL) is bad.
- Increased Cholesterol level is associated with atherosclerosis and coronary vessel disease.
- Cholesterol functions:
- It is needed for the formation of steroids, sex hormones, and bile acids.
- This is the part of cellular membranes.
- It gives the risk of heart diseases.
Normal Cholesterol level
Source 1
Adult
- The desired level to prevent coronary disease is < 200 mg/dl
- Moderate risk is 200-239 mg/dl
- High risk is > 240 mg/dl
- CSF <0.5 mg/dl
Source 2
Sample | Male mg /dL | Female mg /dL |
Cord blood | 44 to 103 | 50 to 108 |
0 to 4 years | 114 to 203 | 112 to 200 |
5 to 9 years | 121 to 203 | 126 to 205 |
10 to 14 years | 119 to 202 | 124 to 201 |
20 to 24 years | 124 to 218 | 122 to 216 |
30 to 34 years | 138 to 254 | 130 to 230 |
40 to 44 years | 151 to 268 | 147 to 252 |
50 to 54 years | 158 to 277 | 162 to 285 |
60 to 64 years | 159 to 276 | 172 to 297 |
>70 years | 144 to 265 | 173 to 280 |
- To convert into SI unit x 0.0259 = mmol/L
Cholesterol and its relation to heart disease:
Children
- Desirable level is < 170 mg/dl
- Moderate risk is 170-199 mg/dl
- High risk is > 200 mg/dl
- Above 240 mg/dL = needs treatment.
- Nowadays cardiology association recommends the level to be around 160 mg/dl.
Cholesterol mg/dL | Risk |
<160 | Very low |
160 to 199 | low risk |
200 to 239 | moderate risk |
240 to 279 | high risk |
>280 | very high risk |
- According to the latest NHS research study, there is no relation between total cholesterol and heart disease risk.
ATP III (Adult treatment panel) recommendations for blood lipids are:
Chemical substance (Lipid) | Clinical effects on the people |
Cholesterol |
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HDL |
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LDL |
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ATP III (Adult treatment panel) LDL target level about the coronary vascular disease:
Risk factors | Details of risk factors | The target LDL level required ( This level is mandatory) |
Presence of coronary heart disease (CHD) or CHD-equivalent disease | CHD heart disease risk factors are:
|
<100 mg/dL |
2 or more major risk factors | Major risk factors including are:
|
<130 mg/dL |
<2 major risk factors | <160 mg/dL |
Framingham formula calculations (Risk score counting):
Risk factors | Points for the calculation for women | Points for the calculation for men |
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All non-smokers | 0 point | 0 point |
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10 years risk for cardiovascular diseases according to Framingham risks in %:
Total points | % Framingham score (risk) |
0 point | <1% |
1 to 4 points | 1% |
2 points | 5% to 6% |
7 points | 3% |
8 points | 4% |
9 points | 5% |
10 points | 6% |
11 points | 8% |
12 points | 10% |
13 points | 12% |
14 points | 16% |
15 points | 20% |
16 points | 25% |
17 points | >30% |
Total Cholesterol:
- Desirable level = <200 mg/dL
- Borderline level = 200 to 239 mg/dL
- High Risk level = >240 mg/dL
Increased Cholesterol (Hypercholesterolemia):
- Familial combined hyperlipidemia.
- Hyperlipoproteinemia type, 1V, V.
- Intra- and extrahepatic cholestasis.
- Glomerulonephritis.
- Nephrotic syndrome, and chronic renal failure.
- Malignant neoplasm of pancreas and prostate.
- Hypothyroidism.
- Gout.
- Diabetes mellitus.
- Alcoholism.
- Glycogen storage diseases type 1 (Von Gierke disease).
- Stress.
- Biliary cirrhosis.
Decrease Cholesterol (Hypocholesterolemia):
- alpha-Lipoprotein deficiency.
- Hepatocellular necrosis.
- Malignant neoplasm of the liver.
- Hyperthyroidism.
- Malabsorption and malnutrition.
- Severe acute illness.
- Extensive burns.
- Rheumatoid arthritis.
- Cholesterol-lowering medications.
Prevention, the recommendations, and treatment for the cholesterol level:
Total cholesterol <200 mg/dL | Check after 5 years |
Total cholesterol 200 to 239 mg/dL | 0 to 1 risk factor and no coronary disease. Needs diet control and repeat the test after one year. |
Total cholesterol >240 mg/dL | Diet control and/or drugs intervention |
Risk factors for heart diseases are:
- Cigarette smoking.
- Cerebrovascular disease.
- Diabetes mellitus.
- Hypertension.
- The family history of coronary heart disease.
- Sex as in male.
- Overweight >30%
- peripheral occlusive vascular disease.
Important:
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- There is variation in the level of cholesterol so take at least two samples.
- Critical value = >500 mg/dL.
Chemical substance Panic value (critical value) Cholesterol >240 mg/dL (>500 mg/dL) HDL-cholesterol <40 mg/dL LDL- cholesterol >160 mg/dL Triglycerides >500 mg/dL
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