Lipoprotein – Part 1 -High Density Lipoprotein (HDL), HDL-Cholesterol (HDL-C), Good Cholesterol

Sample

1. This test is done on the serum.
2. A fasting sample is preferred. Advised the patient to fast for 12 to 14 hours.
3. This test can be done on plasma as well.
4. Can store serum or plasma at 4 °C for 4 days (can keep for 5 to 7 days).

Precautions

1. Don’t use oxalate, fluoride, citrate, or heparin for the collection of the blood.
2. HDL values are age and sex-related.
3. HDL value is increased in Hypothyroidism and decreased in Hyperthyroidism.
4. Drugs that increase the value are oral contraceptives, aspirin, phenothiazine, steroids, and sulphonamides.
5. Smoking and alcohol decrease HDL value.

Purpose of the test (Indications)

1. Advised to evaluate coronary artery disease risk.
2. This can be advised as part of a lipid profile.

Pathophysiology

1. Lipoproteins are insoluble so these are transported in the plasma as a macromolecular complex.
   1. Lipoproteins are sphericle particle with:
      1. Nonpolar lipids are triglycerides and free cholesterol.
      2. Polar lipids are phospholipids and free cholesterol.

1. 1. 3. Lipoprotein is classified by electrophoresis on the basis of their physical and chemical structure as follows:
         1. Chylomicron. (These are primarily triglycerides).
         2. LDL. (Beta-lipoprotein These are primarily cholesterol).
         3. VLDL. (Pre-beta – lipoprotein These are mainly triglycerides).
         4. HDL. (Alpha – lipoprotein, These are mainly protein with the small amount of cholesterol)
      4. 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.

2. In the case of endogenous pathways, the lipoproteins are synthesized in the liver from carbohydrates and fats.

3. High-density lipoprotein cholesterol is produced by the liver and intestine.
   1. This can be separated by electrophoresis and ultracentrifugation.
   2. HDL composed of phospholipids and apolipoprotein (Apo A-1 and Apo – A-II), these are almost 90% of the total protein.
   3. The ratio of Apo – A-1 to Apo – A-11 is ∼ 3:1 by weight.
   4. The dominant Apoprotein is Apo-A I (67%) and it is followed by A-II, C, and E.
   5. This may be responsible for the transport of dietary cholesterol.
   6. HDL plays a role in the transportation of cholesterol to the liver from the tissue where it is excreted in the bile.
      1. HDL transports cholesterol to the liver where cholesterol serves as the precursor of the bile acids or part of the VLDL component.
      2. While lipoproteins transport cholesterol, triglycerides, and other insoluble fats.
4. HDL (Composition) consists of:
   1. Cholesterol 6%
   2. Cholesterol ester 13%
   3. Triglycerides 3%
   4. Phospholipids 28%
   5. Protein  50%
      1. HDL has very few triglycerides.
      2. There is a high percentage of proteins, phospholipids, and cholesterol.

5. The ratio of esterified and free cholesterol is 3:1.
6. The decreased level of HDL is atherogenic.
   1. HDL Raised level protects against atherosclerosis by removing the cholesterol from the arteries and taking it to the liver.
   2. HDL and LDL may combine to maintain cellular Cholesterol balance through the mechanism of LDL moving cholesterol into the arteries and HDL removing it from the arteries.
   3. HDL-C is good cholesterol and is proportional to coronary artery disease (CAD) risk.

7. When there is high cholesterol with a high level of HDL, the treatment is not indicated.
8. Functions of HDL:
   1. HDL is the carrier of cholesterol from the peripheral tissue.
   2. From peripheral tissue, HDL carries cholesterol to the liver for excretion in the bile known as reverse cholesterol transport.
   3. HDL has a protective role by preventing cellular uptake of cholesterol and lipids.
   4. HDL protects against cardiovascular diseases.

Table showing HDL and its relationship with coronary heart disease

Risk of heart disease	Male	Female
Low	60 mg/dL HDL	70 mg/dL HDL
Moderate	45 mg/dL HDL	55 mg/dL HDL
High	25 mg/dL HDL	35 mg/dL HDL

9. The total cholesterol / HDL-cholesterol ratio is very important to know the risk of coronary heart disease.
   1. A high ratio is associated with increased risk.
   2. The normal ratio should be at least 5:1 and the best is 3:1.

 Total cholesterol / HDL-cholesterol Ratio Risk for Coronary disease

Risk	Women	Men
Below average	3.3	3.4
Average	4.4	5.0
Above-average X 2 times	7.0	9.6
Above-average X 3 times	11.0	23.4

• HDL-cholesterol level of 70 mg/dl or greater is associated with longevity of life.

Normal

Source 1

HDL-Cholesterol

Age	Male mg/dL	Female mg/dL
Cord blood	6 to 53	13 to 56
5 to 9 year	38 to 75	36 to 73
10 to 14 year	37 to 74	37 to 70
15 to 19 year	30 to 63	35 to 74
20 to 24 year	30 to 63	33 to 79
25 to 29 year	31 to 63	37 to 83
30 to 34 year	28 to 63	36 to 77
35 to 39 year	29 to 62	34 to 82
40 to 44 year	27 to 67	34 to 88
45 to 49 year	30 to 64	34 to 87
50 to 54 year	28 to 63	37 to 92
55 to 59 year	28 to 71	37 to 91
60 to 64 year	30 to 74	38 to 92
65 to 69 year	30 to 75	35 to 96
>70 year	31 to 75	33 to 92

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

Source 2

HDL

• Male = >50 mg/dL
• Female = >55 mg/dL

Another source

HDL

• Men= 36 to 65 mg/dl or > 45 mg/dl (>0.75 mmol/L).
• Women= 35 to 80 mg/dl or > 55 mg/dl (>0.91 mmol/L).

Abnormal values of HDL:

1. <25 mg/dl             =  Coronary heart disease risk is 2 times and this is a dangerous level.
2. 26  to 35 mg/dl    =  The risk is 1.5 times. This is a high-risk group.
3. 36  to  44 mg/dl   = The risk is 1.2 times. This is a moderate risk group.
4. 45 to 59 mg/dl     = This is average-risk group.
5. Above 60 mg/dl  = Below average-risk group.
6. Critical values:
   1. Male = less than 35 mg/dl.
   2. Female = less than 40 mg/dl.

Increased HDL-C value seen in:

1. A chronic liver disease like cirrhosis, hepatitis, and alcoholism.
2. Long-term vigorous exercises.
3. Familial hyper- alpha-lipoproteinemia.
4. The increased level may be due to some drugs.
   1. Estrogen therapy.
   2. Moderate intake of alcohol.
   3. Insulin therapy.

Decreased HDL-C values seen in:

1. Poorly controlled diabetes
2. Cholestasis.
3. Chronic renal failure, uremia, and nephrotic syndrome.
4. Hypertriglyceridemia.
5. Familial hypo-alpha-lipoproteinemia.
6. alpha and beta – lipoproteinemia.
7. The decreased level may also be seen in some of the drugs.
   1. Steroids.
   2. Antihypertensive drugs.
   3. Diuretics.
   4. Beta-blockers.
   5. Thiazide.

Table showing the summary of 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 liver to adipose tissue

---