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High Density Lipoprotein Cholesterol

Numerous epidemiological and interventional studies have documented that HDL cholesterol (HDL-C) is a major independent risk factor for coronary heart disease (CHD). Each 1 mg/dL increase in HDL-C results in a 2% decrease in CHD in men and a 3% decrease in women. The relative risk of CHD is 1.00 at a HDL-C level of 45 mg/dL in men and 55 mg/dL in women.

HDL Cholesterol Level & Relative Risk of CAD

HDL Cholesterol (mg/dL)

Men

Women

30

1.82

-

35

1.49

-

40

1.22

1.94

45

1.00

1.55

50

0.82

1.25

55

0.67

1.00

60

0.55

0.80

65

0.45

0.64

70

-

0.52

The ratio of total cholesterol to HDL-C is believed to be a more sensitive indicator of CHD than HDL-C alone. Relative risk of CHD is greatest when total cholesterol is high and HDL-C is low.

Total Cholesterol (mg/dL)

HDL-C

185

200

210

220

225

244

260

300

25

1.34

1.50

1.60

1.80

2.00

3.00

4.00

6.00

30

1.22

1.37

1.46

1.64

1.82

2.73

3.64

5.46

35

1.00

1.12

1.19

1.34

1.49

2.24

2.98

4.47

40

0.82

0.92

0.98

1.10

1.22

1.83

2.44

3.66

45

0.67

0.75

0.80

0.90

1.00

1.50

2.00

3.00

50

0.55

0.62

0.66

0.74

0.82

1.23

1.64

2.46

55

0.45

0.50

0.54

0.60

0.67

1.01

1.34

2.01

60

0.37

0.41

0.44

0.50

0.55

0.83

1.10

1.65

65

0.30

0.34

0.36

0.41

0.45

0.68

0.90

1.35

Approximately 11% of adult men have isolated low concentrations of HDL cholesterol. The prevalence is higher, 17 to 36%, in populations with coronary artery disease. In May 2001 the National Cholesterol Education Program Adult Treatment Panel III changed the definition of low HDL-C from <35 to < 40 mg/dL.

Before initiating a treatment plan for low HDL-C, secondary conditions that spuriously depress HDL-C need to be ruled out. The most common secondary causes of altered lipids include hypothyroidism, diabetes mellitus, uremia, and liver disease. Low HDL-C is often combined with high triglycerides. Many of these patients have the metabolic syndrome, which is attributed to insulin resistance. This syndrome is characterized by abdominal obesity, atherogenic dsylipidemia (elevated triglycerides, small LDL particles, low HDL cholesterol), raised blood pressure, and insulin resistance with or without glucose intolerance.

Acute illnesses such as myocardial infarction, surgical procedures, viral illnesses or any inflammatory condition decrease total cholesterol, LDL-C and HDL-C and increase triglycerides. HDL-C is decreased 12% to 32% within two to five days after a myocardial infarction. This depression may last up to 30 days. Ideally, lipid measurements should not be performed within 60 days of a myocardial infarction or major surgical procedure.

Some commonly prescribed drugs may lower HDL-C levels including diuretics, progestins, androgens, prednisolone, probucol and beta-adrenergic blockers. Estrogen replacement therapy and phenytoin have the opposite effect of raising HDL-C concentration. Moderate alcohol use also increases HDL-C levels. Men who consume one drink or less per day do not experience a significant increase in HDL-C, but women do.

Low HDL-C concentration is also associated with cigarette smoking, low levels of physical activity, being overweight and a high carbohydrate (>60% of calories) diet. Cigarette smoking has a dose dependent negative effect, but generally causes a 5 to 9 mg/dL decrease in HDL-C. Exercise in sedentary men increases HDL-C, but there is a threshold effect. Moderate exercise is needed to significantly increase HDL-C; joggers running 35 miles per week for 10 months experience a 10% increase in HDL-C. Some of this beneficial effect may actually be due to weight loss. Weight loss in obese adults raises HDL-C approximately 0.8 mg/dL for every unit decrease in body mass index.

Approximately 0.25% of the population has elevated HDL-C levels >100 mg/dL. A few mutations produce very high HDL levels, but in everyday practice high HDL-C occurs more frequently than can be accounted for by these rare mutations. Exercise and dieting seldom increase HDL-C above 100 mg/dL. A few common factors have been found including female gender, estrogen therapy, excessive alcohol intake, H2 blocker medications, and primary biliary cirrhosis. Many of these patients have a positive history for CAD. A very high HDL cholesterol level is not always synonymous with the absence of CAD and increased life expectancy.

See Lipid Panel for diagnostic and treatment algorithms.

Reference range is > 40 mg/dL.

Specimen requirement is one SST tube of blood drawn after an overnight fast.

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