Despite the negative connotation of LDL in cardiovascular disease, it is a very important cellular metabolite and precursor for adrenocortical cells, lymphocytes, and renal cells. The liver uses LDL for synthesis of bile acids and free cholesterol, which is secreted into the bile. In the normal human, 70% to 80% of LDL is removed from the plasma each day and secreted in the bile by utilization of the LDL receptor pathway.
The final metabolic pathway is the transformation of HDL cholesterol in extrahepatic tissue. HDL cholesterol carries the plasma enzyme lecithin cholesterol acyltransferase (LCAT). LCAT allows HDL cholesterol to resynthesize lipids to VLDL cholesterol and recycle the lipid cascade. HDL cholesterol acts as a “scavenger” and therefore reverses the deposit of cholesterol into tissues. There is good evidence that HDL cholesterol is responsible for the reversal of atherosclerotic changes in vessels, hence the term “good cholesterol” (27).
Hyperlipoproteinemia When cholesterol is measured, various fractions are reported. Plasma cholesterol or total cholesterol consists of cholesterol and unesterified cholesterol fractions. If triglycerides are analyzed in conjunction with cholesterol, then assumptions can be made concerning which metabolic pathway may be abnormal. Elevation of both total cholesterol and triglycerides signifies a problem with chylomicrons and VLDL synthesis. If the triglyceride-to-cholesterol ratio is greater than 5:1, the predominant fractions are chylomicrons and VLDL. A triglycerides-to-cholesterol ratio less than 5:1 signifies a problem in the VLDL and LDL fractions.
Hyperlipoproteinemias are defined by establishing a “normal population” and then setting various limits at the 10th and 90th percentiles. Standards for women set the 80th percentile for cholesterol at 240 mg/dL and the 50th percentile at 200 mg/dL (Table 9.8). A diet low in animal fat and high in vegetable and fiber consumption helps control the level of cholesterol (27–29). Plasma elevations of chylomicrons, LDL, VLDL, various remnants of IDL, and VLDL are classified by the elevated fraction.
Table 9.8 Initial Classification Based on the Total Cholesterol, LDL, HDL, and Triglyceride Levels
LDL, low-density lipoprotein; HDL, high density lipoprotein. Adapted from Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486–2497.
There are multiple causes of variation in cholesterol measurements (30,31). Major sources of variation within individuals include diet, obesity, smoking, ethanol intake, and the effects of exercise. Other clinical conditions that affect cholesterol measurements include hypothyroidism, diabetes, acute or recent myocardial infarction, and recent weight changes. Measurements can be altered by fasting, position of the patient while the sample is drawn, the use and duration of venous occlusion, various anticoagulants, and the storage and shipping conditions.
Intrapersonal variation is well described. If multiple samples are taken within a given day, weekly and monthly variations can be as high as 6%. At least two specimens should be taken 1 month apart and should be collected in the same dietary state in order for a lipid value to be considered accurate.