Lipid and lipoprotein concentrations vary during the normal course of daily activity. Studies have demonstrated that within person variability is sufficient to make an individual move in and out of the predefined risk categories defined by the National Cholesterol Education Program (NCEP). As many as 11% of patients would be mistreated if risk assessment were made on the basis of a single lipid panel. NCEP guidelines acknowledge this variation by stressing that patient management decisions should be based on an average of at least two results. The extent of within person biological variability (expressed as the coefficient of variation) for each lipid fraction is summarized in the following table.
Interval |
Total-C |
HDL-C |
LDL-C |
TG |
Day |
2.5% |
4.5% |
7.8% |
36% |
Month |
4.8% |
7.7% |
9.6% |
24% |
Year |
6.1% |
8.4% |
13.6% |
26% |
Triglycerides fluctuate widely, even during a single day, because they exhibit diurnal variation. Triglyceride concentration is lowest at 3 a.m., rises until mid-afternoon and decreases thereafter. Cholesterol and LDL cholesterol are not subject to diurnal variation, but are affected by seasonal variation. Levels increase as much as 5% in winter. Other sources of intra-individual variation are listed below.
Variable |
Effect |
Menstruation |
6-9% TC increase in follicular phase |
Pregnancy |
30% TC & 200% TG increase at term |
Acute illness |
15% TC & 25% HDL decrease |
Weight loss |
10% TC, 10% HDL, 40% TG decrease |
Exercise |
3-7% TC decrease & 3-10% HDL increase |
Smoking |
3% TC & 9% TG increase, 6-11% HDL decrease |
Posture |
10-20% higher standing than lying |
Specimen handling |
Stable for 3 days |
Besides biological variation, lipid values are also dependent on the laboratory's analytical performance. Today's chemistry analyzers are very precise; analytical variation in reputable laboratories is less than one half of biological variation. The coefficient of variation at Saint Luke's Hospital Laboratory is 2.2% for cholesterol, 3.8% for HDL cholesterol and 4.2% for triglycerides. Combining biological and analytical variability, it is possible to calculate the magnitude of change that must occur to have 95% confidence that a change in lipid value is medically significant.
Lipid |
Result (mg/dL) |
Significant Change |
Cholesterol |
180 |
32 |
| |
200 |
35 |
| |
220 |
39 |
| |
240 |
43 |
| |
260 |
46 |
| |
280 |
50 |
| |
300 |
53 |
HDL |
25 |
7 |
| |
30 |
8 |
| |
35 |
10 |
| |
40 |
11 |
| |
45 |
12 |
| |
50 |
14 |
| |
55 |
15 |
| |
60 |
16 |
| |
65 |
18 |
Triglycerides |
100 |
84 |
| |
150 |
126 |
| |
200 |
168 |
| |
250 |
210 |
| |
300 |
252 |
| |
350 |
293 |
| |
400 |
336 |
| |
450 |
378 |
| |
500 |
420 |
Cholesterol concentration must change at least 18%, HDL cholesterol 27% and triglycerides 84% before one can be assured that the difference is not simply due to intra-individual and analytical changes.
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