Lipid Testing for Cholesterol Evaluation
For cholesterol screening, measure total cholesterol and HDL cholesterol as the initial test, which can be done in a non-fasting state; if triglycerides are ≥400 mg/dL or if the patient has elevated cardiovascular risk, obtain a fasting lipid panel that includes LDL cholesterol calculation. 1
Core Testing Components
The standard lipid panel should include:
- Total cholesterol
- HDL cholesterol (high-density lipoprotein)
- LDL cholesterol (low-density lipoprotein) - calculated or directly measured
- Triglycerides
- Non-HDL cholesterol (calculated as total cholesterol minus HDL)
Fasting vs. Non-Fasting
Non-fasting samples are acceptable for initial screening and most clinical decisions 2. Total cholesterol and HDL cholesterol levels are minimally affected by recent food intake and provide adequate information for risk assessment.
Fasting samples are required when:
- Initial non-fasting triglycerides are ≥400 mg/dL (≥4.5 mmol/L) 1
- Accurate LDL cholesterol calculation is needed (the Friedewald formula requires fasting)
- Evaluating hypertriglyceridemia specifically
Special Considerations for LDL Cholesterol Measurement
For patients with LDL cholesterol <70 mg/dL (<1.8 mmol/L), direct LDL cholesterol measurement or modified LDL cholesterol estimates are reasonable to improve accuracy over the standard Friedewald formula 1. The Friedewald formula becomes less reliable at very low LDL levels and when triglycerides are elevated.
Confirmation Testing
Abnormal results should be confirmed with a repeat sample on a separate occasion, and the average of both results should be used for risk assessment and treatment decisions 2. This reduces the impact of biological and analytical variability.
Who Should Be Screened
Universal Screening:
- All adults ≥20 years of age should undergo lipid screening 1
- Men ≥35 years and women ≥45 years should be routinely screened 2
High-Risk Younger Adults (Men 20-35, Women 20-45):
Screen if any of the following risk factors are present 2:
- Diabetes mellitus
- Family history of cardiovascular disease before age 50 in male relatives or age 60 in female relatives
- Family history suggestive of familial hyperlipidemia
- Multiple coronary heart disease risk factors (tobacco use, hypertension)
Screening Intervals
Every 5 years is a reasonable interval for most adults 2. However:
- Shorter intervals for persons with lipid levels approaching treatment thresholds
- Longer intervals for low-risk persons with repeatedly normal measurements
Additional Testing Considerations
Lipoprotein(a) measurement should be performed once in adults to identify those with very high inherited lipoprotein(a) levels, as this represents a genetic risk factor that persists throughout life 3.
Apolipoprotein B is not routinely required for initial screening but may provide additional risk stratification in specific cases, particularly when triglycerides are elevated 4.
Common Pitfalls to Avoid
- Do not rely on total cholesterol alone - HDL cholesterol measurement significantly improves cardiovascular risk identification 2
- Do not use HDL ratios (total cholesterol/HDL) as obsolete measures - focus on absolute LDL cholesterol targets based on cardiovascular risk 5
- Do not routinely measure triglycerides for screening unless there are specific indications, as evidence for triglycerides as an independent risk factor remains conflicting 2
- Do not assume fasting is always necessary - this outdated requirement delays testing and reduces screening rates without improving most clinical decisions
Primary Treatment Target
LDL cholesterol is the primary target for treatment decisions and monitoring 1, 5. Non-HDL cholesterol (which captures all atherogenic lipoproteins) serves as a useful secondary target, particularly in patients with elevated triglycerides.