Laboratory Testing for Hyperlipidemia Management
The baseline lipid evaluation should include total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) calculated using the Friedewald formula, along with non-HDL-C and the TC/HDL-C ratio, obtained after a 12-hour fast when possible. 1
Core Lipid Panel Components
Primary Measurements
- Total cholesterol, triglycerides, HDL-C, and calculated LDL-C constitute the essential baseline evaluation for all patients with suspected or confirmed hyperlipidemia 1, 2
- LDL-C serves as both the primary screening parameter and the primary treatment target for cardiovascular risk reduction 1, 2
- Non-HDL-C (calculated as TC minus HDL-C) provides superior risk estimation in patients with hypertriglyceridemia, diabetes, metabolic syndrome, or chronic kidney disease 1, 2
LDL-C Calculation Method
- Use the Friedewald formula (LDL-C = TC - HDL-C - TG/5 in mg/dL, or TC - HDL-C - TG/2.2 in mmol/L) for calculating LDL-C when triglycerides are below 400 mg/dL (4.5 mmol/L) 1
- Direct LDL-C measurement is required when triglycerides exceed 400 mg/dL (4.5 mmol/L), as the Friedewald formula becomes unreliable at these levels 1
- The Friedewald formula cannot be used with non-fasting samples; in this situation, measure non-HDL-C instead 1
Fasting Requirements
When Fasting Is Essential
- A 12-hour fast is required primarily for accurate triglyceride measurement, which is the most variable lipid parameter 1
- Fasting samples are necessary when using the Friedewald formula to calculate LDL-C, particularly if baseline triglycerides are elevated 1
- Obtain a fasting lipid panel if initial non-fasting triglycerides are ≥400 mg/dL to accurately assess baseline LDL-C and triglyceride levels 3
When Non-Fasting Is Acceptable
- TC, HDL-C, apolipoprotein B (apo B), and apolipoprotein A1 (apo A1) can all be measured reliably in non-fasting samples 1, 3
- For screening programs using total cholesterol alone, fasting is not required 1
Advanced Lipid Testing
Apolipoprotein Measurements
- Apo B and the apo B/apo A1 ratio are at least as good as traditional lipid parameters for risk assessment and can be used as alternatives to LDL-C 1
- Measure apo B when cardiovascular risk remains uncertain after calculating 10-year ASCVD risk, particularly when triglycerides are ≥200 mg/dL where LDL-C calculations become unreliable 3
- Apo B ≥130 mg/dL constitutes a risk-enhancing factor corresponding to LDL-C ≥160 mg/dL and should favor more aggressive lipid-lowering therapy 3
- Apolipoprotein testing does not require fasting and remains accurate regardless of triglyceride levels 3
Lipoprotein(a) Testing
- Measure lipoprotein(a) [Lp(a)] once in a lifetime for risk stratification in patients with family history of premature ASCVD, personal history of unexplained ASCVD, or as part of comprehensive risk assessment 3
- Lp(a) ≥50 mg/dL or ≥125 nmol/L constitutes a risk-enhancing factor for cardiovascular disease 1, 3
- Lp(a) should be measured at least once in all patients at cardiovascular risk, including to explain poor response to statin treatment 4
Monitoring and Follow-Up Testing
Initial Assessment Timing
- Obtain a lipid profile at the time of diagnosis, at initial medical evaluation, and at least every 5 years in patients under age 40 years 1
- In younger patients with longer disease duration (such as youth-onset type 1 diabetes), more frequent lipid profiles may be reasonable 1
Treatment Monitoring
- Measure lipid panels 4-12 weeks after initiating statin therapy or any dose change to assess response and medication adherence 1, 2
- Annual lipid screening is recommended for adult diabetic patients once treatment goals are achieved 1, 2
- Reassess every 2 years if patients are at low-risk levels 2
Important Clinical Caveats
Intraindividual Variation
- Total cholesterol varies 5-10% and triglycerides vary ≥20% between measurements due to analytical variation, environmental factors (diet, physical activity), and seasonal variation 1
- Abnormal results should be confirmed by a repeated sample on a separate occasion, with the average of both results used for risk assessment 1
Special Populations Requiring Screening
- Screen all adults with cardiovascular risk factors, diabetes, metabolic syndrome, family history of premature CVD, or clinical signs such as xanthomas, xanthelasmas, or premature arcus cornealis 2
- Screen offspring of patients with severe dyslipidemia (familial hypercholesterolemia, familial combined hyperlipidemia, or chylomicronemia) 1
- Screen family members of patients with premature CVD 1
Laboratory Quality Considerations
- Use only certified and well-standardized laboratory methods whenever possible, as methodological developments may cause shifts in values, especially in patients with highly abnormal lipid levels 1
- Most commercially available methods for lipid analysis are well standardized, but reliability varies between laboratories for apolipoprotein measurements 3