What is the difference between fasting and non-fasting (without fasting) cholesterol testing?

Fasting vs Non-Fasting Cholesterol Testing

Non-fasting lipid profiles are now the recommended standard for routine cholesterol screening and cardiovascular risk assessment in most clinical situations, as they are equally predictive of cardiovascular outcomes, more convenient for patients, and only show minimal differences from fasting values. 1

Key Differences Between Fasting and Non-Fasting Samples

Lipid Value Changes

The actual differences between fasting and non-fasting measurements are clinically insignificant for most lipid parameters 2, 3:

• Triglycerides: Increase by maximum mean of +26 mg/dL (+0.3 mmol/L) 2, 3
• Total cholesterol: Decrease by -8 mg/dL (-0.2 mmol/L) 2, 3
• LDL cholesterol: Decrease by -8 mg/dL (-0.2 mmol/L) 2, 3
• HDL cholesterol: Minimal change of -8 mg/dL (-0.1 mmol/L) 2, 3
• Non-HDL cholesterol: Decrease by -8 mg/dL (-0.2 mmol/L) 2
• Apolipoprotein B, Apolipoprotein A1, and Lipoprotein(a): Essentially unchanged 2, 3

Prognostic Value

Non-fasting triglycerides are actually superior predictors of cardiovascular disease risk compared to fasting levels, as the non-fasting state represents the majority of a 24-hour cycle and better captures atherogenic lipoprotein levels 1, 4. The postprandial state enriched in dietary fat may affect hepatic removal of circulating remnants, permitting their uptake by macrophages 1.

When to Use Non-Fasting vs Fasting Samples

Use Non-Fasting Samples (Preferred) 1:

• Routine screening for cardiovascular risk assessment in adults ≥20 years 1
• Baseline lipid assessment before initiating statin therapy in primary or secondary prevention 1
• Children and adolescents with family history of early CVD or hypercholesterolemia 1
• Most clinical scenarios where convenience and patient compliance are priorities 3

Use Fasting Samples (Specific Situations) 1:

• When non-fasting triglycerides ≥400 mg/dL (≥4.5 mmol/L): Repeat with fasting sample to assess accurate triglyceride levels and calculate LDL-C 1, 3
• Family history of premature ASCVD or genetic hyperlipidemia: Fasting profile reasonable for initial evaluation to identify familial lipid disorders 1, 5
• **When LDL-C <70 mg/dL (<1.8 mmol/L)**: The Friedewald formula becomes unreliable at very low LDL-C levels, particularly when triglycerides >150 mg/dL 1
• Suspected severe hypertriglyceridemia: When more precision is needed for triglyceride assessment 1

Clinical Implementation Algorithm

Step 1: Initial Screening

• Order non-fasting lipid profile for routine cardiovascular risk assessment 1
• Measure: total cholesterol, triglycerides, HDL-C, and calculate LDL-C 1

Step 2: Interpret Results

• If triglycerides <400 mg/dL: Use non-fasting values for risk assessment and treatment decisions 1
• If triglycerides ≥400 mg/dL: Order fasting lipid profile for accurate assessment 1

Step 3: Special Populations

• Children (ages 2-21): Non-fasting total cholesterol acceptable for screening; fasting profile if family history of premature CVD or if initial total cholesterol >170 mg/dL 1
• Suspected familial hypercholesterolemia: Consider fasting profile initially, though non-fasting acceptable with caution regarding Friedewald calculation 5

Important Caveats and Pitfalls

Friedewald Formula Limitations 1:

• Cannot be used when triglycerides ≥400 mg/dL (≥4.5 mmol/L) 1
• Unreliable at LDL-C <70 mg/dL, particularly with triglycerides >150 mg/dL 1
• Should not be used with non-fasting samples when triglycerides are elevated 1
• Consider direct LDL-C measurement or modified LDL-C estimate when Friedewald is unreliable 1

Technical Considerations 1:

• Postural effects: Triglycerides reduced by 12% after 20-30 minutes of sitting/lying, 15-20% by 40 minutes 1
• Standardize blood sampling: Patient should sit for 5 minutes before phlebotomy 1
• Tourniquet time: Should not be applied >1 minute before blood withdrawal to avoid 10-15% triglyceride elevation 1
• Serum vs plasma: Plasma tubes reduce triglycerides by 3% compared to serum; use consistently 1

Biological Variability 1:

• Triglycerides have median variation of 23.5% (much higher than total cholesterol at 4.9%, HDL-C at 6.9%, or LDL-C at 6.5%) 1
• Confirm abnormal results with repeat measurement on separate occasion 6

Laboratory Reporting 3:

For non-fasting samples, flag abnormal concentrations as:

• Triglycerides ≥175 mg/dL (≥2 mmol/L) 3
• Total cholesterol ≥190 mg/dL (≥5 mmol/L) 3
• LDL cholesterol ≥115 mg/dL (≥3 mmol/L) 3
• Non-HDL cholesterol ≥150 mg/dL (≥3.9 mmol/L) 3

Advantages of Non-Fasting Approach 4, 3:

• Patient convenience: No need to fast or schedule early morning appointments 4, 3
• Improved compliance: Easier for patients to complete testing 3
• Safety: Minimizes hypoglycemia risk in diabetic patients 4
• Laboratory efficiency: Simplifies blood sampling workflow 4, 3
• Real-world representation: Better reflects typical atherogenic lipoprotein exposure throughout the day 1, 2