How to Calculate LDL Cholesterol
Use the Friedewald formula for routine clinical practice: LDL-C = Total Cholesterol - HDL-C - (Triglycerides/5) when measured in mg/dL, or LDL-C = Total Cholesterol - HDL-C - (Triglycerides/2.2) when measured in mmol/L. 1
The Standard Friedewald Formula
The European Society of Cardiology/European Atherosclerosis Society guidelines recommend the Friedewald formula as the baseline method for calculating LDL cholesterol from a standard lipid panel 1. This calculation requires three measurements:
- Total cholesterol (TC)
- HDL cholesterol (HDL-C)
- Triglycerides (TG)
In mg/dL: LDL-C = TC - HDL-C - (TG/5) 1, 2
In mmol/L: LDL-C = TC - HDL-C - (TG/2.2) 1, 2
The formula assumes a constant 5:1 ratio of triglycerides to cholesterol in VLDL particles 1.
Critical Limitations: When the Formula Fails
The Friedewald formula becomes invalid and should NOT be used when triglycerides exceed 400 mg/dL (4.5 mmol/L). 1, 2 At elevated triglyceride levels, the assumed VLDL composition changes significantly, making the calculation unreliable 1.
Additional limitations include:
- Do not use with non-fasting samples - The formula requires fasting lipid measurements because postprandial triglycerides invalidate the calculation 1
- Accuracy decreases at very low LDL-C levels - When LDL-C is below 70 mg/dL (1.8 mmol/L), the Friedewald formula becomes increasingly inaccurate 1, 3
- Methodological errors accumulate - Since three separate measurements are required, analytical variation from each test compounds the final error 1
Alternative Approaches When Friedewald Fails
For High Triglycerides (>400 mg/dL or >4.5 mmol/L):
Use direct LDL-C measurement or calculate non-HDL-C instead. 1, 2 Non-HDL-C is simply: Total Cholesterol - HDL-C, and this provides a reliable alternative target when triglycerides are elevated 1.
For Very Low LDL-C (<70 mg/dL or <1.8 mmol/L):
Consider direct LDL-C measurement or modified calculation methods to improve accuracy. 1 The American College of Cardiology notes that direct measurements can differ by approximately 15% from calculated values at these low levels 1, 2.
Newer equations like the Sampson-NIH2 formula are valid up to triglycerides of 800 mg/dL (9 mmol/L) and provide better accuracy than Friedewald, particularly in patients with hypertriglyceridemia or low LDL-C 4, 5.
Practical Clinical Algorithm
Step 1: Obtain a fasting lipid panel measuring total cholesterol, HDL-C, and triglycerides 1
Step 2: Check triglyceride level:
- If TG <400 mg/dL (<4.5 mmol/L): Use Friedewald formula 1, 2
- If TG ≥400 mg/dL (≥4.5 mmol/L): Use direct LDL-C measurement or non-HDL-C 1, 2
Step 3: If calculated LDL-C is <70 mg/dL (<1.8 mmol/L), consider confirming with direct measurement for treatment decisions 1, 3
Common Pitfalls to Avoid
Never use the Friedewald formula on non-fasting samples - triglyceride levels will be falsely elevated, leading to underestimation of LDL-C by 4-6 mg/dL or more 1. If only non-fasting samples are available, use non-HDL-C instead 1.
Do not report calculated LDL-C values below 30 mg/dL (0.8 mmol/L) - these have significant deviation from actual measured values and should not guide treatment decisions 3.
Remember that lipid-lowering medications alter the mathematical relationships between lipid components, potentially making calculated LDL-C less accurate in patients already on statin therapy 2.