• To estimate Low-Density Lipoprotein (LDL) cholesterol when a direct LDL measurement is not available (which is the standard in most clinical laboratories).

LDL = Total Cholesterol - HDL - Very Low Density Lipoprotein (VLDL). Since VLDL is difficult to measure directly, it is estimated as Triglycerides / 5 (if using mg/dL) or Triglycerides / 2.2 (if using mmol/L).

• The absolute ratio of TG to VLDL-C is rarely exactly 5. It varies across the spectrum of triglyceride and cholesterol levels.
• When triglycerides are high (e.g., 200-399 mg/dL) or LDL is very low (<70 mg/dL), the Friedewald equation systematically underestimates true LDL levels.
• This underestimation can falsely reassure clinicians and lead to undertreatment of high-risk patients.

In patients with hypertriglyceridemia, diabetes, or metabolic syndrome, calculating Non-HDL Cholesterol (Total Cholesterol - HDL) is often a better predictor of cardiovascular risk than estimated LDL, as it accounts for all atherogenic apolipoprotein B-containing lipoproteins.