Preventive Cardiology, Clinical Lipidology & Laboratory Diagnostics
Martin-Hopkins Adjustable LDL-C vs Friedewald Bias Formula
Calculate Atherogenic Non-HDL Cholesterol (TC - HDL), Legacy Fixed-Divisor Friedewald LDL-C (TC - HDL - TG/5), ACC/AHA Guideline Martin-Hopkins Adjustable-Divisor LDL-C (TC - HDL - TG/f_MH), and Friedewald Underestimation Gap.
Catch dangerous Friedewald LDL-C underestimation in elevated triglycerides and PCSK9/statin therapy!
For half a century, clinical labs estimated LDL Cholesterol via Friedewald’s 1972 equation LDL_F = Total_Cholesterol - HDL_C - (Triglycerides / 5), assuming a fixed 5:1 mass ratio of triglycerides to VLDL cholesterol! Yet in patients with metabolic syndrome / hypertriglyceridemia (TG = 200–399 mg/dL) and aggressive statin/PCSK9 therapy targeting LDL-C < 70 mg/dL, VLDL particles carry MORE triglyceride per cholesterol molecule (true TG:VLDL-C ratio f_MH = 6.5 to 11.9!), causing TG / 5 to OVERESTIMATE VLDL-C and falsely UNDERESTIMATE atherogenic LDL-C by 10–25 mg/dL! ACC/AHA Cholesterol Guidelines therefore endorse the Martin-Hopkins equation LDL_MH = TC - HDL_C - (TG / f_MH) alongside Atherogenic Non-HDL-C = TC - HDL_C!
Verify on a Secondary-Prevention Coronary Patient—Total_Cholesterol = 165 mg/dL (B2), HDL_Cholesterol = 40 mg/dL (B3 -> Non-HDL Cholesterol = 125.00 mg/dL in E2), Fasting_Triglycerides = 272 mg/dL (B4), and Stratum-Matched Martin-Hopkins Divisor f_MH = 6.8 (B5): Legacy Friedewald reports 165 - 40 - (272 / 5) = 70.60 mg/dL (borderline "at goal" in E3!), whereas Martin-Hopkins reveals true LDL-C = 165 - 40 - (272 / 6.8) = 125 - 40 = 85.00 mg/dL (E4)—exposing a +14.40 mg/dL Friedewald Underestimation Error (E5) that warrants lipid-lowering intensification!
| Clinical Lipid Panel Metric (TC=165, HDL=40, TG=272 mg/dL, f_MH=6.8) | Formula | Verified Output |
|---|---|---|
| Atherogenic Non-HDL-C (mg/dL) | Total_Cholesterol - HDL_C | 125.00 mg/dL |
| Legacy Friedewald LDL-C (mg/dL) | TC - HDL_C - (Triglycerides / 5) | 70.60 mg/dL (105.00 @ TG=100) |
| Martin-Hopkins LDL-C (mg/dL) | TC - HDL_C - (Triglycerides / f_MH) | 85.00 mg/dL (105.00 @ TG=100, f=5) |
| Friedewald Underestimation Gap | Martin_Hopkins_LDL - Friedewald_LDL | +14.40 mg/dL (0.00 @ f_MH=5.0) |
Martin-Hopkins Adjustable-Divisor LDL Cholesterol Formula
Validate TC > HDL > 0, Triglycerides in (0, 800) mg/dL, Martin-Hopkins divisor f_MH in [3.1, 12.0], and positive estimated LDL-C!
=LET(tc_m, B2, hd_m, B3, tg_m, B4, mh_f, B5, IF(OR(tc_m <= 0, hd_m <= 0, tc_m <= hd_m, tg_m <= 0, tg_m >= 800, mh_f < 3.1, mh_f > 12, (tc_m - hd_m - tg_m / mh_f) <= 0), "Invalid Lipid Panel Input", ROUND(tc_m - hd_m - (tg_m / mh_f), 2)))Normotriglyceridemic Concordance Check (Set TG = 100 mg/dL, f_MH = 5.0)
Test a normal fasting lipid profile with B4 = 100 mg/dL and B5 = 5.0: Friedewald E3 and Martin-Hopkins E4 both equal 105.00 mg/dL with 0.00 mg/dL discordance in E5!
=IF(ISTEXT(E4), E4, ROUND(E4 - E3, 2))Try the example
Use the original values or change them to test your understanding.