Why Does Your LDL Cholesterol Depend on the Equation?

Most labs don’t measure LDL cholesterol. They calculate it from your total cholesterol, HDL cholesterol, and triglycerides, using one of several equations. When your triglycerides are normal, the equations agree closely. When triglycerides are high, or LDL is very low, they can differ by enough to change a treatment decision, which is why it matters which one your lab used.

This article is general information, not medical advice.

The Equations

• Friedewald (1972). LDL = total cholesterol − HDL − triglycerides ÷ 5 (in mg/dL). It assumes a fixed ratio of triglycerides to the cholesterol carried in very-low-density lipoprotein (VLDL), which holds poorly when triglycerides are high. It isn’t used above 400 mg/dL (4.5 mmol/L) of triglycerides.
• Martin-Hopkins (2013). Uses a different divisor for each combination of triglycerides and non-HDL cholesterol, from a table built from 1.3 million lipid profiles. Martin and colleagues found it classified LDL correctly more often than Friedewald, especially when LDL was under 70 mg/dL and triglycerides were raised.
• NIH equation (Sampson, 2020). A formula developed at the US National Institutes of Health that stays accurate for triglycerides up to 800 mg/dL (9 mmol/L).

Direct LDL

A direct LDL test measures LDL cholesterol chemically rather than calculating it. It’s used when triglycerides are too high for the equations, or when a lab chooses to. Direct assays from different manufacturers don’t always agree, so they’re not automatically more accurate than a good equation.

Why It Matters

Friedewald tends to underestimate LDL when triglycerides are high and LDL is low: just the situation of someone on a statin with high triglycerides. An LDL that reads as on-target by one equation may be above target by another. If your triglycerides are high, ask which equation your lab uses, or consider non-HDL cholesterol or apolipoprotein B, which don’t depend on an equation; see What Is ApoB, and Is It Better Than LDL Cholesterol?

Compare LDL values over time only when they were worked out the same way.

Following It in Kaizora

Kaizora keeps LDL Cholesterol (Direct), LDL Cholesterol (Friedewald), LDL Cholesterol (Martin-Hopkins), and LDL Cholesterol (NIH Equation) as four separate metrics on Labs, so a change of method never looks like a change in you. Log each result as your lab reported it, with the laboratory and the range it printed; your report usually says the method. A draw’s results share their time and laboratory, so your triglycerides sit beside the LDL they were used to calculate.

The Short Version

• Most LDL results are calculated, by Friedewald, Martin-Hopkins, or the NIH equation.
• They agree when triglycerides are normal, and diverge when triglycerides are high or LDL is low.
• Friedewald can underestimate LDL then; compare values only from the same method.

Sources

• Friedewald WT, Levy RI, Fredrickson DS, “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge,” Clinical Chemistry 18, no. 6 (1972): 499–502. doi:10.1093/clinchem/18.6.499
• Martin SS et al., “Comparison of a novel method vs the Friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile,” JAMA 310, no. 19 (2013): 2061. doi:10.1001/jama.2013.280532
• Sampson M et al., “A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia,” JAMA Cardiology 5, no. 5 (2020): 540. doi:10.1001/jamacardio.2020.0013