The Friedewald Formula Underestimates LDL Cholesterol at low Concentrations

Abstract

Due to recent advances in the treatment of hypercholesterolemia, low density lipoprotein (LDL) cholesterol concentrations below 2.6 mmol/l have become attainable. In general, LDL cholesterol is determined indirectly according to Friedewald. We examined the performance of the Friedewald formula at low concentrations of LDL cholesterol in comparison with a beta-quantification method. We analyzed 176 samples from individuals treated by LDL apheresis with a mean LDL cholesterol concentration of 3.07 mmol/l and found that the Friedewald formula underestimated LDL cholesterol with a bias of -18.5%, -14.5%, -7.3%, and -3.8% at mean LDL cholesterol levels of 1.58, 2.4, 3.49, and 4.67 mmol/l, respectively. Thus, the lower the LDL cholesterol concentration was, the greater the negative bias. We conclude that the Friedewald formula may not be reliable at low LDL cholesterol concentrations produced by LDL apheresis. This finding may also be of relevance to the monitoring of patients being treated with lipid lowering drugs.

Comparison of equations for the calculation of LDL-cholesterol in hospitalized patients

“…The Friedewald formula was previously shown to incorrectly estimate LDL-C at the lowest TG levels [8,10] de Cordova (Wako) [33].…”

“…The formula requires fasting plasma high density lipoproteincholesterol (HDL-C), total cholesterol (TC), and TG, and is calculated as LDL-C = TC -HDL -(TG/5) for mg/dl (2.2 in mmol/l). This formula is less accurate in extremes of TG or TC values [7][8][9][10] or in patients with co-morbidities (eg. renal failure or diabetes) [2,11], but is widely used.…”

Low-Density Lipoprotein Cholesterol–Lowering Effects of AMG 145, a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia

“…Recent studies have shown that calculated LDL-C by Friedewald significantly underestimates LDL-C compared with the ultracentrifugation method in patients with very low LDL-C, 25,26 resulting in an overestimation of reduction when LDL-C falls below 1.8 mmol/L (70 mg/dL). In this study, reductions at 2 weeks using calculated LDL-C were in excess of 60% for both doses of AMG 145, and the reduction in the primary end point, LDL-C measured by ultracentrifugation, achieved with Q4W dosing of 420 mg AMG 145 was at least comparable with that achieved with Q2W dosing and better than that achieved with Q4W dosing of REGN727 in similarly statin-treated FH patients.…”

Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipoproteins and Vascular Diseases Division Working Group on Best Practices

“…It should not be used if patients are nonfasting, if triglycerides are Ͼ400 mg/dL (4.52 mmol/L), or if the patient has type III hyperlipoproteinemia. The equation is increasingly inaccurate with triglycerides Ͼ200 mg/dL (2.26 mmol/L) (81,82 ) and at relatively low LDL-C concentrations (83 ). The Friedewald formula is based on the measurement of total cholesterol, triglycerides, and HDL-C.…”