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Estimating LDL-C in Patients With High Triglyceride Levels
Quick Takes
- LDL-C levels determined by the extended Martin/Hopkins equation were more accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations across all LDL-C classes in hypertriglyceridemia (triglyceride levels of 400-799 mg/dl).
- There was considerable underclassification of LDL-C at low levels across all methods, but particularly with the Friedewald and Sampson equations, raising concern for undertreatment.
- The AHA/ACC Cholesterol Guideline suggests that direct LDL-C assays or the Martin/Hopkins equation should be used over the Friedewald formula in patients with LDL-C <70 mg/dl and higher triglyceride levels.
Study Questions:
What is the accuracy of low-density lipoprotein cholesterol (LDL-C) estimation when comparing the Friedewald, extended Martin/Hopkins, and Sampson equations with LDL-C measured through ultracentrifugation at triglyceride levels of 400-799 mg/dl?
Methods:
The investigators conducted a cross-sectional study and evaluated consecutive patients at clinical sites across the United States with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006–December 31, 2015, with triglyceride levels of 400-799 mg/dl. Data analysis was performed from November 9, 2020–March 23, 2021. The main outcome measure was accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and direct LDL-C (dLDL-C) levels. Patients were randomly assigned 2:1 to derivation and validation data sets. Levels of dLDL-C were measured by vertical spin-density gradient ultracentrifugation. The LDL-C levels were estimated using the Friedewald method, with a fixed ratio of triglycerides to very low-density lipoprotein cholesterol (VLDL-C ratio of 5:1), extended Martin/Hopkins equation with a flexible ratio, and Sampson equation with VLDL-C estimation by multiple least-squares regression. The magnitude of error was calculated as estimated LDL-C minus dLDL-C and the percentages of patients with error levels of <5, 5-9, 10-19, 20-29, and ≥30 mg/dl were calculated for each LDL-C estimation method, stratified by guideline LDL-C category.
Results:
A total of 111,939 patients (mean [standard deviation] age, 52 [13] years; 65.0% male) with triglyceride levels of 400-799 mg/dl included, representing 2.2% of 5,081,680 patients in the database. Across all individual guideline LDL-C classes (<40, 40-69, 70-99, 100-129, 130-159, 160-189, and ≥190), estimation of LDL-C by the extended Martin/Hopkins equation was most accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations. In classifying LDL-C levels <70 mg/dl across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (67.3%) compared with Friedewald (5.1%) and Sampson (26.4%) equations. In addition, for classifying LDL-C levels <40 mg/dl across all triglyceride strata, the extended Martin/Hopkins equation was most accurate (57.2%) compared with the Friedewald (4.3%) and Sampson (14.4%) equations. However, considerable underclassification of LDL-C occurred. The magnitude of error between the Martin/Hopkins equation estimation and dLDL-C was also smaller: at LDL-C levels <40 mg/dl, 2.7% of patients had ≥30 mg/dl differences between dLDL-C and estimated LDL-C using the Martin/Hopkins equation compared with the Friedewald (92.5%) and Sampson (38.7%) equations.
Conclusions:
The authors concluded that the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400-799 mg/dl.
Perspective:
This study reports that LDL-C levels determined by the extended Martin/Hopkins equation were more accurate (62.1%) compared with the Friedewald (19.3%) and Sampson (40.4%) equations across all LDL-C classes in hypertriglyceridemia (triglyceride levels of 400-799 mg/dl). Furthermore, there was considerable underclassification of LDL-C at low levels across all methods, but particularly with the Friedewald and Sampson equations, raising concern for undertreatment. Overall, these findings provide insight into the extent of accuracy of LDL-C estimation across methods at high triglyceride levels. Of note, the 2018 American Heart Association/American College of Cardiology (AHA/ACC) Cholesterol Guideline suggests that direct LDL-C assays or the Martin/Hopkins equation should be used over the Friedewald formula in patients with LDL-C <70 mg/dl and higher triglyceride levels.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Hypertriglyceridemia, Lipid Metabolism, Nonstatins
Keywords: Cholesterol, Cholesterol, LDL, Cholesterol, VLDL, Diagnostic Imaging, Dyslipidemias, Hyperlipidemias, Hypertriglyceridemia, Metabolic Syndrome, Primary Prevention, Triglycerides, Treatment Outcome
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