TY - JOUR
T1 - Comparison of Methods to Estimate Low-Density Lipoprotein Cholesterol in Patients with High Triglyceride Levels
AU - Sajja, Aparna
AU - Park, Jihwan
AU - Sathiyakumar, Vasanth
AU - Varghese, Bibin
AU - Pallazola, Vincent A.
AU - Marvel, Francoise A.
AU - Kulkarni, Krishnaji
AU - Muthukumar, Alagarraju
AU - Joshi, Parag H.
AU - Gianos, Eugenia
AU - Hirsh, Benjamin
AU - Mintz, Guy
AU - Goldberg, Anne
AU - Morris, Pamela B.
AU - Sharma, Garima
AU - Blumenthal, Roger S.
AU - Michos, Erin D.
AU - Post, Wendy S.
AU - Elshazly, Mohamed B.
AU - Jones, Steven R.
AU - Martin, Seth S.
N1 - Funding Information:
Administrative, technical, or material support: Varghese, Kulkarni, Gianos, Jones, Martin. Supervision: Varghese, Pallazola, Marvel, Sharma, Blumenthal, Jones, Martin. Conflict of Interest Disclosures: Dr Muthukumar reported receiving grants from Roche Diagnostics and nonfinancial support from Abbott Diagnostics outside the submitted work. Dr Joshi reported receiving grants from the American Heart Association, National Aeronautics and Space Administration, Novo Nordisk, Sanofi, AstraZeneca, GlaxoSmithKline, Novartis, and Amgen; personal fees from Bayer; and equity from G3 Therapeutics outside the submitted work. Dr Hirsh reported receiving consulting fees from Regeneron Advisory Board outside the submitted work. Dr Mintz reported receiving honoraria from Esperion Honorarium and Janssen outside the submitted work. Dr Goldberg reported receiving honoraria from the National Lipid Association outside the submitted work. Dr Morris reported receiving consulting fees from Amgen, Modest, Esperion, and Pfizer outside the submitted work. Dr Michos reported receiving consulting fees from Esperion, AstraZeneca, Amarin, and Novartis outside the submitted work. Dr Martin reported receiving grants from the David and June Trone Family Foundation during the conduct of the study and grants from the American Heart Association, Patient-Centered Outcomes Research Institute, National Institutes of Health, and Pollin Digital Innovation Fund; and consulting fees from AstraZeneca, Amgen, Esperion, Kaneka, Sanofi, 89bio, and DalCor Pharmaceuticals outside the submitted work; in addition, Dr Martin has a patent for System of LDL-C calculation pending filed by Johns Hopkins University. No other disclosures were reported.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
PY - 2021/10/28
Y1 - 2021/10/28
N2 - Importance: Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited. Objective: To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations. Design, Setting, and Participants: This cross-sectional study evaluated consecutive patients at clinical sites across the US with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006, to December 31, 2015, with triglyceride levels of 400 to 799 mg/dL. Data analysis was performed from November 9, 2020, to March 23, 2021. Main Outcomes and Measures: Accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and 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. Results: A total of 111939 patients (mean [SD] age, 52 [13] years; 65.0% male) with triglyceride levels of 400 to 799 mg/dL were included, representing 2.2% of 5081680 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 less than 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 less than 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 less than 40 mg/dL, 2.7% of patients had 30 mg/dL or greater 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 and Relevance: In this cross-sectional study, the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400 to 799 mg/dL. However, regardless of method used, caution is advised with LDL-C estimation in this triglyceride range.
AB - Importance: Low-density lipoprotein cholesterol (LDL-C) is typically estimated with the Friedewald or Martin/Hopkins equation; however, if triglyceride levels are 400 mg/dL or greater, laboratories reflexively perform direct LDL-C (dLDL-C) measurement. The use of direct chemical LDL-C assays and estimation of LDL-C via the National Institutes of Health Sampson equation are not well validated, and data on the accuracy of LDL-C estimation at higher triglyceride levels are limited. Objective: To compare an extended Martin/Hopkins equation for triglyceride values of 400 to 799 mg/dL with the Friedewald and Sampson equations. Design, Setting, and Participants: This cross-sectional study evaluated consecutive patients at clinical sites across the US with patient lipid distributions representative of the US population in the Very Large Database of Lipids from January 1, 2006, to December 31, 2015, with triglyceride levels of 400 to 799 mg/dL. Data analysis was performed from November 9, 2020, to March 23, 2021. Main Outcomes and Measures: Accuracy in LDL-C classification according to guideline-based categories and absolute errors between estimated LDL-C and 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. Results: A total of 111939 patients (mean [SD] age, 52 [13] years; 65.0% male) with triglyceride levels of 400 to 799 mg/dL were included, representing 2.2% of 5081680 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 less than 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 less than 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 less than 40 mg/dL, 2.7% of patients had 30 mg/dL or greater 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 and Relevance: In this cross-sectional study, the extended Martin/Hopkins equation offered greater LDL-C accuracy compared with the Friedewald and Sampson equations in patients with triglyceride levels of 400 to 799 mg/dL. However, regardless of method used, caution is advised with LDL-C estimation in this triglyceride range.
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U2 - 10.1001/jamanetworkopen.2021.28817
DO - 10.1001/jamanetworkopen.2021.28817
M3 - Article
C2 - 34709388
AN - SCOPUS:85118572745
SN - 2574-3805
VL - 4
JO - JAMA network open
JF - JAMA network open
IS - 10
M1 - e2128817
ER -