Publication: Comparison of Low-Density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation: Insights From the FOURIER Trial.
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Identifiers
Date
2018-04-28
Authors
Martin, Seth S
Giugliano, Robert P
Murphy, Sabina A
Wasserman, Scott M
Stein, Evan A
Ceška, Richard
Lopez-Miranda, Jose
Georgiev, Borislav
Lorenzatti, Alberto J
Tikkanen, Matti J
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
American Medical Association
Abstract
Recent studies have shown that Friedewald underestimates low-density lipoprotein cholesterol (LDL-C) at lower levels, which could result in undertreatment of high-risk patients. A novel method (Martin/Hopkins) using a patient-specific conversion factor provides more accurate LDL-C levels. However, this method has not been tested in proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor-treated patients. To investigate accuracy of 2 different methods for estimating LDL-C levels (Martin/Hopkins and Friedewald) compared with gold standard preparative ultracentrifugation (PUC) in patients with low LDL-C levels in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk (FOURIER) trial. The FOURIER trial was a randomized clinical trial of evolocumab vs placebo added to statin therapy in 27 564 patients with stable atherosclerotic cardiovascular disease. The patients' LDL-C levels were assessed at baseline, 4 weeks, 12 weeks, 24 weeks, and every 24 weeks thereafter, and measured directly by PUC when the level was less than 40 mg/dL per the Friedewald method (calculated as non-HDL-C level - triglycerides/5). In the Martin/Hopkins method, patient-specific ratios of triglycerides to very low-density lipoprotein cholesterol (VLDL-C) ratios were determined and used to estimate VLDL-C, which was subtracted from the non-HDL-C level to obtain the LDL-C level. Low-density lipoprotein cholesterol calculated by the Friedewald and Martin/Hopkins methods, with PUC as the reference method. For this analysis, the mean (SD) age was 62.7 (9.0) years; 2885 of the 12 742 patients were women (22.6%). A total of 56 624 observations from 12 742 patients had Friedewald, Martin/Hopkins, and PUC LDL-C measurements. The median difference from PUC LDL-C levels for Martin/Hopkins LDL-C levels was -2 mg/dL (interquartile range [IQR], -4 to 1 mg/dL) and for Friedewald LDL-C levels was -4 mg/dL (IQR, -8 to -1 mg/dL; P In patients achieving low LDL-C with PCSK9 inhibition, the Martin/Hopkins method for LDL-C estimation more closely approximates gold standard PUC than Friedewald estimation does. The Martin/Hopkins method may prevent undertreatment because of LDL-C underestimation by the Friedewald method.
Description
MeSH Terms
Aged
Antibodies, monoclonal
Antibodies, monoclonal, humanized
Anticholesteremic agents
Atherosclerosis
Cholesterol, HDL
Cholesterol, LDL
Cholesterol, VLDL
Female
Humans
Hyperlipidemias
Male
Middle aged
Antibodies, monoclonal
Antibodies, monoclonal, humanized
Anticholesteremic agents
Atherosclerosis
Cholesterol, HDL
Cholesterol, LDL
Cholesterol, VLDL
Female
Humans
Hyperlipidemias
Male
Middle aged
DeCS Terms
Anticolesterolemiantes
Anticuerpos monoclonales
Anticuerpos monoclonales humanizados
Aterosclerosis
HDL-colesterol
Hiperlipidemias
LDL-colesterol
VLDL-colesterol
Anticuerpos monoclonales
Anticuerpos monoclonales humanizados
Aterosclerosis
HDL-colesterol
Hiperlipidemias
LDL-colesterol
VLDL-colesterol
CIE Terms
Keywords
Randomized controlled trials as topic, Risk assessment, Statistics as topic, Triglycerides, Ultracentrifugation
Citation
Martin SS, Giugliano RP, Murphy SA, Wasserman SM, Stein EA, Ceška R, et al. Comparison of Low-Density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation: Insights From the FOURIER Trial. JAMA Cardiol. 2018 Aug 1;3(8):749-753