Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol <70 mg/dL compared with a novel low-density lipoprotein estimation method

Seamus Whelton, Jeffrey W. Meeusen, Leslie J. Donato, Allan S. Jaffe, Amy Saenger, Lori J Sokoll, Roger S Blumenthal, Steven Jones, Seth Martin

Research output: Contribution to journalArticle

Abstract

Background A number of national and international guidelines recommend treatment to low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. Comparing the performance of the Friedewald and a novel LDL-C estimate at these concentrations in a nationally representative and clinical cohorts can inform best practices. Objectives The objectives of the study were to evaluate concordance between Friedewald-estimated LDL-C and novel-estimated LDL-C and compare with other atherogenic parameters when the estimated LDL-C is <70 mg/dL. Methods Atherogenic lipid parameters were assessed in a cross-sectional analysis among participants with a Friedewald-estimated LDL-C <70 mg/dL from National Health and Nutrition Examination Survey (NHANES) 2011–2012 (n = 334), Johns Hopkins (n = 896), and Mayo Clinic (n = 1151). Novel LDL-C was estimated using an individualized factor to account for heterogeneity in the triglyceride to very low-density lipoprotein cholesterol ratio. Participants were classified as concordant if their LDL-C was <70 mg/dL by both equations and discordant if ≥70 mg/dL by the novel equation. Results Among NHANES participants not on statin therapy, 10% had LDL-C <70 mg/dL by both the Friedewald and novel equations. Overall, 15% of participants from NHANES, 20% from Johns Hopkins, and 20% from Mayo Clinic had discordant LDL-C values. In all 3 cohorts, nearly one-fourth of participants in the discordant group had an LDL-C estimate of ≥80 mg/dL (ie, ≥10 mg/dL higher) by the novel equation. Compared with the concordant group, the discordant group had significantly higher median concentrations of non-high-density lipoprotein cholesterol (HDL-C; 101–104 mg/dL vs 74–79 mg/dL) and apolipoprotein B (apoB; 65–72 mg/dL vs 47–57 mg/dL). In NHANES, wherein statins use was recorded, a similarly higher atherogenic burden by non-HDL-C and apoB levels was observed on and off statin therapy in the discordant group. Conclusions In a nationally representative sample, a hospital laboratory, and a reference laboratory, approximately one-fifth of individuals with Friedewald-estimated LDL-C <70 mg/dL have a value ≥70 mg/dL using the novel LDL-C equation. These individuals also have significantly higher non-HDL-C and apoB concentrations, conferring an increased risk for cardiovascular disease. Accordingly, ongoing use of Friedewald estimation may lead to the misclassification of high-risk individuals and subsequent under-utilization of lipid-lowering therapies. Further investigations are necessary to confirm these findings in patients using proprotein convertase subtilisin-kexin type 9 inhibitors.

Original languageEnglish (US)
Pages (from-to)1065-1072
Number of pages8
JournalJournal of Clinical Lipidology
Volume11
Issue number4
DOIs
StatePublished - Jul 1 2017

Fingerprint

LDL Lipoproteins
LDL Cholesterol
Nutrition Surveys
Apolipoproteins B
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipids
VLDL Cholesterol
Hospital Laboratories
Practice Guidelines
Triglycerides
Cardiovascular Diseases
Therapeutics
Cross-Sectional Studies
Guidelines

Keywords

  • ApoB
  • ASCVD
  • LDL-C
  • Lipids
  • Non-HDL-C
  • PCSK9

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Cite this

@article{91d72897e6764506b5a708c6c1c3666d,
title = "Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol <70 mg/dL compared with a novel low-density lipoprotein estimation method",
abstract = "Background A number of national and international guidelines recommend treatment to low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. Comparing the performance of the Friedewald and a novel LDL-C estimate at these concentrations in a nationally representative and clinical cohorts can inform best practices. Objectives The objectives of the study were to evaluate concordance between Friedewald-estimated LDL-C and novel-estimated LDL-C and compare with other atherogenic parameters when the estimated LDL-C is <70 mg/dL. Methods Atherogenic lipid parameters were assessed in a cross-sectional analysis among participants with a Friedewald-estimated LDL-C <70 mg/dL from National Health and Nutrition Examination Survey (NHANES) 2011–2012 (n = 334), Johns Hopkins (n = 896), and Mayo Clinic (n = 1151). Novel LDL-C was estimated using an individualized factor to account for heterogeneity in the triglyceride to very low-density lipoprotein cholesterol ratio. Participants were classified as concordant if their LDL-C was <70 mg/dL by both equations and discordant if ≥70 mg/dL by the novel equation. Results Among NHANES participants not on statin therapy, 10{\%} had LDL-C <70 mg/dL by both the Friedewald and novel equations. Overall, 15{\%} of participants from NHANES, 20{\%} from Johns Hopkins, and 20{\%} from Mayo Clinic had discordant LDL-C values. In all 3 cohorts, nearly one-fourth of participants in the discordant group had an LDL-C estimate of ≥80 mg/dL (ie, ≥10 mg/dL higher) by the novel equation. Compared with the concordant group, the discordant group had significantly higher median concentrations of non-high-density lipoprotein cholesterol (HDL-C; 101–104 mg/dL vs 74–79 mg/dL) and apolipoprotein B (apoB; 65–72 mg/dL vs 47–57 mg/dL). In NHANES, wherein statins use was recorded, a similarly higher atherogenic burden by non-HDL-C and apoB levels was observed on and off statin therapy in the discordant group. Conclusions In a nationally representative sample, a hospital laboratory, and a reference laboratory, approximately one-fifth of individuals with Friedewald-estimated LDL-C <70 mg/dL have a value ≥70 mg/dL using the novel LDL-C equation. These individuals also have significantly higher non-HDL-C and apoB concentrations, conferring an increased risk for cardiovascular disease. Accordingly, ongoing use of Friedewald estimation may lead to the misclassification of high-risk individuals and subsequent under-utilization of lipid-lowering therapies. Further investigations are necessary to confirm these findings in patients using proprotein convertase subtilisin-kexin type 9 inhibitors.",
keywords = "ApoB, ASCVD, LDL-C, Lipids, Non-HDL-C, PCSK9",
author = "Seamus Whelton and Meeusen, {Jeffrey W.} and Donato, {Leslie J.} and Jaffe, {Allan S.} and Amy Saenger and Sokoll, {Lori J} and Blumenthal, {Roger S} and Steven Jones and Seth Martin",
year = "2017",
month = "7",
day = "1",
doi = "10.1016/j.jacl.2017.05.005",
language = "English (US)",
volume = "11",
pages = "1065--1072",
journal = "Journal of Clinical Lipidology",
issn = "1933-2874",
publisher = "Elsevier BV",
number = "4",

}

TY - JOUR

T1 - Evaluating the atherogenic burden of individuals with a Friedewald-estimated low-density lipoprotein cholesterol <70 mg/dL compared with a novel low-density lipoprotein estimation method

AU - Whelton, Seamus

AU - Meeusen, Jeffrey W.

AU - Donato, Leslie J.

AU - Jaffe, Allan S.

AU - Saenger, Amy

AU - Sokoll, Lori J

AU - Blumenthal, Roger S

AU - Jones, Steven

AU - Martin, Seth

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Background A number of national and international guidelines recommend treatment to low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. Comparing the performance of the Friedewald and a novel LDL-C estimate at these concentrations in a nationally representative and clinical cohorts can inform best practices. Objectives The objectives of the study were to evaluate concordance between Friedewald-estimated LDL-C and novel-estimated LDL-C and compare with other atherogenic parameters when the estimated LDL-C is <70 mg/dL. Methods Atherogenic lipid parameters were assessed in a cross-sectional analysis among participants with a Friedewald-estimated LDL-C <70 mg/dL from National Health and Nutrition Examination Survey (NHANES) 2011–2012 (n = 334), Johns Hopkins (n = 896), and Mayo Clinic (n = 1151). Novel LDL-C was estimated using an individualized factor to account for heterogeneity in the triglyceride to very low-density lipoprotein cholesterol ratio. Participants were classified as concordant if their LDL-C was <70 mg/dL by both equations and discordant if ≥70 mg/dL by the novel equation. Results Among NHANES participants not on statin therapy, 10% had LDL-C <70 mg/dL by both the Friedewald and novel equations. Overall, 15% of participants from NHANES, 20% from Johns Hopkins, and 20% from Mayo Clinic had discordant LDL-C values. In all 3 cohorts, nearly one-fourth of participants in the discordant group had an LDL-C estimate of ≥80 mg/dL (ie, ≥10 mg/dL higher) by the novel equation. Compared with the concordant group, the discordant group had significantly higher median concentrations of non-high-density lipoprotein cholesterol (HDL-C; 101–104 mg/dL vs 74–79 mg/dL) and apolipoprotein B (apoB; 65–72 mg/dL vs 47–57 mg/dL). In NHANES, wherein statins use was recorded, a similarly higher atherogenic burden by non-HDL-C and apoB levels was observed on and off statin therapy in the discordant group. Conclusions In a nationally representative sample, a hospital laboratory, and a reference laboratory, approximately one-fifth of individuals with Friedewald-estimated LDL-C <70 mg/dL have a value ≥70 mg/dL using the novel LDL-C equation. These individuals also have significantly higher non-HDL-C and apoB concentrations, conferring an increased risk for cardiovascular disease. Accordingly, ongoing use of Friedewald estimation may lead to the misclassification of high-risk individuals and subsequent under-utilization of lipid-lowering therapies. Further investigations are necessary to confirm these findings in patients using proprotein convertase subtilisin-kexin type 9 inhibitors.

AB - Background A number of national and international guidelines recommend treatment to low-density lipoprotein cholesterol (LDL-C) <70 mg/dL. Comparing the performance of the Friedewald and a novel LDL-C estimate at these concentrations in a nationally representative and clinical cohorts can inform best practices. Objectives The objectives of the study were to evaluate concordance between Friedewald-estimated LDL-C and novel-estimated LDL-C and compare with other atherogenic parameters when the estimated LDL-C is <70 mg/dL. Methods Atherogenic lipid parameters were assessed in a cross-sectional analysis among participants with a Friedewald-estimated LDL-C <70 mg/dL from National Health and Nutrition Examination Survey (NHANES) 2011–2012 (n = 334), Johns Hopkins (n = 896), and Mayo Clinic (n = 1151). Novel LDL-C was estimated using an individualized factor to account for heterogeneity in the triglyceride to very low-density lipoprotein cholesterol ratio. Participants were classified as concordant if their LDL-C was <70 mg/dL by both equations and discordant if ≥70 mg/dL by the novel equation. Results Among NHANES participants not on statin therapy, 10% had LDL-C <70 mg/dL by both the Friedewald and novel equations. Overall, 15% of participants from NHANES, 20% from Johns Hopkins, and 20% from Mayo Clinic had discordant LDL-C values. In all 3 cohorts, nearly one-fourth of participants in the discordant group had an LDL-C estimate of ≥80 mg/dL (ie, ≥10 mg/dL higher) by the novel equation. Compared with the concordant group, the discordant group had significantly higher median concentrations of non-high-density lipoprotein cholesterol (HDL-C; 101–104 mg/dL vs 74–79 mg/dL) and apolipoprotein B (apoB; 65–72 mg/dL vs 47–57 mg/dL). In NHANES, wherein statins use was recorded, a similarly higher atherogenic burden by non-HDL-C and apoB levels was observed on and off statin therapy in the discordant group. Conclusions In a nationally representative sample, a hospital laboratory, and a reference laboratory, approximately one-fifth of individuals with Friedewald-estimated LDL-C <70 mg/dL have a value ≥70 mg/dL using the novel LDL-C equation. These individuals also have significantly higher non-HDL-C and apoB concentrations, conferring an increased risk for cardiovascular disease. Accordingly, ongoing use of Friedewald estimation may lead to the misclassification of high-risk individuals and subsequent under-utilization of lipid-lowering therapies. Further investigations are necessary to confirm these findings in patients using proprotein convertase subtilisin-kexin type 9 inhibitors.

KW - ApoB

KW - ASCVD

KW - LDL-C

KW - Lipids

KW - Non-HDL-C

KW - PCSK9

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U2 - 10.1016/j.jacl.2017.05.005

DO - 10.1016/j.jacl.2017.05.005

M3 - Article

VL - 11

SP - 1065

EP - 1072

JO - Journal of Clinical Lipidology

JF - Journal of Clinical Lipidology

SN - 1933-2874

IS - 4

ER -