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

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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

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