Modern prevalence of dysbetalipoproteinemia (Fredrickson-Levy-Lees type III hyperlipoproteinemia)

Vincent A Pallazola, Vasanth Sathiyakumar, Jihwan Park, Rachit M Vakil, Peter P Toth, Mariana Lazo-Elizondo, Emily Brown, Renato Quispe, Eliseo Guallar, Maciej Banach, Roger S Blumenthal, Steven R Jones, David Marais, Daniel Soffer, Allan D Sniderman, Seth S Martin, Vincent A Pallazola, Vasanth Sathiyakumar, Jihwan Park, Rachit M Vakil, Peter P Toth, Mariana Lazo-Elizondo, Emily Brown, Renato Quispe, Eliseo Guallar, Maciej Banach, Roger S Blumenthal, Steven R Jones, David Marais, Daniel Soffer, Allan D Sniderman, Seth S Martin

Abstract

Introduction: Dysbetalipoproteinaemia (HLP3) is a disorder characterized by excess cholesterol-enriched, triglyceride-rich lipoprotein remnants in genetically predisposed individuals that powerfully promote premature cardiovascular disease if untreated. The current prevalence of HLP3 is largely unknown.

Material and methods: We performed cross-sectional analysis of 128,485 U.S. adults from the Very Large Database of Lipids (VLDbL), using four algorithms to diagnose HLP3 employing three Vertical Auto Profile ultracentrifugation (UC) criteria and a previously described apolipoprotein B (apoB) method. We evaluated 4,926 participants from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) with the apoB method. We examined demographic and lipid characteristics stratified by presence of HLP3 and evaluated lipid characteristics in those with HLP3 phenotype discordance and concordance as determined by apoB and originally defined UC criteria 1.

Results: In U.S. adults in VLDbL and NHANES, a 1.7-2.0% prevalence is observed for HLP3 with the novel apoB method as compared to 0.2-0.8% prevalence in VLDbL via UC criteria 1-3. Participants who were both apoB and UC criteria HLP3 positive had higher remnant particles as well as more elevated triglyceride/apoB and total cholesterol/apoB ratios (all p < 0.001) than those who were apoB method positive and UC criteria 1 negative.

Conclusions: HLP3 may be more prevalent than historically and clinically appreciated. The apoB method increases HLP3 identification via inclusion of milder phenotypes. Further work should evaluate the clinical implications of HLP3 diagnosis at various lipid algorithm cut-points to evaluate the ideal standard in the modern era.

Keywords: National Health and Nutrition Examination Survey; Very Large Database of Lipids (VLDL); apolipoprotein B; dysbetalipoproteinemia; type III hyperlipoproteinemia.

Conflict of interest statement

VAP, VS, JP, RMV, MLE, EB, RQ, EG, MB, RSB, DM and ADS have no relevant disclosures. PPT: Speakers Bureau; Amarin, Akcea, Amgen, Kowa, Merck, Nova Nordisk, Regeneron, Sanofi (Consultant/Advisory Board). SRJ: Co-inventor for a method to estimate LDL cholesterol levels, patent application pending; funding from the David and June Trone Family Foundation. DS: personal fees from Amgen Inc, Akcea Therapeutics, Medicure, Sanofi, Regeneron; personal fees from the National Lipid Association outside the submitted work. SSM: Co-inventor for a method to estimate LDL cholesterol levels, patent application pending; Consultant/Advisory Board for Sanofi/Regeneron, Amgen, Quest Diagnostics, Akcea, Novo Nordisk, Esperion.

Copyright: © 2019 Termedia & Banach.

Figures

Figure 1
Figure 1
Study population selection criteria ApoB – apolipoprotein B, NHANES – National Health and Nutrition Examination Survey.
Figure 2
Figure 2
Dyslipidemia classification schemat ApoB – apolipoprotein B, HLP3 – type III familial hyperlipoproteinemias phenotype, LDL-Cr – real (biologic) low-density lipoprotein-cholesterol, TG – triglycerides, VLDL-C – very low-density lipoprotein cholesterol.
Figure 3
Figure 3
Comparison of lipid and lipoprotein cholesterol distributions between the Very Large Database of Lipids study and 2011–2012 National Health and Nutrition Examination Survey Lipid distribution between apoB data (n = 128,485) and NHANES 2011–2012 data (n = 2,415). NHANES participants are depicted by dotted lines; VLDbL patients are depicted by solid lines. ApoB – apolipoprotein B, NHANES – National Health and Nutrition Examination Survey.

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Source: PubMed

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