A new phenotypic classification system for dyslipidemias based on the standard lipid panel

Maureen Sampson,Jeff Meeusen,Sierra Wilson,Sotirios K Karathanasis,Leslie J Donato,Robert Shamburek,Anna Wolska,Daniel Soffer,Robert S Rosenson,Eliot A Brinton,Peter Wilson,James D Otvos,Erica Fatica,Marcelo Amar,Alan T Remaley,Rami A Ballout

doi:10.1186/s12944-021-01585-8

Abstract

BackgroundDyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing.ObjectiveTo develop a new algorithm for classifying lipoprotein disorders that only relies on the standard lipid panel.MethodsLipid thresholds for defining the different lipoprotein phenotypes were derived for Non-High-Density Lipoprotein-Cholesterol (NonHDL-C) and Triglycerides (TG) to be concordant when possible with the current US Multi-Society guidelines for blood cholesterol management.ResultsThe new classification method categorizes patients into all the classical Fredrickson-like phenotypes except for Type III dysbetalipoproteinemia. In addition, a new hypolipidemic phenotype (Type VI) due to genetic mutations in apoB-metabolism is described. The validity of the new algorithm was confirmed by lipid analysis by NMR (N = 11,365) and by concordance with classification by agarose gel electrophoresis/beta-quantification (N = 5504). Furthermore, based on the Atherosclerosis Risk in Communities (ARIC) cohort (N = 14,742), the lipoprotein phenotypes differ in their association with ASCVD (TypeV>IIb > IVb > IIa > IVa > normolipidemic) and can be used prognostically as risk enhancer conditions in the management of patients.ConclusionsWe describe a clinically useful lipoprotein phenotyping system that is only dependent upon the standard lipid panel. It, therefore, can be easily implemented for increasing compliance with current guidelines and for improving the care of patients at risk for ASCVD.

Highlights

Dyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing
We describe a clinically useful lipoprotein phenotyping system that is only dependent upon the standard lipid panel
A new algorithm is described for categorizing dyslipidemic patients into Fredrickson-like lipoprotein phenotypes except for Type III

Summary

Introduction

Dyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing. Most possible permutations for elevations in these lipoproteins, taken one or two at a time, comprise the classic Fredrickson classification system. Three of these phenotypes are characterized by an increase in a single type of lipoprotein, namely Type I (chylomicrons), Type IIa (LDL), and Type IV (VLDL). The only other possible permutation for simultaneous elevations in two lipoprotein classes would be an increase in LDL and chylomicrons, but this pattern has only been described in a single case report [7]. The other remaining Fredrickson phenotype is Type III It is a relatively uncommon disorder characterized by the accumulation of cholesterol-enriched remnant particles, due to impaired apoE-mediated hepatic clearance of partially lipolyzed VLDL and chylomicrons [8].

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