TY - JOUR
T1 - Characterization of lipoprotein profiles in patients with hypertriglyceridemic Fredrickson-Levy and Lees dyslipidemia phenotypes
T2 - The very large database of Lipids studies 6 and 7
AU - Quispe, Renato
AU - Hendrani, Aditya D.
AU - Baradaran-Noveiry, Behnoud
AU - Martin, Seth S.
AU - Brown, Emily
AU - Kulkarni, Krishnaji R.
AU - Banach, Maciej
AU - Toth, Peter P.
AU - Brinton, Eliot A.
AU - Jones, Steven R.
AU - Joshi, Parag H.
N1 - Funding Information:
Drs. Martin and Jones are listed as coinventors on a pending patent filed by Johns Hopkins University for LDL-C estimation. Dr Jones has served as an advisor to Sano/Regeneron. Dr Martin has served as a consultant to Quest Diagnostics, Sano/Regeneron, Amgen, and the Pew Research Center. Dr. Joshi received non-compensated site PI for studies funded by AstraZeneca, Pfizer, Merck and Regeneron/Sanofi as well as modest consulting income from Regeneron. Dr. Toth has served as consultant and speaker for Amarin, Amgen, Kowa, Merck, Novo-Nordisk, Regeneron, and Sanofi; consultant to Gemphire. Dr. Brinton has received research support from Amarin, Kowa and the National Institutes of Health; honoraria as consultant for Akcea, Alexion, Amarin, Amgen, Janssen, Kastle, Kowa, Merck, Precision Biosciences, PTS Diagnostics, Regeneron, Sanofi-Aventis; honoraria as speaker for Akcea, Alexion, Amarin, Am-gen, Boehringer-Ingelheim, Janssen, Kastle, Kowa, Merck, Novo-Nordisk, Regeneron, Sanofi-Aventis.
Publisher Copyright:
Copyright © 2019 Termedia & Banach
PY - 2019
Y1 - 2019
N2 - Introduction: The association between triglycerides (TG) and cardiovascular diseases is complex. The classification of hypertriglyceridemic (HTG) phenotypes proposed by Fredrickson, Levy and Lees (FLL) helps inform treatment strategies. We aimed to describe levels of several lipoprotein variables from individuals with HTG FLL phenotypes from the Very Large Database of Lipids. Material and methods: We included fasting samples from 979,539 individuals from a contemporary large study population of US adults. Lipids were directly measured by density-gradient ultracentrifugation using the Vertical Auto Profile test while TG levels were measured in whole plasma using the Abbott ARCHITECT C-8000 system. Hyperchylomicronemic (Hyper-CM) and non-chylomicronemic (non-CM) phenotypes were defined using computationally derived models. Individuals with FLL type IIa phenotype were excluded. Distributions of lipid variables were compared using medians and Kruskal-Wallis test. Results: A total of 11.9% (n = 116,925) of individuals met criteria for HTG FLL phenotypes. Those with hyper-CM phenotypes (n = 5, < 0.1% of population) had two-fold higher TG levels compared with non-chylomicronemic (non-CM) individuals (11.9% of population) (p < 0.001). Type IIb individuals had the highest non-HDL-C levels (median 242 mg/dl). Cholesterol in large VLDL1+2 particles was higher than in small VLDL3 particles in all phenotypes except FLL type III. Hyper-CM phenotypes had significantly lower HDL-C levels but greater HDL2/HDL3-C ratio compared to non-CM phenotypes. Cholesterol content of the lipoprotein (a) peak was significantly higher in the hyper-CM groups compared to non-CM phenotypes (p < 0.0001). Conclusions: This observational hypothesis-generating study provides insight into the complexity of lipid metabolism in HTG phenotypes, including less traditional lipid measures such as LDL density, HDL subclasses and Lp(a)-C.
AB - Introduction: The association between triglycerides (TG) and cardiovascular diseases is complex. The classification of hypertriglyceridemic (HTG) phenotypes proposed by Fredrickson, Levy and Lees (FLL) helps inform treatment strategies. We aimed to describe levels of several lipoprotein variables from individuals with HTG FLL phenotypes from the Very Large Database of Lipids. Material and methods: We included fasting samples from 979,539 individuals from a contemporary large study population of US adults. Lipids were directly measured by density-gradient ultracentrifugation using the Vertical Auto Profile test while TG levels were measured in whole plasma using the Abbott ARCHITECT C-8000 system. Hyperchylomicronemic (Hyper-CM) and non-chylomicronemic (non-CM) phenotypes were defined using computationally derived models. Individuals with FLL type IIa phenotype were excluded. Distributions of lipid variables were compared using medians and Kruskal-Wallis test. Results: A total of 11.9% (n = 116,925) of individuals met criteria for HTG FLL phenotypes. Those with hyper-CM phenotypes (n = 5, < 0.1% of population) had two-fold higher TG levels compared with non-chylomicronemic (non-CM) individuals (11.9% of population) (p < 0.001). Type IIb individuals had the highest non-HDL-C levels (median 242 mg/dl). Cholesterol in large VLDL1+2 particles was higher than in small VLDL3 particles in all phenotypes except FLL type III. Hyper-CM phenotypes had significantly lower HDL-C levels but greater HDL2/HDL3-C ratio compared to non-CM phenotypes. Cholesterol content of the lipoprotein (a) peak was significantly higher in the hyper-CM groups compared to non-CM phenotypes (p < 0.0001). Conclusions: This observational hypothesis-generating study provides insight into the complexity of lipid metabolism in HTG phenotypes, including less traditional lipid measures such as LDL density, HDL subclasses and Lp(a)-C.
KW - Dyslipidemia
KW - Fredrickson-Levy phenotypes
KW - Hypertriglyceridemia
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U2 - 10.5114/aoms.2019.87207
DO - 10.5114/aoms.2019.87207
M3 - Article
C2 - 31572464
AN - SCOPUS:85072178988
SN - 1734-1922
VL - 15
SP - 1195
EP - 1202
JO - Archives of Medical Science
JF - Archives of Medical Science
IS - 5
ER -