Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population

UCLEB Consortium; Jorgen Engmann; Tom R Gaunt; Deborah A. Lawlor; Olia Papacosta; Tina Shah; Therese Tillin; Peter H Whincup; Nishi Chaturvedi; Mika Kivimaki; Diana Kuh; Meena Kumari; Alun D. Hughes; Juan P Casas; Steve E Humphries; Aroon D Hingorani; A Floriaan Schmidt

doi:10.1177/0004563220961753

Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population

UCLEB Consortium, Jorgen Engmann, Tom R Gaunt, Deborah A. Lawlor, Olia Papacosta, Tina Shah, Therese Tillin, Peter H Whincup, Nishi Chaturvedi, Mika Kivimaki, Diana Kuh, Meena Kumari, Alun D. Hughes, Juan P Casas, Steve E Humphries, Aroon D Hingorani, A Floriaan Schmidt

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Abstract

Background Nuclear magnetic resonance allows triglycerides (TG) to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these sub-fractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 TG-containing lipoprotein sub-fraction metabolites. Methods Lipoprotein sub-fractions using the Nightingale NMR platform were measured in 9,073 participants from 4 cohort studies contributing to the UCL-Edinburgh-Bristol (UCLEB) consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for in a disease-free population sex, age (<55, 55-65, >65 years), and in a subgroup population of subjects with cardiovascular disease (CVD) or type 2 diabetes (T2DM). We also determined the distribution across BMI and smoking status. Results The largest reference interval range was observed in the medium VLDL sub-class (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among men and women, with the exception of TG in HDL. TG sub-fraction concentrations in VLDL, IDL, LDL and HDL sub-classes increased with increasing age and increasing BMI. TG sub-fraction concentrations were significantly higher in ever smokers compared to never smokers and among those with clinical chemistry measured total TG greater than 1.7 mmol/L, in those with CVD and, T2DM as compared to disease free subjects. Conclusion This is the first study to establish reference interval ranges for 14 TG-containing lipoprotein sub-fractions in samples from the general population measured using the NMR platform. The utility of NMR lipid measures may lead to greater insights for the role of TG in CVD, emphasising the importance of appropriate reference interval ranges for future clinical decision making.

Original language	English
Journal	Annals of Clinical Biochemistry
Early online date	21 Oct 2020
DOIs	https://doi.org/10.1177/0004563220961753 https://doi.org/10.1177/0004563220961753
Publication status	Published - 5 Jan 2021

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UCLEB Consortium, Engmann, J., Gaunt, T. R., Lawlor, D. A., Papacosta, O., Shah, T., Tillin, T., Whincup, P. H., Chaturvedi, N., Kivimaki, M., Kuh, D., Kumari, M., Hughes, A. D., Casas, J. P., Humphries, S. E., Hingorani, A. D., & Schmidt, A. F. (2021). Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population. Annals of Clinical Biochemistry. https://doi.org/10.1177/0004563220961753, https://doi.org/10.1177/0004563220961753

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title = "Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population",

abstract = "Background Nuclear magnetic resonance allows triglycerides (TG) to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these sub-fractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 TG-containing lipoprotein sub-fraction metabolites. Methods Lipoprotein sub-fractions using the Nightingale NMR platform were measured in 9,073 participants from 4 cohort studies contributing to the UCL-Edinburgh-Bristol (UCLEB) consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for in a disease-free population sex, age (<55, 55-65, >65 years), and in a subgroup population of subjects with cardiovascular disease (CVD) or type 2 diabetes (T2DM). We also determined the distribution across BMI and smoking status. Results The largest reference interval range was observed in the medium VLDL sub-class (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among men and women, with the exception of TG in HDL. TG sub-fraction concentrations in VLDL, IDL, LDL and HDL sub-classes increased with increasing age and increasing BMI. TG sub-fraction concentrations were significantly higher in ever smokers compared to never smokers and among those with clinical chemistry measured total TG greater than 1.7 mmol/L, in those with CVD and, T2DM as compared to disease free subjects. Conclusion This is the first study to establish reference interval ranges for 14 TG-containing lipoprotein sub-fractions in samples from the general population measured using the NMR platform. The utility of NMR lipid measures may lead to greater insights for the role of TG in CVD, emphasising the importance of appropriate reference interval ranges for future clinical decision making. ",

author = "{UCLEB Consortium} and Roshni Joshi and Wannamethee, {S Goya} and Jorgen Engmann and Gaunt, {Tom R} and Lawlor, {Deborah A.} and Price, {Jacqueline F.} and Olia Papacosta and Tina Shah and Therese Tillin and Whincup, {Peter H} and Nishi Chaturvedi and Mika Kivimaki and Diana Kuh and Meena Kumari and Hughes, {Alun D.} and Casas, {Juan P} and Humphries, {Steve E} and Hingorani, {Aroon D} and Schmidt, {A Floriaan}",

year = "2021",

month = jan,

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doi = "10.1177/0004563220961753",

language = "English",

journal = "Annals of Clinical Biochemistry",

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UCLEB Consortium, Engmann, J, Gaunt, TR, Lawlor, DA, Papacosta, O, Shah, T, Tillin, T, Whincup, PH, Chaturvedi, N, Kivimaki, M, Kuh, D, Kumari, M, Hughes, AD, Casas, JP, Humphries, SE, Hingorani, AD & Schmidt, AF 2021, 'Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population', Annals of Clinical Biochemistry. https://doi.org/10.1177/0004563220961753, https://doi.org/10.1177/0004563220961753

TY - JOUR

T1 - Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population

AU - UCLEB Consortium

AU - Joshi, Roshni

AU - Wannamethee, S Goya

AU - Engmann, Jorgen

AU - Gaunt, Tom R

AU - Lawlor, Deborah A.

AU - Price, Jacqueline F.

AU - Papacosta, Olia

AU - Shah, Tina

AU - Tillin, Therese

AU - Whincup, Peter H

AU - Chaturvedi, Nishi

AU - Kivimaki, Mika

AU - Kuh, Diana

AU - Kumari, Meena

AU - Hughes, Alun D.

AU - Casas, Juan P

AU - Humphries, Steve E

AU - Hingorani, Aroon D

AU - Schmidt, A Floriaan

PY - 2021/1/5

Y1 - 2021/1/5

N2 - Background Nuclear magnetic resonance allows triglycerides (TG) to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these sub-fractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 TG-containing lipoprotein sub-fraction metabolites. Methods Lipoprotein sub-fractions using the Nightingale NMR platform were measured in 9,073 participants from 4 cohort studies contributing to the UCL-Edinburgh-Bristol (UCLEB) consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for in a disease-free population sex, age (<55, 55-65, >65 years), and in a subgroup population of subjects with cardiovascular disease (CVD) or type 2 diabetes (T2DM). We also determined the distribution across BMI and smoking status. Results The largest reference interval range was observed in the medium VLDL sub-class (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among men and women, with the exception of TG in HDL. TG sub-fraction concentrations in VLDL, IDL, LDL and HDL sub-classes increased with increasing age and increasing BMI. TG sub-fraction concentrations were significantly higher in ever smokers compared to never smokers and among those with clinical chemistry measured total TG greater than 1.7 mmol/L, in those with CVD and, T2DM as compared to disease free subjects. Conclusion This is the first study to establish reference interval ranges for 14 TG-containing lipoprotein sub-fractions in samples from the general population measured using the NMR platform. The utility of NMR lipid measures may lead to greater insights for the role of TG in CVD, emphasising the importance of appropriate reference interval ranges for future clinical decision making.

AB - Background Nuclear magnetic resonance allows triglycerides (TG) to be subclassified into 14 different classes based on particle size and lipid content. We recently showed that these sub-fractions have differential associations with cardiovascular disease events. Here we report the distributions and define reference interval ranges for 14 TG-containing lipoprotein sub-fraction metabolites. Methods Lipoprotein sub-fractions using the Nightingale NMR platform were measured in 9,073 participants from 4 cohort studies contributing to the UCL-Edinburgh-Bristol (UCLEB) consortium. The distribution of each metabolite was assessed, and reference interval ranges were calculated for in a disease-free population sex, age (<55, 55-65, >65 years), and in a subgroup population of subjects with cardiovascular disease (CVD) or type 2 diabetes (T2DM). We also determined the distribution across BMI and smoking status. Results The largest reference interval range was observed in the medium VLDL sub-class (2.5th 97.5th percentile; 0.08 to 0.68 mmol/L). The reference intervals were comparable among men and women, with the exception of TG in HDL. TG sub-fraction concentrations in VLDL, IDL, LDL and HDL sub-classes increased with increasing age and increasing BMI. TG sub-fraction concentrations were significantly higher in ever smokers compared to never smokers and among those with clinical chemistry measured total TG greater than 1.7 mmol/L, in those with CVD and, T2DM as compared to disease free subjects. Conclusion This is the first study to establish reference interval ranges for 14 TG-containing lipoprotein sub-fractions in samples from the general population measured using the NMR platform. The utility of NMR lipid measures may lead to greater insights for the role of TG in CVD, emphasising the importance of appropriate reference interval ranges for future clinical decision making.

U2 - 10.1177/0004563220961753

DO - 10.1177/0004563220961753

M3 - Article

SN - 0004-5632

JO - Annals of Clinical Biochemistry

JF - Annals of Clinical Biochemistry

ER -

Establishing reference intervals for triglyceride containing lipoprotein sub-fraction metabolites measured using Nuclear Magnetic Resonance Spectroscopy in a UK population

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