Lipoprotein characteristics and incident coronary heart disease: prospective cohort of nearly 90 000 individuals in UK Biobank

Background: associations of coronary heart disease (CHD) with plasma lipids are well described, but the associations with characteristics of lipoproteins (which transport lipids) remain unclear.

Methods and Results: UK Biobank is a prospective study of 0.5 million adults. Analyses were restricted to 89 422 participants with plasma lipoprotein and apolipoprotein measures from Nightingale nuclear magnetic resonance spectroscopy and without CHD at baseline. CHD risk was positively associated with concentrations of very‐low‐density lipoproteins, intermediate‐density lipoproteins, and low‐density lipoproteins (LDL), and inversely associated with high‐density lipoproteins. Hazard ratios (99% CIs) per SD were 1.22 (1.17–1.28), 1.16 (1.11–1.21), 1.20 (1.15–1.25), and 0.90 (0.86–0.95), respectively. Larger subclasses of very‐low‐density lipoproteins were less strongly associated with CHD risk, but associations did not materially vary by size of LDL or high‐density lipoprotein. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles. Apolipoprotein B was highly correlated with LDL concentration (r=0.99), but after adjustment for apolipoprotein B, concentrations of very‐low‐density lipoprotein and high‐density lipoprotein particles remained strongly related to CHD risk.

Conclusions: this large‐scale study reliably quantifies the associations of nuclear magnetic resonance–defined lipoprotein characteristics with CHD risk. CHD risk was most strongly related to particle concentrations, and separate measurements of lipoprotein concentrations may be of greater value than the measurement by apolipoprotein B, which was largely determined by LDL concentration alone. Furthermore, there was strong evidence of positive association with mean triglyceride molecules per LDL particle but little evidence of associations with total triglycerides or other lipid and lipoprotein fractions after accounting for lipoprotein concentrations.

UK biobank, apolipoproteins, cholesterol, coronary heart disease, lipoproteins, nuclear magnetic resonance, triglycerides

10.1161/JAHA.123.029552

Jin, Danyao

3b4bb056-3dc1-4729-80ce-602181221e28

Trichia, Eirini

305f7339-910c-4834-b4f6-f1a697f8b361

Islam, Nazrul

e5345196-7479-438f-b4f6-c372d2135586

Bešević, Jelena

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Lewington, Sarah

b47fcba0-25ce-481a-81c6-5b30ea95ae34

Lacey, Ben

38227149-1faa-42d3-bf28-a9345d0c0872

17 October 2023

Jin, Danyao

3b4bb056-3dc1-4729-80ce-602181221e28

Trichia, Eirini

305f7339-910c-4834-b4f6-f1a697f8b361

Islam, Nazrul

e5345196-7479-438f-b4f6-c372d2135586

Bešević, Jelena

662ef865-ff3a-42cb-988c-1271e5e57ae8

Lewington, Sarah

b47fcba0-25ce-481a-81c6-5b30ea95ae34

Lacey, Ben

38227149-1faa-42d3-bf28-a9345d0c0872

Jin, Danyao, Trichia, Eirini, Islam, Nazrul, Bešević, Jelena, Lewington, Sarah and Lacey, Ben (2023) Lipoprotein characteristics and incident coronary heart disease: prospective cohort of nearly 90 000 individuals in UK Biobank. Journal of the American Heart Association, 12 (20), [e029552]. (doi:10.1161/JAHA.123.029552).

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Accepted/In Press date: 18 September 2023

e-pub ahead of print date: 10 October 2023

Published date: 17 October 2023

Additional Information: Funding Information: The Clinical Trial Service Unit and Epidemiological Studies Unit receives research grants from industry that are governed by University of Oxford contracts that protect its independence and has a staff policy of not taking personal payments from industry; further details can be found at https:// www.ndph.ox.ac.uk/files/about/ndph-independence-of-research-polic y-jun-20.pdf. This research used UK Biobank data assets made available by National Safe Haven as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant reference MC_PC_20058). Funding Information: This research used the UK Biobank resource (application number 30418). We appreciate the participants of UK Biobank for their contribution to the resource. This work uses data provided by patients and collected by the National Health Service as part of their care and support. Nightingale Health Plc approved the use of data from application 30418. Sources of Funding The Clinical Trial Service Unit and Epidemiological Studies Unit receives research grants from industry that are governed by University of Oxford contracts that protect its independence and has a staff policy of not taking personal payments from industry; further details can be found at https:// www.ndph.ox.ac.uk/files/about/ndph-independence-of-research-polic y-jun-20.pdf. This research used UK Biobank data assets made available by National Safe Haven as part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant reference MC_PC_20058). Funding Information: Dr Lewington reports grants from the Medical Research Council and research funding from the US Centers for Disease Control and Prevention Foundation (with support from Amgen) and from the World Health Organization during the conduct of the study. The remaining authors have no disclosures to report. Publisher Copyright: © 2023 The Authors.

Keywords: UK biobank, apolipoproteins, cholesterol, coronary heart disease, lipoproteins, nuclear magnetic resonance, triglycerides

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