Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults
Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults
Objective: to examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.
Methods: competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.
Results: 258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).
Conclusions: lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.
Epidemiology, Magnetic Resonance Imaging, Risk Factors
Raisi-Estabragh, Zahra
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Cooper, Jackie
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Bethell, Mae S.
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McCracken, Celeste
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Lewandowski, Adam J.
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Leeson, Paul
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Neubauer, Stefan
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Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Petersen, Steffen E
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16 November 2022
Raisi-Estabragh, Zahra
43c85c5e-4574-476b-80d6-8fb1cdb3df0a
Cooper, Jackie
f78de577-4cac-496f-ad11-5f59dd305046
Bethell, Mae S.
c3af4794-abd4-47d6-bf1c-c0ee84741184
McCracken, Celeste
5d772e9e-3aaa-41da-a5ef-3943b1631fd9
Lewandowski, Adam J.
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Leeson, Paul
34dc217d-32e6-4c63-bcbb-334844939c92
Neubauer, Stefan
c8a34156-a4ed-4dfe-97cb-4f47627d927d
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Petersen, Steffen E
04f2ce88-790d-48dc-baac-cbe0946dd928
Raisi-Estabragh, Zahra, Cooper, Jackie, Bethell, Mae S., McCracken, Celeste, Lewandowski, Adam J., Leeson, Paul, Neubauer, Stefan, Harvey, Nicholas C. and Petersen, Steffen E
(2022)
Lower birth weight is linked to poorer cardiovascular health in middle-aged population-based adults.
Heart, [321733].
(doi:10.1136/heartjnl-2022-321733).
Abstract
Objective: to examine associations of birth weight with clinical and imaging indicators of cardiovascular health and evaluate mechanistic pathways in the UK Biobank.
Methods: competing risk regression was used to estimate associations of birth weight with incident myocardial infarction (MI) and mortality (all-cause, cardiovascular disease, ischaemic heart disease, MI), over 7-12 years of longitudinal follow-up, adjusting for age, sex, deprivation, maternal smoking/hypertension and maternal/paternal diabetes. Mediation analysis was used to evaluate the role of childhood growth, adulthood obesity, cardiometabolic diseases and blood biomarkers in mediating the birth weight-MI relationship. Linear regression was used to estimate associations of birth weight with left ventricular (LV) mass-to-volume ratio, LV stroke volume, global longitudinal strain, LV global function index and left atrial ejection fraction.
Results: 258 787 participants from white ethnicities (61% women, median age 56 (49, 62) years) were studied. Birth weight had a non-linear relationship with incident MI, with a significant inverse association below an optimal threshold of 3.2 kg (subdistribution HR: 1.15 (1.08 to 1.22), p=6.0×10-5) and attenuation to the null above this threshold. The birth weight-MI effect was mediated through hypertension (8.4%), glycated haemoglobin (7.0%), C reactive protein (6.4%), high-density lipoprotein (5.2%) and high cholesterol (4.1%). Birth weight-mortality associations were statistically non-significant after Bonferroni correction. In participants with cardiovascular magnetic resonance (n=19 314), lower birth weight was associated with adverse LV remodelling (greater concentricity, poorer function).
Conclusions: lower birth weight was associated with greater risk of incident MI and unhealthy LV phenotypes; effects were partially mediated through cardiometabolic disease and systemic inflammation. These findings support consideration of birth weight in risk prediction and highlight actionable areas for disease prevention.
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heartjnl-2022-321733.full
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Accepted/In Press date: 3 November 2022
e-pub ahead of print date: 16 November 2022
Published date: 16 November 2022
Additional Information:
Funding Information:
ZR-E recognises the National Institute for Health Research (NIHR) Integrated Academic Training Programme which supports her Academic Clinical Lectureship post and was supported by British Heart Foundation (BHF) Clinical Research Training Fellowship (FS/17/81/33318). SEP acknowledges support from the NIHR Biomedical Research Centre at Barts. SEP has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 825903 (euCanSHare Project). SEP acknowledges support from the 'SmartHeart' EPSRC Programme grant (www.nihr.ac.uk; EP/P001009/1). SN, CM and PL are supported by the Oxford NIHR Biomedical Research Centre and the Oxford BHF Centre of Research Excellence. SEP and SN acknowledge the BHF for funding the manual image analysis underpinning the creation of a cardiovascular MRI reference standard for the UK Biobank imaging resource in 5000 scans (www.bhf.org.uk; PG/14/89/31194). This project was enabled through access to the Medical Research Council (MRC) eMedLab Medical Bioinformatics infrastructure (www.mrc.ac.uk; MR/L016311/1). NH acknowledges support from MRC (MC_UU_12011/1) and NIHR Southampton Biomedical Research Centre. This work was supported by Health Data Research UK, an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities.
Publisher Copyright:
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Keywords:
Epidemiology, Magnetic Resonance Imaging, Risk Factors
Identifiers
Local EPrints ID: 472807
URI: http://eprints.soton.ac.uk/id/eprint/472807
ISSN: 1355-6037
PURE UUID: 73e501c8-74fa-4f9b-ae0f-70968ac34eb8
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Date deposited: 19 Dec 2022 17:45
Last modified: 17 Mar 2024 02:59
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Contributors
Author:
Zahra Raisi-Estabragh
Author:
Jackie Cooper
Author:
Mae S. Bethell
Author:
Celeste McCracken
Author:
Adam J. Lewandowski
Author:
Paul Leeson
Author:
Stefan Neubauer
Author:
Steffen E Petersen
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