The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study
The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study
Aims: we examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.
Methods and results: in 491606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity–outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.
Conclusions: we demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity–outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.
body mass index, cardiac magnetic resonance imaging, cardiovascular remodelling, disease mechanisms, incident cardiovascular outcomes, mediation, obesity, waist-to-hip ratio
921–929
Szabo, Liliana
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McCracken, Celeste
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Cooper, Jackie
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Rider, Oliver J.
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Vago, Hajnalka
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Merkely, Bela
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Harvey, Nicholas C.
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Neubauer, Stefan
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Petersen, Steffen E.
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Raisi-Estabragh, Zahra
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20 January 2023
Szabo, Liliana
a5da4e9d-450f-43e5-b2de-1b1cabde6a6c
McCracken, Celeste
5d772e9e-3aaa-41da-a5ef-3943b1631fd9
Cooper, Jackie
f78de577-4cac-496f-ad11-5f59dd305046
Rider, Oliver J.
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Vago, Hajnalka
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Merkely, Bela
e00fa145-1c09-496d-b62b-c1fe1ba5b037
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Neubauer, Stefan
c8a34156-a4ed-4dfe-97cb-4f47627d927d
Petersen, Steffen E.
04f2ce88-790d-48dc-baac-cbe0946dd928
Raisi-Estabragh, Zahra
43c85c5e-4574-476b-80d6-8fb1cdb3df0a
Szabo, Liliana, McCracken, Celeste, Cooper, Jackie, Rider, Oliver J., Vago, Hajnalka, Merkely, Bela, Harvey, Nicholas C., Neubauer, Stefan, Petersen, Steffen E. and Raisi-Estabragh, Zahra
(2023)
The role of obesity-related cardiovascular remodelling in mediating incident cardiovascular outcomes: a population-based observational study.
European Heart Journal, 24 (7), .
(doi:10.1093/ehjci/jeac270).
Abstract
Aims: we examined associations of obesity with incident cardiovascular outcomes and cardiovascular magnetic resonance (CMR) phenotypes, integrating information from body mass index (BMI) and waist-to-hip ratio (WHR). Then, we used multiple mediation to define the role of obesity-related cardiac remodelling in driving obesity-outcome associations, independent of cardiometabolic diseases.
Methods and results: in 491606 UK Biobank participants, using Cox proportional hazard models, greater obesity (higher WHR, higher BMI) was linked to significantly greater risk of incident ischaemic heart disease, atrial fibrillation (AF), heart failure (HF), all-cause mortality, and cardiovascular disease (CVD) mortality. In combined stratification by BMI and WHR thresholds, elevated WHR was associated with greater risk of adverse outcomes at any BMI level. Individuals with overweight BMI but normal WHR had weaker disease associations. In the subset of participants with CMR (n = 31 107), using linear regression, greater obesity was associated with higher left ventricular (LV) mass, greater LV concentricity, poorer LV systolic function, lower myocardial native T1, larger left atrial (LA) volumes, poorer LA function, and lower aortic distensibility. Of note, higher BMI was linked to higher, whilst greater WHR was linked to lower LV end-diastolic volume (LVEDV). In Cox models, greater LVEDV and LV mass (LVM) were linked to increased risk of CVD, most importantly HF and an increased LA maximal volume was the key predictive measure of new-onset AF. In multiple mediation analyses, hypertension and adverse LV remodelling (higher LVM, greater concentricity) were major independent mediators of the obesity–outcome associations. Atrial remodelling and native T1 were additional mediators in the associations of obesity with AF and HF, respectively.
Conclusions: we demonstrate associations of obesity with adverse cardiovascular phenotypes and their significant independent role in mediating obesity–outcome relationships. In addition, our findings support the integrated use of BMI and WHR to evaluate obesity-related cardiovascular risk.
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Accepted/In Press date: 1 December 2022
e-pub ahead of print date: 20 January 2023
Published date: 20 January 2023
Additional Information:
Funding Information: L.S. received funding from the European Association of Cardiovascular Imaging (EACVI Research Grant App000076437). Z.R.-E. recognizes the National Institute for Health Research (NIHR) Integrated Academic Training programme which supports her Academic Clinical Lectureship post and was also supported by British Heart Foundation Clinical Research Training Fellowship No. FS/17/81/33318. S.N. and C.M. were supported by the Oxford NIHR Biomedical Research Centre and S.N. by Oxford NIHR Biomedical Research Centre and the Oxford British Heart Foundation Centre of Research Excellence. O.J.R. received funding from a BHF Intermediate Clinical Fellowship FS/16/70/32157. S.E.P. acknowledges support from the ‘SmartHeart’ EPSRC programme grant ( www.nihr.ac.uk ; EP/P001009/1) and also from the CAP-AI programme, London's first AI enabling programme focused on stimulating growth in the capital's AI Sector. CAP-AI is led by Capital Enterprise in partnership with Barts Health NHS Trust and Digital Catapult and is funded by the European Regional Development Fund and Barts Charity. S.E.P. has also received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 825903 (euCanSHare project). S.E.P. and S.N. acknowledge the British Heart Foundation for funding the manual analysis to create a CMR imaging reference standard for the UK Biobank imaging-resource in 5000 CMR scans ( www.bhf.org.uk ; PG/14/89/31194). N.C.H. acknowledges support from MRC (MC_UU_12011/1) and NIHR Southampton Biomedical Research Centre. This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure, supported by the Medical Research Council ( www.mrc.ac.uk ; MR/L016311/1). The funders provided support in the form of salaries for authors as detailed above but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. H.V. and B.M. acknowledge funding from the project no. TKP2021-NKTA-46 with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-NKTA funding scheme.
Keywords:
body mass index, cardiac magnetic resonance imaging, cardiovascular remodelling, disease mechanisms, incident cardiovascular outcomes, mediation, obesity, waist-to-hip ratio
Identifiers
Local EPrints ID: 473489
URI: http://eprints.soton.ac.uk/id/eprint/473489
ISSN: 0195-668X
PURE UUID: 903ecf2d-6a28-49ab-bb53-9e07ff30c2ce
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Date deposited: 20 Jan 2023 17:48
Last modified: 17 Mar 2024 02:59
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Contributors
Author:
Liliana Szabo
Author:
Celeste McCracken
Author:
Jackie Cooper
Author:
Oliver J. Rider
Author:
Hajnalka Vago
Author:
Bela Merkely
Author:
Stefan Neubauer
Author:
Steffen E. Petersen
Author:
Zahra Raisi-Estabragh
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