Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study.



Roca-Fernandez, Adriana, Banerjee, Rajarshi, Thomaides-Brears, Helena, Telford, Alison ORCID: 0000-0002-3712-0060, Sanyal, Arun, Neubauer, Stefan, Nichols, Thomas E ORCID: 0000-0002-4516-5103, Raman, Betty ORCID: 0000-0002-1239-9608, McCracken, Celeste, Petersen, Steffen E ORCID: 0000-0003-4622-5160
et al (show 5 more authors) (2023) Liver disease is a significant risk factor for cardiovascular outcomes - A UK Biobank study. Journal of hepatology, 79 (5). pp. 1085-1095.

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Abstract

<h4>Background & aims</h4>Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. We investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.<h4>Methods</h4>Liver disease activity (cT1) and fat (proton density fat fraction [PDFF]) were measured using LiverMultiScan® between January 2016 and February 2020 in the UK Biobank imaging sub-study. Using multivariable Cox regression, we explored associations between liver cT1 (MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers, general metabolism biomarkers, and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (defined as at least three of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated haemoglobin A1c).<h4>Results</h4>A total of 33,616 participants (mean age 65 years, mean BMI 26 kg/m<sup>2</sup>, mean haemoglobin A1c 35 mmol/mol) had complete MRI liver data with linked clinical outcomes (median time to major CVD event onset: 1.4 years [range: 0.002-5.1]; follow-up: 2.5 years [range: 1.1-5.2]). Liver disease activity (cT1), but not liver fat (PDFF), was associated with higher risk of any major CVD event (hazard ratio 1.14; 95% CI 1.03-1.26; p = 0.008), AF (1.30; 1.12-1.51; p <0.001); HF (1.30; 1.09-1.56; p= 0.004); CVD hospitalisation (1.27; 1.18-1.37; p <0.001) and all-cause mortality (1.19; 1.02-1.38; p = 0.026). FIB-4 index was associated with HF (1.06; 1.01-1.10; p = 0.007). Risk of CVD hospitalisation was independently associated with cT1 in individuals without metabolic syndrome (1.26; 1.13-1.4; p <0.001).<h4>Conclusion</h4>Liver disease activity, by cT1, was independently associated with a higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.<h4>Impact and implications</h4>Chronic liver disease (CLD) is associated with a twofold greater incidence of cardiovascular disease. Our work shows that early liver disease on iron-corrected T1 mapping was associated with a higher risk of major cardiovascular disease (14%), cardiovascular disease hospitalisation (27%) and all-cause mortality (19%). These findings highlight the prognostic relevance of a comprehensive evaluation of liver health in populations at risk of CVD and/or CLD, even in the absence of clinical manifestations or metabolic syndrome, when there is an opportunity to modify/address risk factors and prevent disease progression. As such, they are relevant to patients, carers, clinicians, and policymakers.

Item Type: Article
Uncontrolled Keywords: Humans, Digestive System Diseases, Liver Diseases, Cardiovascular Diseases, Iron, Risk Factors, Aged, Biological Specimen Banks, Biomarkers, Metabolic Syndrome, Glycated Hemoglobin, UK Biobank
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 13 Oct 2023 10:23
Last Modified: 16 Mar 2024 07:05
DOI: 10.1016/j.jhep.2023.05.046
Open Access URL: https://doi.org/10.1016/j.jhep.2023.05.046
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3173690