Liver and Bile
J Hepatol. 2023;79(5):1085–95
Liver disease is a significant risk factor for cardiovascular outcomes – A UK Biobank study
Background and aims: Chronic liver disease (CLD) is associated with increased cardiovascular disease (CVD) risk. This study investigated whether early signs of liver disease (measured by iron-corrected T1-mapping [cT1]) were associated with an increased risk of major CVD events.
Methods: 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 substudy. Using multivariable Cox regression, the authors explored associations between liver cT1 (magnetic resonance imaging, MRI) and primary CVD (coronary artery disease, atrial fibrillation [AF], embolism/vascular events, heart failure [HF] and stroke), and CVD hospitalization 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 3 of: a large waist, high triglycerides, low high-density lipoprotein cholesterol, increased systolic blood pressure, or elevated hemoglobin A1c).
Results: A total of 33,616 participants (mean age, 65 years, mean BMI 26 kg/m2, mean hemoglobin 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 [HR] = 1.14; 95% confidence interval [CI]: 1.03–1.26; p = 0.008), AF (HR = 1.30; 95% CI: 1.12–1.51; p < 0.001), HF (HR = 1.30; 95% CI: 1.09–1.56; p = 0.004), CVD hospitalization (HR = 1.27; 95% CI: 1.18–1.37; p < 0.001) and all-cause mortality (HR = 1.19; 95% CI: 1.02–1.38; p = 0.026). Fibrosis-4 index was associated with HF (HR = 1.06; 95% CI: 1.01–1.10; p = 0.007). Risk of CVD hospitalization was independently associated with cT1 in individuals without metabolic syndrome (HR = 1.26; 95% CI: 1.13–1.4; p < 0.001).
Conclusion: Liver disease activity, by iron-corrected T1-mapping, was independently associated with a higher risk of incident cardiovascular disease and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat.