Liver disease is a significant risk factor for cardiovascular outcomes - a UK Biobank study.
Roca-Fernandez A., Banerjee R., Thomaides-Brears H., Telford A., Sanyal A., Neubauer S., Nichols TE., Raman B., McCracken C., Petersen SE., Ntusi NA., Cuthbertson DJ., Lai M., Dennis A., Banerjee A.
BACKGROUND AND AIMS: 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) was associated with increased risk of major CVD events. METHODS: Liver disease activity (cT1) and fat (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 and stroke), and CVD hospitalisation and all-cause mortality. Liver blood biomarkers (AST, ALT, AST/ALT ratio, FIB4), general metabolism biomarkers (CRP, HbA1c, systolic blood pressure (SBP), total cholesterol), and demographics were also included. Subgroup analysis was conducted in those without metabolic syndrome (MetS, defined by at least 3 of: a large waist, high triglycerides, low HDL cholesterol, increased SBP, or elevated HbA1c). RESULTS: 33,616 participants (65 years, mean BMI 26kg/m2, mean HbA1c 35mmol/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 [HR(CI) 1.14(1.03-1.26), p=0.008], AF [1.30 (1.12-1.5), p<0.001]; HF [1.30 (1.08 - 1.58), p=0.004]; CVD hospitalisation [1.27(1.18-1.387, p<0.001] and all-cause mortality [1.19(1.02-1.38), p=0.026]. FIB4 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 MetS [1.26(1.13-1.4), p<0.001]. CONCLUSION: Liver disease activity, by cT1, was independently associated with higher risk of incident CVD and all-cause mortality, independent of pre-existing metabolic syndrome, liver fibrosis or fat. IMPACT AND IMPLICATIONS: Chronic liver disease(CLD) is associated with two-fold greater incidence of cardiovascular disease(CVD). Our work shows that early liver disease on cardiac MRI (by cT1) was associated with higher risk of major CVD(14%), CVD hospitalisation(27%) and all-cause mortality(19%). Whether for patients, carers, clinicians, and policymakers, there are implications for early prevention of CLD and CVD.