Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals

Abstract

ObjectiveRecent studies reported an association between non-alcoholic fatty liver disease (NAFLD) and increased risk of new-onset heart failure (HF). However, the magnitude of the risk and whether this risk changes with severity of liver disease remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of new-onset HF.DesignWe systematically searched Scopus, Web of Science and PubMed from database inception to March 2022 to identify eligible observational studies, in which NAFLD was diagnosed by serum biomarkers/scores, International Classification of Diseases (ICD) codes, imaging techniques or liver histology. The primary outcome was new-onset HF, as assessed mainly by ICD codes. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs.ResultsWe identified 11 longitudinal cohort studies with aggregate data on 11 242 231 middle-aged individuals from different countries and 97 716 cases of incident HF over a median of 10 years. NAFLD was associated with a moderately higher risk of new-onset HF (pooled random-effects hazard ratio 1.50, 95% CI 1.34 to 1.67, p<0.0001; I2=94.8%). This risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension and other common cardiovascular risk factors. Sensitivity analyses did not change these results. The funnel plot did not show any significant publication bias.ConclusionNAFLD is associated with a 1.5-fold higher long-term risk of new-onset HF, regardless of the presence of diabetes, hypertension and other common cardiovascular risk factors. However, the observational design of the studies does not allow for proving causality.

Fatty liver disease, heart rate and cardiac remodelling: Evidence from the UK Biobank

“…There has been a debate whether the association between FLD and CVD is mediated by residual confounding cardiovascular risk factors associated with metabolic syndrome. However, more recent data suggest that FLD is not only associated with an increased risk of CVD but also independently increases the risk of cardiovascular events, including stroke, congestive heart failure and cardiovascular mortality 4–7 …”

Association between nonalcoholic fatty liver disease and atrial fibrillation and other clinical outcomes: a meta-analysis

“…37 The event of new-onset HF was reported to be 1.5 times higher in patients diagnosed with NAFLD compared to healthy liver controls in a recent systematic review, but observational studies that were analyzed were unable to establish a direct causality. 38 HF and AF are well-reported risk factors in the literature that have direct correlations with the progression of fibrosis in the NAFLD patients with or without atherosclerotic history. 39,40 As such, it is unique to note that CVM is an extremely variable outcome in the literature with studies citing no differences and other advocating mortality to be significantly increased in NAFLD.…”

The regulatory role of metabolic organ-secreted factors in the nonalcoholic fatty liver disease and cardiovascular disease

“…Moreover, there was a strong association between NAFLD and increased risk of new-onset HF, and this risk increased with the severity of NAFLD, especially in the fibrotic stage ( 134 ). A meta-analysis of 11 longitudinal cohort studies with a median follow-up of 10 years disclosed that NAFLD was associated with a 1.5-fold increased risk of new-onset HF, regardless of the presence of diabetes, hypertension, adiposity and other common cardiovascular risk factors ( 135 ). Simultaneously, in-hospital mortality of primary HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) was higher in patients with NAFLD compared with those without NAFLD ( 136 ).…”