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NAFLD Linked to Increased Risk of New-Onset Heart Failure

A systematic review and meta-analysis of 11 longitudinal cohort studies containing more than 11 million patients suggest presence of NAFLD was associated with a 1.5-fold increase in risk of new-onset heart failure in adjusted models.

Results of a review of available data within multiple databases are providing clinicians with further insight into the relationship between nonalcoholic fatty liver disease (NAFLD) and risk of new-onset heart failure.

A common comorbidity among patients with type 2 diabetes, results of the study suggest a diagnosis of NAFLD was associated with a 1.5-fold greater risk in developing incident heart failure in the next decade in adjusted models and with this risk growing further as disease severity of NAFLD increases.

“The results of this large and updated meta-analysis provide evidence that NAFLD is moderately associated with a higher risk of new-onset heart failure over a median follow-up of 10 years,” wrote investigators. “Importantly, the increase in risk of new-onset HF with NAFLD is independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other risk factors. Our data also suggest that the magnitude of this increase in risk seems to parallel the severity of NAFLD, especially the severity of liver fibrosis.”

With the prevalence of NAFLD and societal burden of heart failure continuing to increase, investigators designed the current study with the intent of providing fellow clinicians with an overview of the association observed between the conditions using longitudinal data from studies identified within the Scopus, Web of Science, and PubMed databases published from inception through March 2022. Through their search, Investigators identified 11 longitudinal cohort studies with data from 11,242,231 individuals aged for inclusion in their systematic review and meta-analysis.

To be eligible for inclusion in the current study, publications needed to examine risk of new-onset heart failure events in adult patients with or without NAFLD. Initially, the investigators' search returned 490 records and each study was assessed for quality using the Newcastle-Ottawa Scale. The investigators’ primary outcome of interest was risk of developing new-onset heart failure among those with NAFLD compared to the NAFLD-free controls. Of note, investigators pointed out ascertainment of incident heart failure outcomes was based mainly on ICD-9 or ICD-10 codes.

Over a median follow-up of 10 years, 97,716 cases of incident heart failure were identified over the 11,242,231 individuals included in the systematic review and meta-analysis. Upon analysis, results indicated presence of NAFLD was associated with a moderately greater risk of new-onset heart failure (HR, 1.50 [955 CI, 1.34-1.67]; P <.0001, I2=94.8%), with this risk independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other common cardiovascular risk factors. In sensitivity analyses, results demonstrated those with more advanced NAFLD had an even greater risk of heart failure, with studies assessing fibrosis biomarkers indicating those with fibrosis experienced even greater increases in risk of new-onset heart failure (HR, 1.76 [95% CI, 0.75-4.36]; I2=96.9%)

“We believe that the results of our meta-analysis further highlight the need for a patient-centered, multidisciplinary and holistic approach to manage both liver disease and cardiovascular risk in people with NAFLD,” investigators added. “Future high-quality prospective and mechanistic studies are certainly needed to better elucidate the existing but complex link between NAFLD and risk of new-onset heart failure; to examine whether genetic polymorphisms that increase risk of NAFLD can modify risk of heart failure and to test whether resolution or improvement of NAFLD may reduce risk of new-onset heart failure.”

This study, “Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals,” was published in Gut.