NAFLD Raises Risk of Incident Heart Failure with Increased Risk as Disease Worsens

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A diagnosis of nonalcoholic fatty liver disease (NAFLD) was linked to a moderate 1.5-fold greater risk for incident heart failure (HF) in the next decade with risk increasing linearly with NAFLD disease severity, reports a team of Italian researchers. Their findings, published in the journal Gut, are based on a meta-analysis that comprised data from more than 11 million individuals.

“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.”

As context for their research, investigators led by Giovanni Targher, MD, assistant professor of endocrinology and diabetes at the University of Verona Medical School, Verona, Italy, cite the association between NAFLD and increased risk of new-onset HF reported in recent studies but the paucity of data on whether the risk is affected by severity of liver disease.

To help build the body of evidence, Targher et al performed a meta-analysis of longitudinal cohort studies identified during a systematic search of the SCOPUS, Web of Science, and PubMed databases from database inception through March 2022.

Studies eligible for inclusion in the meta-analysis were required to examine risk of new-onset HF events in adults with or without NAFLD. NAFLD was diagnosed by serum biomarkers/scores, ICD codes, imaging, or hepatic histology. The investigators’ primary outcome of interest was the risk of new-onset HF among those with NAFLD vs participants without NAFLD. HF diagnosis was based primarily on ICD-9 or ICD-10 codes, according to the study.

FINDINGS

Final eligible studies for analysis numbered 11 with data from 11 242 231 middle-aged adults with international representation. Mean age of participants was 55 years and 50.1% were women. Mean BMI was 26.

During a median follow-up of 10 years the researchers identified 97 716 cases of incident HF. They found that the presence of NAFLD was associated with a 50% greater risk of new-onset HF (HR 1.50, 95% CI 1.34-1.67, P <.001). Importantly they determined that the risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension, and other common cardiovascular risk factors.

They also found that risk of incident HF appeared to increase with the severity of NAFLD and particularly among those with more extensive liver fibrosis (HR 1.76, 95% CI 0.75-4.36). This finding, however, was based on only 2 studies.

“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 wrote. They call for “high-quality prospective and mechanistic studies” to help clarify what proves to be a complex link between NAFLD and risk of new-onset HF. Future research also should explore “whether genetic polymorphisms that increase risk of NAFLD can modify risk of heart failure and test whether resolution or improvement of NAFLD may reduce risk of new-onset heart failure.”

The research team acknowledges several study limitations including potential unmeasured and residual confounding as well as the observational design of the studies included.

Reference: Mantovani A, Petracca G, Csermely A, et al. Non-alcoholic fatty liver disease and risk of new onset heart failure: an updated meta-analysis of about 11 million individuals. Gut 2022; doi:10.1136/gutjnl-2022-327672.