Beyond the Liver: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) Associated 35% Higher Risk of Clinically Diagnosed Heart Failure With Preserved Ejection Fraction (HFpEF)

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), shares pathophysiological links with heart failure with preserved ejection fraction (HFpEF), but their clinical association remains underexplored. OBJECTIVE: This systematic review and meta-analysis evaluates the association between MASLD and clinically diagnosed HFpEF and trying to quantify the magnitude of this association across available clinical studies. METHODS: This review was registered on PROSPERO (CRD42025644064), we systematically searched PubMed, Embase, and Scopus (from inception to February 2025) for studies reporting clinical HFpEF prevalence in MASLD versus non-MASLD cohorts, using the following search terms: ("metabolic associated fatty liver disease" OR "MAFLD" OR "metabolic dysfunction associated steatotic liver disease" OR "MASLD" OR "non-alcoholic fatty liver disease" OR "NAFLD") AND ("heart failure with preserved ejection fraction" OR "HFpEF" OR "diastolic heart failure" OR "preserved ejection fraction") Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in R using "Meta" package by both Mantel-Haenszel (common effects) and Inverse variance (random effects) methods. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for observational studies. RESULTS: We identified 3313 publications from electronic and hand-searches, two reviewers independently screened studies and extracted data following PRISMA guidelines. After excluding studies failing to meet our inclusion criteria of comparing MASLD vs. non-MASLD regarding the occurrence/prevalence of HFpEF as a clinical diagnosis, and duplicates,123 full-text studies were assessed for eligibility, of these, 3 studies (n = 899,629; 47,610 MASLD patients), two cohorts-studies and one cross-sectional study were included in the analysis. The HFpEF prevalence was 2.2% among the MASLD group versus1.85% in the non-MASLD group. MASLD was significantly associated with increased HFpEF risk (pooled OR 1.35, 95% CI 1.26-1.45; *p*<0.0001), representing an absolute risk increase of 0.35%. Statistical heterogeneity was negligible across studies (I² = 0.0%, τ² = 0, Q = 0.90, p = 0.6365). CONCLUSION: Based on evidence base of three eligible studies, MASLD appears to independently increase the risk of clinically diagnosed HFpEF by 35%, with advanced fibrosis conferring additional risk; these findings should be regarded as hypothesis-generating. These finding support implementing integrated cardiovascular screening protocols in MASLD patients, particularly those with advanced fibrosis or metabolic comorbidities, and exploring therapeutic strategies targeting shared metabolic pathways (e.g., GLP-1 agonists) are warranted.