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

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. 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. 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. 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). 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.