Fatty acid–binding protein 4 and major adverse cardiovascular events: a dose–response meta-analysis of prospective cohort studies

AIMS: To quantify the association between circulating fatty acid-binding protein 4 (FABP4) levels and the risk of major adverse cardiovascular events (MACE) and secondary cardiovascular outcomes in prospective cohort studies. METHODS AND RESULTS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library from inception to 1 December 2025 for prospective cohort studies evaluating baseline FABP4 levels in relation to subsequent cardiovascular outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects models, and dose-response analyses were performed. Thirty-five prospective cohort studies were included (PROSPERO: CRD420261291090). In the pooled analysis, participants in the highest FABP4 category, as defined within each study, had a 61.6% higher risk of MACE than those in the lowest category (HR = 1.616, 95% CI: 1.402-1.863; I2 = 35.0%). This association remained significant when FABP4 was analysed as a continuous variable (HR = 1.393, 95% CI: 1.181-1.643; I2 = 79.9%). Higher FABP4 levels were also associated with higher risks of secondary cardiovascular outcomes, including cardiovascular death, heart failure, and myocardial infarction. In linear dose-response analyses, each 10 ng/mL higher baseline FABP4 level was associated with a 16.6% higher risk of MACE and a 13.1% higher risk of cardiovascular death, with no evidence of non-linearity. Sensitivity analyses yielded similar results, and no substantial publication bias was detected for the primary MACE analysis. CONCLUSION: Higher FABP4 levels were associated with higher risks of MACE and cardiovascular death, supporting its potential relevance as a prognostic marker warranting further evaluation.