Circulating mediators linking cardiometabolic diseases to HFpEF: a mediation Mendelian randomization analysis

These findings suggest that metabolic HFpEF has distinct etiological features compared with HFrEF and is driven by complex, condition-specific mediators. IL1R1 mediates HFpEF in multiple metabolic risk states, suggesting a potential therapeutic target. Further translational studies are warranted to evaluate anti-inflammatory strategies targeting IL1R1 in HFpEF.