Obesity is associated with distinct oxylipins in heart failure with preserved ejection fraction

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of heart failure cases, with obesity emerging as a key pathophysiologic driver. Oxylipins are lipid signaling molecules linked to adverse HFpEF outcomes, but their relationship with obesity remains unclear. OBJECTIVES: To evaluate association between obesity and arterialized and venous oxylipins in HFpEF patients. METHODS: In this prospective single-center cohort study, 90 patients with HFpEF underwent transthoracic echocardiography and right heart catheterization with arterialized pulmonary capillary and venous blood sampling. Serum oxylipins were quantified via liquid chromatography-mass spectrometry. Oxylipin levels were log-transformed and standardized. Oxylipin associations with obesity (BMI ≥ 30 kg/m²) were evaluated using logistic regression, and pulmonary hypertension (PH) subgroup analyses using a one-sample proportion test. RESULTS: Of the 90 patients, 61 (67.8%) were obese. Obese patients were younger, more frequently female and African American, had higher prevalence of diabetes (54.1% vs. 17.2%, p < 0.001) and exhibited greater interventricular septal and posterior wall thickness. Multivariable and volcano plot analyses demonstrated inverse associations between obesity and several arterialized oxylipins, including 12,13-DiHOME (OR:0.48; p = 0.03), 19,20-DiHDoPE (OR:0.53; p = 0.03), 11,12-DiHETrE (OR:0.31, p = 0.04), 9,10-DiHOME (OR;0.42; p = 0.02), and 5(S),6(S)-DiHETE (OR:0.51; p = 0.02). In contrast, arterialized 19R-hydroxy-prostaglandin E1 was positively associated with obesity (OR:1.91, p = 0.03). Among venous oxylipins, 15(R)-PGE1 (OR:2.23; p = 0.02) and 19R-hydroxy-prostaglandin E1 (OR:1.91; p = 0.02) showed positive associations with obesity. Obese patients constituted a higher proportion of combined pre- and post-capillary PH subgroup (p = 0.003). CONCLUSIONS: Obesity in HFpEF is associated with reduced oxylipin diol levels, higher levels of prostaglandin E1 metabolites, and higher burden of pulmonary hypertension.