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.