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May 13, 2026Metabolomics0 citationsOpen Access

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

AYAshish YadavSMSareeta ManandharAKAlex Kloster

Key Result

Obesity in patients with heart failure with preserved ejection fraction is associated with reduced arterialized oxylipin diols, including 12,13-DiHOME (OR 0.48), and higher PGE1 metabolites.

Key Points

  • The study aims to assess the association between obesity and oxylipins in patients with heart failure with preserved ejection fraction.
  • Prospective single-center cohort study involving 90 HFpEF patients.
  • Patients underwent transthoracic echocardiography and right heart catheterization with blood sampling.
  • Oxylipin levels were quantified using liquid chromatography-mass spectrometry and analyzed with logistic regression.
  • Obese patients showed lower levels of several arterialized oxylipins, including 12,13-DiHOME (OR:0.48; p=0.03) and 5(S),6(S)-DiHETE (OR:0.51; p=0.02).
  • Arterialized 19R-hydroxy-prostaglandin E1 was positively associated with obesity (OR:1.91; p=0.03).
  • Higher proportion of obese patients had pre- and post-capillary pulmonary hypertension (p=0.003).

Study Design

Type

Cohort (n=90)

Multicenter

No

Structured PICO

Is obesity associated with distinct arterialized and venous oxylipin profiles in patients with HFpEF?

P
Population
90 patients with heart failure with preserved ejection fraction (HFpEF)
I
Intervention
Obesity (BMI ≥ 30 kg/m²)
C
Comparator
Non-obese (BMI < 30 kg/m²)
O
Outcome
Association between obesity and arterialized and venous oxylipinssurrogate

Obesity in HFpEF is associated with a distinct oxylipin profile, including reduced oxylipin diols and higher prostaglandin E1 metabolites, which may contribute to the pathophysiology of the disease.

Main Result

Effect estimate: OR 0.48 (95% CI 0.24-0.92)

p-value: p=0.03

Limitations

  • Small sample size of 90 patients limits statistical power
  • Binary categorization of obesity precluded analysis of overweight patients as a distinct intermediate phenotype
  • Limited covariates in multivariable model due to sample size
  • Prolonged storage of samples may introduce variability in the measurement of less stable oxylipin species
  • Cohort recruited before routine use of modern HFpEF therapies like SGLT-2 inhibitors
  • Lack of a non-HFpEF control group or HFrEF comparator cohort
  • Cross-sectional design limits inference regarding causality
  • Reliance on BMI as sole metric of obesity limits ability to account for adipose tissue distribution
  • No statistical corrections for multiple testing

Abstract

Abstract 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. Graphical abstract

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Cite This Study

Yadav et al. (2026) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF) (n=90). Obesity (BMI ≥ 30 kg/m²) vs. Non-obese (BMI < 30 kg/m²) was evaluated on Association of obesity with arterialized 12,13-DiHOME (OR 0.48, 95% CI 0.24-0.92, p=0.03). Obesity in patients with heart failure with preserved ejection fraction is associated with reduced arterialized oxylipin diols, including 12,13-DiHOME (OR 0.48), and higher PGE1 metabolites.

synapsesocial.com/papers/6a04153d79e20c90b444514ahttps://doi.org/10.1007/s11306-026-02449-x
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