Abstract 4138472: Bioactive Oxylipins Predict Coronary Artery Calcification Severity in Heart Failure with Preserved Ejection Fraction

Background: Inflammation is a common underlying cause in atherosclerosis and heart failure with preserved ejection fraction (HFpEF). Recent data have highlighted the critical role of circulating bioactive polyunsaturated fatty acid oxidized lipids, or oxylipins, in initiating and resolving inflammation. We sought to study the role of oxylipins in predicting coronary artery calcification (CAC) in HFpEF. Hypothesis: We hypothesize that oxylipins can predict and distinguish CAC severity in HFpEF patients. Methods: We collected venous blood samples during right heart catheterization from 71 HFpEF patients. We categorized patients by CT-based CAC severity: none (control; n=16), mild (<25% CAC, n=7), moderate (26-50% CAC, n=22), and severe (>50% CAC, n=26). We measured 143 oxylipins in all study participants using mass spectrometry. Along with unpaired T-tests, machine learning analysis was used to determine lipid permutation importance and evaluate predictive accuracy for CAC severity. Results: Demographic variables showed no significant differences between groups. Increased total cholesterol (p=0.031) and low HDL (p=0.011) were associated with CAC severity. Pro-inflammatory 12(S)-HHTrE (a degradation product of TxA2) levels were elevated in severe CAC vs control (p=0.031). The inactivated anti-inflammatory 5,6 DiHETrE levels were higher in moderate CAC vs control (p=0.032) and severe CAC vs control (p=0.021). Out of 143 oxylipins, the panel of LTB5, 11(R)-HEDE, 20-HETE, 5-HEPE, 11(12)-EpETrE, 14(15)-EpETE, 19,20-DiHDoPE, PD1, and 5-oxoETE were the most significant predictors of severe vs non-severe (none, mild, moderate) CAC, with 88.88% predictive accuracy. Conclusion: In HFpEF patients, CAC severity can be predicted by a novel panel of circulating, bioactive venous oxylipins.