Abstract 4140688: Bioactive Oxylipins Predict Aortic Vascular Calcification Severity in Heart Failure with Preserved Ejection Fraction

Background: Aortic calcification has been significantly linked to the development of heart failure with preserved ejection fraction (HFpEF). Both HFpEF and aortic calcification are associated with inflammation, vascular dysfunction, and remodeling. Circulating polyunsaturated fatty acid oxidized lipids, or oxylipins, have been well described to initiate and resolve inflammation in cardiovascular disease. We questioned the role of these bioactive oxylipins in predicting aortic vascular calcification severity in HFpEF. Hypothesis: We hypothesize that oxylipins can predict and distinguish aortic vascular calcification severity in HFpEF patients. Methods: We collected venous blood samples during right heart catheterization from 57 HFpEF patients. We categorized patients by CT-based aortic vascular calcification severity: none (control; n=8), mild (<25%, n=14), moderate (26-50%, n=9), and severe (>50%, 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 oxylipin permutation importance and evaluate predictive accuracy for aortic vascular calcification severity. Results: Demographic variables showed no significant differences between groups. Pro-inflammatory TXB2 levels were elevated in severe aortic calcification vs control (p=0.036). This is further substantiated by increased 12(S)-HHTrE (a degradation product of TXA2) levels in severe aortic calcification vs control (p=0.0266). Anti-inflammatory 7(8)-EpDPE was also elevated in severe aortic calcification compared to control (p=0.0067). Finally, the inactivated anti-inflammatory 5,6 DiHETrE levels were higher in severe aortic calcification vs control (p=0.019). Out of 143 oxylipins, the 12-lipid panel of 5(S),15(S)-DiHETE, 5,6-DiHETrE, PGE2, 4-HDoHE, 15-keto PGE2, 11dh-2,3-dinor TXB2, iPF-VI, 19,20-DiHDoPE, 9(S)-HOTrE, 13,14dh-15k-PGE2, 5-oxoETE, and PD1 were the most significant predictors of severe (n=26) vs non-severe (none, mild, moderate; n=31) aortic vascular calcification, with 100% predictive accuracy. Conclusion: In HFpEF patients, aortic vascular calcification severity can be predicted with remarkable accuracy by a novel panel of circulating, bioactive venous oxylipins.