Abstract 4138498: Sex Differences in Plasma Acylcarnitines in Patients with STEMI undergoing Primary PCI

Background: Rapid coronary reperfusion using primary PCI is the corner stone therapy for patients presenting with STEMI that restores blood flow and limits infarct size. But paradoxically, the reperfusion process itself can induce additional myocardial injury. Females have increased rates of cardiovascular death compared with males following MI, and it is unclear whether this is related to differences in presentation or reperfusion injury. Given these differences, we aim to better understand the sex differences in the lipidome shift post PCI. METHODS&RESULTS: 126 patients(97 males, 29 females) undergoing PCI for STEMI in a tertiary centre underwent venous blood sampling and semi-targeted Liquid Chromatography Tandem Mass Spectrometry(LC/MS/MS) to determine 291 lipid species. Samples were taken pre-PCI(T0), and 2 hours post PCI(T1) with successful reperfusion. Each lipid class and species were compared between males and females at each time point using statistical analysis, to determine the similarities and differences in plasma lipidome shifts in ACS between sexes. Whilst most lipid classes decrease following reperfusion in STEMI (T0 vs T1), Acylcarnitines increase (20%, adjusted p=0.003) in both sexes. There is a clear sex difference with a greater increase in females (39% increase, adjusted p=0.03), as compared with males (13% increase, adjusted p=0.048). In both sexes this is primarily driven by OctadecanoylCarnitine (C8), which is a medium-chained acylcarnitine. Notably, there was no significant difference in C8 between the sexes in the control group, nor the pre-PCI group(adjusted p=0.48, at T0). At T0, total free fatty acids(FFA) and total phosphatidylinositol were significantly elevated in females compared with males(adjusted p=0.012, p=0.018 respectively). Conclusion: Our analysis suggests there are differences in lipidomics shift between males and females in response to myocardial reperfusion. The higher levels of circulating FFA in ischemic females pre-PCI(T0), followed by a parallel increase of acylcarnitine with reperfusion(T0vsT1), suggest differences between the sexes in myocardial metabolic response to reperfusion injury. C8 has been associated with elevated risk of cardiovascular death in stable CAD, but its clinical impact during reperfusion is still unknown. Detailed understanding of sex specific lipidomics shifts during reperfusion injury will allow us to better understand the mechanistic differences in clinical outcome between males and females.