Abstract P259: Favorable Ventricular-Arterial Mechanics Among Women is Associated With Better Mitochondrial Oxidation in the Left Ventricle

Background: Traditional risk factors insufficiently characterize the biological phenomena underlying sex differences in ventriculoarterial coupling (VAC). We hypothesize that sex differences in VAC are due to differences in left ventricular global longitudinal strain (LVGLS), a fuel-dependent chamber closely linked to mitochondrial fuel oxidation pathways. Methods: Community older adults without cardiovascular disease were prospectively recruited for cardiac magnetic resonance imaging and concurrent serum metabolomics sampling. VAC was determined as aortic pulse wave velocity (PWV) divided by LVGLS. Multivariable models adjusted for clinical risk factors and metabolites. Results: Among 202 participants (46.0% female), fewer women were smokers compared to men (3.2% vs 25.7% p<0.001). Despite similarities in age, (women: 69.7 vs men: 70.7 p=0.432) women had better VAC (-0.39 vs -0.47 p = 0.003), LVGLS (-21.9 vs -20.1% p <0.001), and LV mass index (LVMI) (41.7 vs 49.5 g/m 2 p <0.001) compared to men. Both sexes had similar PWV (8.41 vs 9.13 m/s p = 0.087). LVGLS was inversely related to LVMI (β = -0.09 p <0.001). Among women, metabolomic determinants of better LVGLS, independent of LVMI, were lower levels of long chain acylcarnitines (LCACs) C12:2-OH/C10:2-DC (OR 0.830 adj. p=0.020), C16:3-OH/C14:3-DC (OR 0.334 adj. p=0.048), C16-OH (OR 0.756 adj. p=0.029) and higher levels of C20:2 (OR 1.987 adj. p=0.033) (Figure A). Among men, determinants of better LVGLS included lower levels of C12:2-OH/C10:2-DC (OR 0.864 adj. p=0.020), C12:1-OH (OR 0.969 adj. p=0.016), C16:1 (OR 0.923 adj. p=0.025), C16:3-OH/C14:3-DC (OR 0.566 adj. p=0.028)] and higher levels of C5:1 (OR 1.096 adj. p=0.026). Conclusion: Better LV longitudinal function contributed to better VAC among older women. Lower LCAC fatty acid metabolism intermediaries was linked to better LVGLS, implying improved mitochondrial β-oxidation. Circulating metabolites may represent novel precision medicine factors for sex-based stratification of vascular risks.