Abstract Body (Do not enter title and authors here): Background
Superior left ventricular (LV) systolic function among older women over men has been linked to differences in aging-related ventricular remodeling. Global longitudinal strain (LVGLS) is particularly susceptible to early aging perturbations and may precede systolic failure. Combining cardiovascular magnetic resonance (CMR) with metabolomics, we investigated LVGLS in parallel with markers of myocardial biosynthesis and metabolism pathways to explore the mechanisms and sex dimorphisms of cardiac aging.

Methods
Community adults without cardiovascular disease (CVD) underwent serum metabolomics profiling and simultaneous CMR. Prospective clinical outcomes were tracked from 2014 to 2021. Multiple logistic regression adjusted for significant baseline variables.

Results
Among 202 participants (46% women, 70.2±8.8 years), participants with better LVGLS were characterized by smaller LV chambers (LVESVi 30.0±14.2 vs 22.0±5.6ml/m², adj. p <0.001; LVEDVi 70.9±19.9 vs 64.0±10.2ml/m², p=0.001 adj. p=0.054) and mass (LVMi 51.5±14.5 vs 43.9±8.8g/m², adj. p=0.008) accompanied by lower levels of several long-chain acylcarnitines species (C12:2-OH/C10:2-DC, C12:1-OH, C12-OH/C10-DC, C14, C16:3-OH/C14:3-DC) independent of sex, diastolic blood pressure, smoking history, and body habitus. Compared to men of similar age, women had superior LVGLS (-21.9±2.6 vs -20.1±2.8%, adj. p=0.024) in tandem with smaller ventricles and less hypertrophy despite similar adjusted LVEF. Higher anaplerotic (methionine, arginine) and proteogenic (phenylalanine, tyrosine) amino acids (AA), together with lower acylcarnitines, distinguished women with better over poorer LVGLS while no AA differences were observed among men. During follow-up, poorer baseline LVGLS was associated with incident composite mortality and hospitalizations (OR=1.12 95%CI 1.01-1.24, p=0.026 adj. p=0.049).

Conclusion
Preserved ventricular systolic function among older women was linked to superior LVGLS and favorable remodeling than men. Better LVGLS was accompanied by biomarkers of better mitochondrial oxidation, anaplerosis, and proteogenesis, suggesting enhanced myocardial fuel energetics and biosynthesis with better strain. LVGLS represents a promising quantifiable marker of early systolic aging among older adults without CVD linked to prospective clinical outcomes. Biological insights into the aging-adaptive mechanisms of strain conservation may reveal targets in preventing aging susceptibilities to myocardial dysfunction.