Abstract Body (Do not enter title and authors here): Background
Circulating acylcarnitines (ACs), biomarkers of mitochondrial β-oxidative function, are linked to cardiovascular diseases (CVD) yet the extent to which ACs relate to prospective cardiac aging remains uncertain. We investigate the longitudinal associations between ACs, cardiac function, and clinical outcomes.

Methods
A population-based sample of community older adults without CVD underwent baseline serum metabolomic profiling and interval echocardiography at five years. Incident hospitalizations were prospectively tracked from 2014 to 2021. Multiple linear regression adjusted for significant clinical variables.

Results
Of 202 participants (baseline 65±11.9 years, 49.3% women), we observed interval increases in risk factors (hypertension 39% vs 52.2% p<0.001; dyslipidemia 39% vs 50% p=0.034; diabetes 11.7% vs 18.8% p=0.035; smoking 13.2% vs 24.7% p=0.003; waist circumference 81±10.1 vs 86±9.9cm p<0.001) during follow-up (4.9±0.4 years). These changes paralleled E/e’ increases (8.9±2.6 vs 11.1±3.3 p<0.001) and E/A decreases (1.09±0.4 vs 1.0±0.4 p<0.001). Baseline C8:1 (β=0.182 p=0.011), C22:3 (β=0.148 p=0.047), C22:5 (β=0.210 p=0.003), C5:1 (β=-0.142 p=0.048), and C16-OH (β=-0.156 p=0.028) levels were associated with E/e’ change over time while C6 (β=0.163 adj. p=0.019), C8:1 (β=0.137 adj. p=0.047), C10:2 (β=0.153 adj. p=0.035), C14:3 (β=0.147 adj. p=0.031), and C16:1-OH/C14:1-DC (β=0.158 adj. p=0.022) were associated with E/A change. At follow-up, baseline C8:1 (β=0.178 adj. p=0.006) and C10:3 (β=0.145 adj. p=0.024) were associated with E/e’ while C4-DC/C6-OH (β=-0.004 adj. p=0.034) was associated with E/A. Baseline C22:2 predicted incident hospitalizations (HR=1.20 95%CI 1.03-1.39, adj. p=0.018).

Conclusion
Circulating ACs independently predicted declining cardiac function and adverse outcomes over five years among older adults without CVD. The prognostic effect of ACs should be translated to strategies targeting mitochondrial health in cardiac aging prevention.