Among 657 patients undergoing elective vascular surgery over a decade, high circulating fatty acid synthase (cFAS) independently predicted 5-year major adverse events (aHR 1.94), mortality (aHR 1.77), major adverse limb events (aHR 4.53), and reintervention (aHR 2.50). Severe frailty (mFI-5 ≥ 3) predicted cardiovascular events (aHR 2.69) and overall major adverse events but not limb-specific endpoints. Critically, combining both biomarkers raised the 1-year limb-event C-statistic from 0.649 to 0.764 — a clinically meaningful discrimination jump.
The finding matters because vascular surgery risk stratification has long relied on LDL cholesterol and cardiac indices that miss active atherosclerotic plaque biology. cFAS — a liver-derived enzyme whose serum levels correlate with arterial plaque FAS content independently of LDL — offers a window into disease activity that standard lipid panels simply cannot provide. The complementary split is particularly compelling: cFAS tracks limb-ischemic and mortality risk while mFI-5 captures cardiac vulnerability, suggesting they probe genuinely different pathophysiological axes.
Limitations are substantial. This is a single-center, retrospective observational cohort, so unmeasured confounding cannot be excluded. The cFAS assay is not yet standardized across laboratories, and the non-detectable/tertile classification introduces analytical subjectivity. Causal directionality remains unestablished. Importantly, this is a preprint posted to medRxiv and has not yet undergone peer review — findings, statistical models, and conclusions may change materially. If validated prospectively, cFAS could represent a genuinely paradigm-shifting addition to preoperative vascular risk assessment.