Circulating Fatty Acid Synthase and Modified Frailty Index-5 Are Additive Predictors of Adverse Outcomes After Elective Vascular Surgery

Background Preoperative risk assessment in vascular surgery relies on clinical scores and lipids that do not capture atherosclerotic disease activity. Circulating fatty acid synthase (cFAS) is a liver-derived enzyme whose concentration correlates with arterial plaque FAS content independent of LDL. The 5-item modified frailty index (mFI-5) is a validated predictor of postoperative mortality. Whether cFAS predicts outcomes after vascular surgery, and whether combining it with the mFI-5 improves risk discrimination, have not been examined. Methods We studied 657 patients undergoing elective vascular surgery at a single center (2014 to 2023). cFAS was classified as non-detectable (n = 306) or, among detectable values, by tertiles (n = 117 each). Multivariable Cox models assessed associations with major adverse events (MAE), major adverse cardiovascular events (MACE), major adverse limb events (MALE), reintervention, and mortality, and Harrell’s C-statistic quantified the incremental discrimination gained by adding cFAS and the mFI-5 to standard clinical covariates. Results High serum cFAS was independently associated with 5-year MAE (adjusted hazard ratio [aHR] 1.94; 95% CI 1.31-2.85), mortality (aHR 1.77; 1.05 to 3.00), MALE (aHR 4.53; 2.04 to 10.05), and reintervention (aHR 2.50; 1.37 to 4.57), but not MACE. Severe frailty (mFI-5 of 3 or higher) was associated with MACE (aHR 2.69; 1.29 to 5.58) and MAE (aHR 2.46; 1.30 to 4.65) but not limb endpoints at 1 year. Adding cFAS raised the 1-year MALE C-statistic from 0.649 to 0.764; the combined model yielded the highest discrimination. Conclusions cFAS and mFI-5 were independently and additively associated with adverse outcomes after elective vascular surgery. cFAS was associated with limb events and mortality, the mFI-5 with cardiovascular events. Combining them improved discrimination over standard covariates. CLINICAL PERSPECTIVE What Is New? A single preoperative measurement of circulating fatty acid synthase (cFAS) independently predicted adverse outcomes after elective vascular surgery, establishing cFAS as a prognostic biomarker of atherosclerotic disease activity beyond its previously reported diagnostic role. cFAS and the 5-item modified frailty index (mFI-5) captured complementary and additive dimensions of postoperative risk: disease activity and physiologic reserve, respectively. Combining cFAS with the mFI-5 improved risk discrimination beyond standard clinical covariates for all endpoints examined. What Are the Clinical Implications? cFAS may identify residual atherosclerotic risk not captured by standard lipid panels, offering a novel dimension of preoperative assessment in vascular surgery. Incorporating a routine frailty assessment (mFI-5) alongside a disease-activity biomarker (cFAS) could enhance preoperative risk stratification by addressing two distinct and additive determinants of surgical outcome. Prospective external validation is warranted before cFAS is adopted as an adjunct to established preoperative cardiovascular risk assessment in vascular surgery.