Circulating Fatty Acid Synthase and Modified Frailty Index-5 Are Additive Predictors of Adverse Outcomes After Elective Vascular Surgery
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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?
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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.
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cFAS and the 5-item modified frailty index (mFI-5) captured complementary and additive dimensions of postoperative risk: disease activity and physiologic reserve, respectively.
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Combining cFAS with the mFI-5 improved risk discrimination beyond standard clinical covariates for all endpoints examined.
What Are the Clinical Implications?
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cFAS may identify residual atherosclerotic risk not captured by standard lipid panels, offering a novel dimension of preoperative assessment in vascular surgery.
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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.
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Prospective external validation is warranted before cFAS is adopted as an adjunct to established preoperative cardiovascular risk assessment in vascular surgery.
