{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:40:10Z","timestamp":1786714810236,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,12]]},"group-title":"Cardiovascular Medicine","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2019s C-statistic quantified the incremental discrimination gained by adding cFAS and the mFI-5 to standard clinical covariates.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CLINICAL PERSPECTIVE<\/jats:title>\n                  <jats:sec>\n                    <jats:title>What Is New?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>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.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>cFAS and the 5-item modified frailty index (mFI-5) captured complementary and additive dimensions of postoperative risk: disease activity and physiologic reserve, respectively.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Combining cFAS with the mFI-5 improved risk discrimination beyond standard clinical covariates for all endpoints examined.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>What Are the Clinical Implications?<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>cFAS may identify residual atherosclerotic risk not captured by standard lipid panels, offering a novel dimension of preoperative assessment in vascular surgery.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>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.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Prospective external validation is warranted before cFAS is adopted as an adjunct to established preoperative cardiovascular risk assessment in vascular surgery.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.10.26360144","type":"posted-content","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T22:10:11Z","timestamp":1786572611000},"source":"Crossref","is-referenced-by-count":0,"title":["Circulating Fatty Acid Synthase and Modified Frailty Index-5 Are Additive Predictors of Adverse Outcomes After Elective Vascular Surgery"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4682-0932","authenticated-orcid":false,"given":"Mohamed","family":"Zaghloul","sequence":"first","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Catlett","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bera","family":"Koklu","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Elahi","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Soltan","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jad","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wahid","family":"Abu-Amer","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gao","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6443-4527","authenticated-orcid":false,"given":"Mohamed A","family":"Zayed","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine, Department of Surgery, Section of Vascular Surgery, St. Louis, MO, USA"},{"name":"Washington University School of Medicine, Department of Radiology, St. Louis, MO"},{"name":"Washington University School of Medicine, Division of Molecular Cell Biology, St. Louis, MO"},{"name":"Washington University School of Medicine, Division of Surgical Sciences, St. Louis, MO"},{"name":"Washington University, McKelvey School of Engineering, Department of Biomedical Engineering, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081406200483000_2026.08.10.26360144v1.1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001303"},{"key":"2026081406200483000_2026.08.10.26360144v1.2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001258"},{"key":"2026081406200483000_2026.08.10.26360144v1.3","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000678"},{"key":"2026081406200483000_2026.08.10.26360144v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00215-5"},{"key":"2026081406200483000_2026.08.10.26360144v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"2026081406200483000_2026.08.10.26360144v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2019.05.016"},{"key":"2026081406200483000_2026.08.10.26360144v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature20117"},{"key":"2026081406200483000_2026.08.10.26360144v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-98479-7"},{"key":"2026081406200483000_2026.08.10.26360144v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-025-07656-1"},{"key":"2026081406200483000_2026.08.10.26360144v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2025.101411"},{"key":"2026081406200483000_2026.08.10.26360144v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2017.11.005"},{"key":"2026081406200483000_2026.08.10.26360144v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s11605-023-05743-4"},{"key":"2026081406200483000_2026.08.10.26360144v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2025.124709"},{"key":"2026081406200483000_2026.08.10.26360144v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2025.02.033"},{"key":"2026081406200483000_2026.08.10.26360144v1.15","doi-asserted-by":"publisher","DOI":"10.7326\/M19-250"},{"key":"2026081406200483000_2026.08.10.26360144v1.16","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14113737"},{"key":"2026081406200483000_2026.08.10.26360144v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(87)90171-8"},{"key":"2026081406200483000_2026.08.10.26360144v1.18","doi-asserted-by":"publisher","DOI":"10.1002\/ohn.70125"},{"key":"2026081406200483000_2026.08.10.26360144v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2023.01.007"},{"key":"2026081406200483000_2026.08.10.26360144v1.20","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303849"},{"key":"2026081406200483000_2026.08.10.26360144v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2021.01.068"},{"key":"2026081406200483000_2026.08.10.26360144v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2016.09.032"},{"key":"2026081406200483000_2026.08.10.26360144v1.23","doi-asserted-by":"publisher","DOI":"10.3390\/cells13080658"},{"key":"2026081406200483000_2026.08.10.26360144v1.24","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)61717-7"},{"key":"2026081406200483000_2026.08.10.26360144v1.25","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.4360"},{"key":"2026081406200483000_2026.08.10.26360144v1.26","doi-asserted-by":"publisher","DOI":"10.23736\/S0392-9590.23.05071-X"},{"key":"2026081406200483000_2026.08.10.26360144v1.27","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000005426"},{"key":"2026081406200483000_2026.08.10.26360144v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-025-00553-5"},{"key":"2026081406200483000_2026.08.10.26360144v1.29","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107477"},{"key":"2026081406200483000_2026.08.10.26360144v1.30","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055373"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.08.10.26360144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:20:11Z","timestamp":1786713611000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.08.10.26360144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":30,"URL":"https:\/\/doi.org\/10.64898\/2026.08.10.26360144","relation":{},"subject":[],"published":{"date-parts":[[2026,8,12]]},"subtype":"preprint"}}