{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T05:04:44Z","timestamp":1779512684590,"version":"3.53.1"},"reference-count":76,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032613","name":"Blair Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032613","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Peripheral artery disease (PAD) impacts more than 200 million individuals globally. Despite its prevalence, management remains suboptimal, partly due to the lack of reliable blood-based biomarkers. The ankle\u2013brachial index (ABI), the current gold-standard test for PAD, is limited by inter-operator variability, misinterpretation, and reduced accuracy in patients with diabetes. Fatty acid binding protein 3 (FABP3) has emerged as a potential biomarker for PAD; however, its prognostic performance relative to ABI remains unclear. This study compared FABP3 and ABI for predicting PAD outcomes using statistical and machine learning approaches. Methods: A total of 1001 participants were prospectively recruited, including 644 patients with PAD and 357 without PAD. The primary outcome was 2-year major adverse limb event (MALE), defined as a composite of vascular intervention, major amputation, or acute limb ischemia. At enrollment, plasma FABP3 was quantified using a validated multiplex immunoassay. Kaplan\u2013Meier analysis of MALE-free survival was performed across pre-specified FABP3 tertiles (high [&gt;3.55 ng\/mL], moderate [1.55\u20133.55 ng\/mL], and low [&lt;1.55 ng\/mL]) and ABI tertiles (severe [&lt;0.40], moderate [0.40\u2013&lt;0.70], and mild [0.70\u20130.90]), with curve separation assessed using log-rank tests. Multivariable Cox proportional hazards modelling was used to evaluate the independent relationships of FABP3 and ABI with 2-year MALE after adjustment for baseline demographic and clinical covariates. To assess predictive performance for 2-year MALE, an extreme gradient boosting (XGBoost) classification model incorporating 10-fold cross-validation was trained using a combination of clinical covariates, plasma FABP3 levels, and ABI. Discriminatory performance was assessed using the area under the receiver operating characteristic curve (AUC). Results: The average participant age was 68 years (SD 12), and 34% (n = 340) were women. Mean ABI was 0.75 \u00b1 0.25 and mean FABP3 concentration was 2.97 \u00b1 2.06 ng\/mL. Among the 644 participants with PAD, 558 (86.6%) had complete time-to-event data for MALE status, FABP3, and ABI. Over the median follow-up period of 2 years, 140 (25.1%) participants with PAD experienced MALE. Kaplan\u2013Meier analyses demonstrated significant separation in MALE-free survival across FABP3 tertiles (log-rank p &lt; 0.001). At 24 months, MALE-free survival was 100.0% in the FABP3 &lt; 1.55 group, compared with 71.1% in the FABP3 1.55\u20133.55 group and 67.7% in the FABP3 &gt; 3.55 group. In contrast, ABI severity groups showed less pronounced separation, with 24-month MALE-free survival rates of 80.3% for mild ABI, 73.2% for moderate ABI, and 71.3% for severe ABI, without a statistically significant overall difference (p = 0.170). In adjusted Cox proportional hazards models, FABP3 demonstrated strong prognostic performance for 2-year MALE. A 1 SD increase in log-transformed FABP3 was independently associated with a higher risk of 2-year MALE (HR 1.90, 95% CI 1.60\u20132.25; p &lt; 0.001), with minimal change after additional adjustment for ABI (HR 1.90, 95% CI 1.60\u20132.24; p &lt; 0.001). Machine learning analyses similarly favored FABP3 over ABI, with the FABP3-based model achieving an AUC of 0.773 compared to 0.686 for the ABI-based model. Adding ABI to the FABP3 model did not improve discrimination. Conclusions: Circulating plasma levels of FABP3 are strongly associated with PAD outcomes. Specifically, FABP3 demonstrated a stronger and more robust association with 2-year MALE compared to ABI. This study validates the prognostic value of FABP3 for PAD outcomes in comparison to ABI.<\/jats:p>","DOI":"10.3390\/biom16050735","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T10:07:47Z","timestamp":1779444467000},"page":"735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of Fatty Acid Binding Protein 3 and Ankle Brachial Index for Predicting Peripheral Artery Disease Outcomes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7191-1034","authenticated-orcid":false,"given":"Ben","family":"Li","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Division of Vascular Surgery, St. Michael\u2019s Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, ON M5B 1W8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Temerty Centre for Artificial Intelligence Research and Education in Medicine (T-CAIREM), University of Toronto, Toronto, ON M5S 1A1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaima","family":"AlQrain","sequence":"additional","affiliation":[{"name":"Heart, Vascular, & Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi 112412, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, St. Michael\u2019s Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"G\u00f6b\u00f6l\u00f6s","sequence":"additional","affiliation":[{"name":"Heart, Vascular, & Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi 112412, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman","family":"Zamzam","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, St. Michael\u2019s Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawand","family":"Abdin","sequence":"additional","affiliation":[{"name":"Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Qadura","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Division of Vascular Surgery, St. Michael\u2019s Hospital, Unity Health Toronto, University of Toronto, 30 Bond Street, Suite 7-076, Toronto, ON M5B 1W8, Canada"},{"name":"Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A1, Canada"},{"name":"Heart, Vascular, & Thoracic Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi 112412, United Arab Emirates"},{"name":"Li Ka Shing Knowledge Institute, St. Michael\u2019s Hospital, Unity Health Toronto, University of Toronto, Toronto, ON M5B 1W8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","unstructured":"Zemaitis, M.R., Boll, J.M., and Dreyer, M.A. (2021). 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