Bridging the Diagnostic Gap in Peripheral Arterial Disease (PAD): Leveraging Fatty Acid Binding Protein 3 (FABP3) for Biomarker-Guided Detection

Background/Objective: Peripheral arterial disease (PAD) is a widespread but underdiagnosed manifestation of systemic atherosclerosis, associated with high morbidity and mortality. Traditional diagnostic methods such as the ankle-brachial index (ABI) have limited sensitivity in certain populations, highlighting the need for reliable blood-based biomarkers. Fatty Acid Binding Protein 3 (FABP3) has emerged as a robust biomarker with diagnostic utility in PAD. To evaluate the diagnostic performance of FABP3 when used in combination with traditional clinical risk factors for PAD in patients presenting to vascular surgery clinics. Methods: A retrospective analysis was conducted on 657 patients presenting to ambulatory vascular surgery clinics at St. Michael’s Hospital. Two logistic regression models were compared: (1) Model A: Included standard clinical risk factors (calf pain, age, smoking, diabetes, hypertension, hypercholesterolemia, coronary artery disease, and signs of chronic limb-threatening ischemia); and (2) Model B: Included the same factors as Model A, plus FABP3 levels. Diagnostic metrics including area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were assessed. Results: Among 657 patients, 423 had PAD and 234 did not. Model B (FABP3-integrated model) outperformed Model A, with a higher AUC (0.86 vs. 0.82), sensitivity (96% vs. 81%), specificity (84% vs. 67%), PPV (92% vs. 81%), NPV (94% vs. 65%), and diagnostic accuracy (93% vs. 76%). FABP3 also improved detection in asymptomatic PAD patients (84% detected vs. 0%). Conclusions: Integrating FABP3 with standard clinical risk factors significantly improves PAD diagnosis, especially in asymptomatic and borderline cases. These findings support the potential role of FABP3 in routine PAD screening, warranting further prospective studies for validation.