Abstract
BACKGROUND: No reliable serum diagnostic test currently exists for peripheral arterial disease (PAD). We previously observed that serum circulating Fatty Acid Synthase (cFAS) is elevated in individuals with chronic limb threatening ischemia (CLTI). OBJECTIVES: We hypothesized that cFAS can be an independent diagnostic biomarker for PAD and CLTI. METHODS: Patients with/without PAD and CLTI were retrospectively reviewed. Total serum cFAS content was evaluated using ELISA and normalized to total protein. Patient demographics and PAD incidence were collected via chart review. Serum cFAS and demographics were compared, and regression analysis was used to determine the correlation between cFAS and PAD incidence, and the impact of co-morbidities on cFAS content. RESULTS: A total 347 patients met inclusion criteria. Of these, 34 were healthy controls without PAD (Group 1), 164 had PAD (Group 2), and 149 had CLTI (Group 3). Compared to Group 1, the remaining groups were significantly older, had more males, and had higher incidence of cardiovascular co-morbidities (p<0.001). Compared to Group 1, Groups 2 and 3 had significantly higher serum cFAS content (p=0.007). ROC analysis revealed an optimal cutoff of 340pg/mg protein for cFAS in distinguishing between individuals with or without PAD (p<0.001), and 490pg/mg protein in distinguishing between those with PAD and those with CLTI (p=0.015). CONCLUSIONS: Our study demonstrates that cFAS is an independent serum-based diagnostic biomarker for PAD, can distinguish between patients with PAD versus CLTI, and may serve as a predictive variable for identifying patients with highest risk of disease progression. CONDENSED ABSTRACT: There are currently no reliable serum biomarkers to aid in the diagnosis of peripheral arterial disease (PAD). We hypothesized that circulating Fatty Acid Synthase (cFAS) can be an independent diagnostic biomarker for PAD. Serum cFAS and demographics were compared for patients with and without PAD or CLTI. Patients with PAD or CLTI had significantly higher serum cFAS content. We observed optimal cutoffs for cFAS in distinguishing between individuals with and without PAD or CLTI. Our study demonstrates that cFAS is an independent serum-based diagnostic biomarker for PAD, can distinguish between patients with PAD versus CLTI, and may predict disease severity.