Serum Trefoil Factor-3 Predicts Survival in Peripheral Artery Disease

Trefoil factor 3 (TFF3) has been studied in processes leading to atherosclerosis. Data are scarce in manifest disease and missing in peripheral artery disease (PAD). This study aims to elucidate TFF3 with disease stages, degrees of atherosclerosis, and outcomes. TFF3 was measured in serum in 364 PAD patients without critical limb ischemia and mild to moderate chronic kidney disease (CKD). Mortality data were retrieved from the Austrian central death registry (median observation 9.6 years). Survival analyses were performed using Cox regression and the Kaplan-Meier method. A negative association between ankle-brachial index and TFF3 (P < .001) was observed, while levels were similar in asymptomatic and symptomatic PAD. TFF3 increased with history of cardiovascular and cerebrovascular disease (P < .001). TTF3 was associated with the estimated glomerular filtration rate (R = -0.617, P < .001) and urinary albumin-creatinine ratio (R = 0.229, P < .001). One SD increase in TFF3 showed a worsening in all-cause mortality (hazard ratio 1.68, CI 1.37-2.05) which persisted after multiple adjustment for cardiovascular risk, inflammatory, and angiogenetic markers (hazard ratio 1.35, CI 1.01-1.81). This study is the first to link TFF3 with both disease markers and outcomes in PAD. TFF3 demonstrated associations with renal function, PAD severity measured by ankle-brachial index, and additional atherosclerotic burden in PAD.