Abstract 16877: High Serum Levels of Trefoil Factor 3 are Associated With an Increased Risk for Cardiovascular Events

Abstract

Introduction: Trefoil factor 3 (TFF3), first described in the intestine has general growth but also angiogenic properties. Recently a role in cancer and inflammation was found. Classic cardiovascular risk factors have less predictive power for morbidity and mortality in patients with peripheral arterial disease (PAD) compared to patients with coronary heart disease (CHD). Hypothesis: Serum TFF3 levels are able to predict major adverse cardiovascular events (MACE) in patients with PAD. Methods: We applied bead array technology to assess the serum levels of TFF3 in 359 patients of a prospective, on-going, long-term follow-up PAD study. First MACE was used as outcome parameter, defined as occurrence of any death, non-fatal myocardial infarction or non-fatal stroke. Statistical analysis were performed including univariate correlations, Receiver Operating Characteristic (ROC) curves, students t-test , ANOVA, Kaplan-Meier (KM)-analysis and Cox-regression. Results: Patients with systemic atherosclerosis defined as concomitant PAD, CHD and cerebrovascular disease had significant higher levels of TFF3 (59.38±20.86 ng/ml) at baseline compared to patients with only one (47.22±18.10 ng/ml; p=0.001) or two (49.12±19.43 ng/ml; p=0.006) manifestations of atherosclerosis. KM-analysis demonstrated a significant lower event-free survival for the fourth quartile of TFF3 (71.1%) compared to the other (88.1%) (Log-rank: p<0.001). By using ROC a cut-off for TFF3 of 56.18 ng/ml was defined (sensitivity 56.9%; specifity 72.1%). A multivariable Cox regression model adjusted for age, gender, LDL-Cholesterol, systolic blood pressure, eGFR, diabetes status, smoking status and CRP showed that patients with TFF3 levels higher than 56.18 ng/ml had a hazard ratio of 2.77 (95%Cl: 1.38 - 5.58) for experiencing MACE. Conclusions: Our data imply a significant association of serum Trefoil Factor 3 and the occurrence of MACE in patients with atherosclerosis. This association of Trefoil Factor 3 and MACE was unchanged by C-reactive protein. Whether the association of Trefoil Factor 3 is causal, or a consequence of advanced atherosclerosis should be investigated in future trials containing time courses of Trefoil Factor 3 and MACE.