Abstract 133: Prognostic Utility of the GDF-15/FSTL-1 Axis for Adverse Cardiac and Limb Events in Patients With Peripheral Artery Disease

Abstract

Background: Peripheral artery disease (PAD) confers greater vulnerability to cardiovascular events. Inflammatory activation and tissue ischemia induce expression of a vasoprotective cytokine network including GDF15 and FSTL1. We sought to evaluate the clinical utility of novel vascular stress biomarkers for risk stratification in PAD. Methods and Results: We followed 245 PAD patients prospectively over two years for adverse cardiac events (n=40, myocardial infarction, unstable angina, coronary revascularization, transient ischemic event, stroke, congestive heart failure, cardiac death) and adverse limb events (n=52, worsening claudication, peripheral revascularization, critical limb ischemia, amputation, graft or stent failure). At baseline, we measured serum GDF15 and FSTL-1 and disease severity by the ankle-brachial index (ABI). In survival analyses, higher GDF15 was associated with both adverse cardiac and limb events (P<0.0001, P<0.01). FSTL-1 was associated with adverse limb (P=0.03) but not cardiac events. In multivariable models adjusting for relevant covariates including ABI, higher GDF15 remained associated with higher risk of limb events (HR 1.83, 95% CI 1.10, 3.06, P=0.02) and cardiac events (HR 1.92, 95% CI 1.09, 3.32, P=0.02). There was a trend for an association of higher FSTL1 with limb events (HR 2.34, 95% CI 0.93, 5.75, P=0.07). Addition of GDF15 to clinical variables led to an increase in the c statistic (P<0.05) and net reclassification improvement (P<0.01) for both cardiac and limb events. Conclusions: Our findings show that vascular stress markers involving the GDF15-FSTL1 axis provide additional prognostic value over clinical factors and disease severity for predicting adverse cardiac and limb events in patients with PAD.