P5537Biomarkers in addition to clinical characteristics for prediction of peripheral artery disease in patients with recent myocardial infarction
Authors: Jonelid B , Christersson C , Hedberg P , Leppert J , Lindhagen L , Oldgren J , Lindahl B , Siegbahn A 
Published: October 2019

Abstract

Background
Peripheral artery disease (PAD) is associated with increased risk of cardiovascular events and mortality. PAD is underdiagnosed in patients admitted for myocardial infarction (MI).

Purpose
To evaluate whether biomarkers in addition to clinical characteristics could improve the identification of PAD in MI patients.

Methods
Two prospectively observational studies including unselected patients with recent ST-elevation or non-ST elevation MI were used for the analyses. PAD was defined as abnormal ankle brachial indexes (ABI) score (<0.9 or >1.4) on at least one side. The Proximity Extension Assay (PEA) technique was used to simultaneously analyze 92 biomarkers with association to cardiovascular disease (CVD I and III, Olink Proteomics) in samples early after the acute MI. Random forest was used to identify the biomarkers with higher association to PAD. The discriminating accuracy of adding biomarkers to clinical characteristics including age, sex, diabetes mellitus, hypertension and smoking were analyzed by the c-statistic.

Results
In the REBUS cohort (n=420) the mean age was 67 years, 22.1% were women, 26.4% were smoking, 16.2% had diabetes and 53.3% hypertension. In the VAMIS cohort (n=998) the mean age was 71 years, 33.5% were women, 19.9% were smoking, 18.1% and 49.9% had diabetes and hypertension, respectively. PAD was found in 20.0% and 22.8% of the patients in the REBUS and VAMIS cohort, respectively. Six biomarkers associated with PAD (Tnfrsf 14, tnf r2, tnf r1, GDF-15, IL-6 ra, ctsd) were identified in the REBUS cohort and validated in the VAMIS cohort.
Additional predictive value of the biomarkers compared to the performance of the model with clinical characteristics, as measured by the c-statistic Clinical characteristics (CC) CC + Tnfrsf14 CC + Tnf r2 CC + Tnf r1 CC + GDF-15 CC + IL-6 ra CC + ctsd REBUS (n=420) 0.683 (0.610,0.756) 0.702 (0.632, 0.772) 0.703 (0.633, 0.773) 0.709 (0.640, 0.779) 0.710 (0.640, 0.781) 0.682 (0.608, 0.775) 0.683 (0.610, 0.757) VaMIS (n=998) 0.729 (0.687, 0.770) 0.732 (0.691, 0.733) 0.745 (0.704, 0.785) 0.746 (0.706, 0.787) 0.752 (0.711, 0.792) 0.729 (0.688, 0.770) 0.736 (0.695, 0.777) Tnfrsf 14 = tumor necrosis factor receptor superfamily member 14; Tnf r2 = tumor necrosis factor receptor 2; Tnf r1 = tumor necrosis factor receptor 1; GDF-15 = growth differentiation factor 15; IL-6 ra = interleukin-6 receptor subunit alpha; ctsd = Cathepsin D.

Conclusion
Out of a large panel of biomarkers, tumor necrosis factor and its receptors and GDF-15 were identified associated with PAD in MI patients.
In this underdiagnosed manifestation of atherosclerosis in MI patients, clinical characteristics are strong predictors of PAD, but the cytokines may have an additional value. Further studies focusing on more widespread atherosclerosis in acute coronary syndrome might identify a patient group with benefit of treatment targeting inflammation.

Acknowledgement/Funding
None