Glycative and oxidative stress are associated with altered thrombus composition in diabetic patients with ST-elevation myocardial infarction

The role of type 2 diabetes (T2DM) on composition of thrombus has not been fully characterized in patients with ST-elevation myocardial infarction (STEMI). To elucidate the differences between diabetic and non-diabetic patients with STEMI in relation to the composition of coronary thrombus, and the potential association of these differences with glycated haemoglobin levels and markers of oxidative stress. Intracoronary thrombi from consecutive thrombus aspiration procedures in STEMI patients, 25 diabetic and 28 non-diabetic, were analyzed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, vWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34+) were measured in peripheral blood, and the oxidative capacity of plasma as indirect measure of oxidative stress was measured in parallel. Patients with T2DM had higher levels of fibrin (P=0.03), P-selectin (P=0.0001), PAI-1 (P=0.03) and vWF (P=0.006) in the thrombus and higher plasma TF activity (P=0.01) compared to non-diabetics. TF activity and plasmin correlated with HbA1C levels (R2=0.71, P=0.0001; R2=0.46, P=0.04, respectively) and TF was inversely correlated with TFPI (R2=−0.44, P=0.008) and tPA (R2=−0.48, P=0.003). Diabetic patients showed a higher oxidative response of plasma (26.47±6.88% vs 22.06±6.96% of oxidized lipids, P=0.04) (measured by H-NMR spectroscopy) that was associated to increased fibrin content into thrombus (R2=0.76, P=0.01). Diabetic patients with STEMI display an increased thrombogenicity that results in a different thrombus composition respect to non-diabetic patients with STEMI. The increased thrombogenicity present in T2DM is related to higher glycoxidative stress, as quantified by HbA1C levels and oxidative response in plasma.