Impact of inflammatory state and metabolic control on responsiveness to dual antiplatelet therapy in type 2 diabetics after PCI: prognostic relevance of residual platelet aggregability in diabetics undergoing coronary interventions.

BACKGROUND: Type-2 diabetes is accompanied by a prothrombotic state influenced by endothelial dysfunction, inflammatory condition and platelet hyperreagibility. We aimed to characterize the relationship of inflammation and residual platelet aggregability (RPA) under antiplatelet therapy with regard to prognosis in an unselected PCI-cohort of diabetics. METHODS: In a first step, a consecutive collective of 75 type 2 diabetics compared to 153 non-diabetic controls was evaluated at the time of PCI. Inflammatory markers, Interleukin 6 and C-reactive protein were measured by immunoassays. ADP and Aspirin assays were performed by multiple electrode aggregometry. Then, we consecutively evaluated ADP-induced RPA in 542 diabetics and 1,161 non-diabetics undergoing PCI and treated by standard antiplatelet therapy. Major CV-events were assessed at 30 days after PCI. RESULTS: Inflammatory markers were significantly increased in diabetics with peri-interventional hyperglycemic state and inversely correlated with responsiveness to clopidogrel and aspirin. In a large scale cohort, diabetics showed a higher RPA compared to non-diabetics (median 38.1 vs. 28.8%; p < 0.001). After adjustment for relevant co-factors, diabetes remained a strong predictor for increased RPA (OR 4.39; 95% CI 1.95-6.83; p < 0.001). Furthermore, diabetics with high RPA had an increased risk for 30-day MI and CV-death than diabetics with low RPA (adjusted HR 1.05; 95% CI 1.02-1.07; p < 0.001). CONCLUSIONS: We demonstrate that peri-interventional inflammatory degree and glycaemic control correlate with decreased antiplatelet drug responsiveness in diabetics. In addition, we identified high RPA as strong predictor for short-term CV-events in this group. Therefore, approaches to treat these entities are needed to improve outcome in diabetics undergoing PCI.

Expression of stromal-cell-derived factor-1 on circulating platelets is increased in patients with acute coronary syndrome and correlates with the number of CD34+ progenitor cells.

AIMS: Previous experimental studies have suggested that platelet stromal-cell-derived factor-1 (SDF-1) regulates mobilization and recruitment of haematopoietic progenitor cells supporting revascularization in mice. However, there are no clinical data available regarding platelet-bound SDF-1 in patients with acute coronary syndrome (ACS). The objective of this study was to evaluate the platelet-surface expression of SDF-1 in patients with ACS. METHODS AND RESULTS: Patients with ACS (n = 418) showed a significantly enhanced SDF-1 expression on admission compared with those with stable angina pectoris (SAP, n = 486) [SAP (mean fluorescence intensity (MFI) +/- SD): 13.48 +/- 5.27; ACS: 18.45 +/- 12.85; P < 0.001) independent of cardiovascular risk factors and medication. Enhanced platelet-bound SDF-1 expression was found in patients with reduced left ventricular ejection fraction (LVEF <55%) in comparison to patients with normal LVEF (P = 0.005). Platelet-bound SDF-1 expression positively correlated with the degree of platelet activation [CD62P: r = 0.325; glycoprotein VI (GPVI): r = 0.277; PAC-1: r = 0.501; P < 0.001 for all] and showed a significant, but slight association with plasma levels of SDF-1 (r = 0.084; P = 0.045). In a subgroup of patients with coronary artery disease, platelet-bound SDF-1, but not other platelet activation markers, significantly correlated with the number of circulating CD34(+) progenitor cells (r = 0.252; P = 0.002) or CD34(+)/CD133(+) endothelial progenitor cells (r = 0.352; P = 0.008). CONCLUSION: Platelet-bound SDF-1 may play an important role in peripheral homing of circulating progenitor cells thus in tissue regeneration.