Changes in platelet function independent of pharmacotherapy following coronary intervention in non-ST-elevation myocardial infarction patients.

BACKGROUND: High on treatment platelet reactivity (HTPR) is common in patients receiving clopidogrel following an acute coronary syndrome (ACS); it's also associated with increased morbidity and mortality. More potent and predictable antiplatelet drugs have addressed this issue at the expense of increased bleeding. Identification of HTPR and the targeted use of more potent antiplatelet drugs has, so far, broadly failed. We investigate this approach in terms of the timing of platelet function testing and how this can impact on the ability of these bedside tests to predict HTPR around the time of coronary intervention. METHODS: High risk ACS patients treated with 5 days of clopidogrel had platelet function assessed using the multiple electrode aggregometry system (MEA) pre, post and 24 h following percutaneous coronary intervention (PCI). Simultaneous detailed analysis of platelet status was undertaken with quantification of platelet bound and soluble p-selectin and mass spectrometry quantification of the eicosanoid 12-HETE. RESULTS: As assessed by MEA 40.5% of patients had HTPR pre-PCI; mean aggregation units (AU) in response to ADP were 499.1 ± 46.3 pre-PCI, 407.6 ± 37.7 post-PCI and 269.1 ± 24.6 AU 24 h post-PCI (pre to post PCI p > 0.05, pre to 24 h post-PCI p = 0.0002). This highly significant drop in platelet reactivity was contrasted with on-going expression of platelet bound p-selectin, increased soluble p-selectin and rising 12-HETE concentrations. CONCLUSIONS: This study outlines significant changes in ex-vivo platelet aggregation that occur within 24 h of PCI in high risk NSTEMI patients using bedside PFT. Whilst there were no changes in antiplatelet therapy during the study period its clear that timing is crucial when assessing high on treatment residual platelet activity.

Outcomes following PCI in patients with previous CABG: a multi centre experience.

BACKGROUND: Limited data is available to guide operators as to the optimal revascularisation strategy in patients with previous CABG representing with angina. METHOD: Retrospective analysis of 161 patients with prior CABG undergoing PCI in two centres between September 2005 and April 2008. RESULTS: 161 patients (132 male, 68 ± 8 years) underwent PCI at 126 ± 65 months after index CABG. Clinical presentation of recurrent ischaemia was stable in 59.7% and as an acute coronary syndrome in 40.3% of patients. Mean follow-up after PCI was 13.5 ± 4.8 months. About 62.7% of patients underwent native vessel PCI, 32.9% had a graft only PCI, and 4.4% having a combination of both. Drug eluting stents were used in 84.9% of cases. There was one cardiac death and one case of redo CABG during follow-up. Mean CCS angina class decreased from 2.87 to 0.67 (P < 0.0001) in the follow-up group. About 13.6 % of all patients had a MACE at follow up. This was higher in the graft PCI group (21.6% vs. 8.9%, P = 0.048). About 12.4% of the total cohort underwent repeat PCI although 30% of these required PCI for a de-novo lesion. TVR rate was significantly higher in patients undergoing graft PCI than native vessel PCI (15% vs. 4.9%, P = 0.031). Graft PCI was an independent predictor (HR 3.73, 1.27-10.87 [95%CI], P = 0.016) of MACE in these patients. CONCLUSION: PCI significantly improved angina in these patients with low overall rates of TVR. However TVR rate was significantly higher in patients undergoing graft PCI than those undergoing native vessel PCI.

The potential role of resistin in atherogenesis.

Resistin, an adipocyte-derived cytokine linked to insulin resistance and obesity, has recently been shown to activate endothelial cells (ECs). Using microarrays, we found that along with numerous other pro-atherosclerotic genes, resistin expression levels are elevated in the aortas of C57BL/6J apoE-/- mice; these findings led us to further explore the relation between resistin and atherosclerosis. Using TaqMan PCR and immunohistochemistry, we found that ApoE-/- mice had significantly higher resistin mRNA and protein levels in their aortas, and elevated serum resistin levels, compared to C57BL/6J wild-type mice. Incubation of murine aortic ECs with recombinant resistin increased monocyte chemoattractant protein (MCP)-1 and soluble vascular cell adhesion molecule (sVCAM)-1 protein levels in the conditioned medium. Furthermore, human carotid endarterectomy samples stained positive for resistin protein, while internal mammary artery did not show strong staining. Patients diagnosed with premature coronary artery disease (PCAD) were found to have higher serum levels of resistin than normal controls. In summary, resistin protein is present in both murine and human atherosclerotic lesions, and mRNA levels progressively increase in the aortas of mice developing atherosclerosis. Resistin induces increases in MCP-1 and sVCAM-1 expression in murine vascular endothelial cells, suggesting a possible mechanism by which resistin might contribute to atherogenesis. Finally, PCAD patients exhibited increased serum levels of resistin when compared to controls. These findings suggest a possible role of resistin in cardiovascular disease.