Low responsiveness to clopidogrel increases risk among CKD patients undergoing coronary intervention.

Patients with CKD are at higher risk for major events after percutaneous coronary intervention (PCI) compared with subjects with normal renal function. The aims of this study were to evaluate responsiveness to clopidogrel in patients with CKD and to examine the effect of antiplatelet drug response on post-PCI outcome. We retrospectively evaluated a consecutive cohort of 1567 patients with symptomatic coronary artery disease undergoing PCI, 648 (41%) of whom had stage 3 to 5 CKD.

Plaque distribution in clopidogrel responders and low responders as determined by multislice computed tomography.

Via multidetector computed tomography (MDCT) with retrospective electrographic gating, we sought to evaluate whether plaque distribution differs between responders and low responders to clopidogrel treatment. Low response was defined as a post-treatment aggregation of 35% to 70%. In this observational study, we enrolled 62 patients (mean age, 64.

Impact of inflammatory markers on platelet inhibition and cardiovascular outcome including stent thrombosis in patients with symptomatic coronary artery disease.

Background: There is cumulative evidence that the degree of inflammation correlates with prognosis after percutaneous coronary interventions (PCI). Additionally, there is a cross-link between platelet activation and inflammatory pathways. The aim of the present analysis was to evaluate the association of inflammatory markers and effects of dual antiplatelet therapy on platelet function and outcome in patients undergoing PCI.

Single-molecule force spectroscopy of supramolecular heterodimeric capsules.

The specific interaction of a supramolecular binding motif was quantitatively evaluated by dynamic single-molecule force spectroscopy (SMFS) using an atomic force microscope (AFM). The supramolecular capsule forms by two different cavitands stitched together by four hydrogen bonds between carboxylic acid and pyridyl groups. The tetra(carboxyl)cavitand is monofunctionalized at the lower rim with a flexible poly(ethylene glycol) linker and attached to the AFM sensor tip.

Distributed characterization of bending effects on the birefringence of single-mode optical fibers.

The effects of bending on randomly birefringent, single-mode optical fibers have been analyzed by means of polarization-sensitive optical frequency domain reflectometry. This distributed, pointwise characterization has been performed on ad hoc drawn spun fibers and on a ribbon cable. Experimental results are in agreement with the theoretical predictions and confirm the effectiveness of reflectometry as a means to characterize polarization properties of optical fibers.

Management of perioperative stent thrombosis in patients undergoing surgery.

Surgery often requires the interruption of standard dual antiplatelet therapy using aspirin and clopidogrel. Here, we present three patients who underwent surgery and suffered from a perioperative stent thrombosis associated with premature discontinuation of dual antiplatelet therapy. Although there are missing evidence-based data and key guidelines, we suggest that patients who undergo surgery after coronary stenting may benefit from an individualized perioperative antiplatelet management strategy.

Current strategies in antiplatelet therapy--does identification of risk and adjustment of therapy contribute to more effective, personalized medicine in cardiovascular disease?

There is a wide consensus that intensified antiplatelet therapy contributes to the reduction of major atherothrombotic complications in cardiovascular (CV) disease. In the setting of PCI (percutaneous coronary intervention) and acute coronary syndromes, dual antiplatelet therapy at optimal dosing and timing has significantly lowered the risk of thrombotic complications. There is a growing body of evidence that there is variability in response to antiplatelet treatments and this represents a potentially important clinical problem.

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.

What goes into a major acute coronary syndrome trial and what will future trials look like?

Acute coronary syndromes (ACS) are common and carry a high risk of death and serious complications. Over the past three decades, the international cardiology community has collaborated in numerous large, well-designed randomized trials evaluating promising new treatments leading to important improvements in care for patients with ACS. Industry has funded most of the ACS trials of new pharmacologic treatments, but there are many independently funded trials evaluating treatment strategies such as percutaneous coronary intervention.

Platelet aggregates-induced human CD34+ progenitor cell proliferation and differentiation to macrophages and foam cells is mediated by stromal cell derived factor 1 in vitro.

The chemokine stromal cell derived factor 1 (SDF-1) regulates chemotactic recruitment (homing) and differentiation of CD34 (+) stem cells. Platelets express substantial amounts of SDF-1 upon activation. The aim of the present study was to evaluate the role of SDF-1 in platelet-induced proliferation and differentiation of human CD34 (+) cells to macrophages and foam cells, as well as in regulation of matrix metalloproteinase (MMP)-9 secretion.

Junctional adhesion molecule A expressed on human CD34+ cells promotes adhesion on vascular wall and differentiation into endothelial progenitor cells.

Objective: To investigate the role of junctional adhesion molecule A (JAM-A) on adhesion and differentiation of human CD34(+) cells into endothelial progenitor cells.

Methods And Results: Tissue healing and vascular regeneration is a multistep process requiring firm adhesion of circulating progenitor cells to the vascular wall and their further differentiation into endothelial cells. The role of JAM-A in platelet-mediated adhesion of progenitor cells was investigated by adhesion assays in vitro and with the help of intravital fluorescence microscopy in mice.

Platelet pharmacogenomics.

Platelet responsiveness to conventional antiplatelet therapy underlies a high interindividual variability influenced by various factors. For instance, antiplatelet therapy does not curtail the expected effects in a relevant number of patients as demonstrated by the occurrence of repeated cardiovascular events including stent thrombosis and/or by inadequate platelet inhibition measured by in vitro platelet function assays. Besides non-genetic factors such as age, gender, liver and renal function and co-medication, considerable variation of antiplatelet drug responsiveness can be attributed to genetic factors including polymorphisms and genetic variants of platelet surface proteins and drug metabolizing enzymes.

Platelet glycoprotein VI (GPVI) for early identification of acute coronary syndrome in patients with chest pain.

Background: Platelet glycoprotein VI (GPVI) is elevated in patients with acute coronary syndrome (ACS), stroke and associated with acute coronary events. GPVI may be helpful to distinguish an imminent ACS from non-coronary (NC) causes in patients with chest pain who were transferred to chest pain unit, before the myocardial necrosis is evident with classical biomarkers.

Methods: Based on the findings of our previous studies, we consecutively examined 1004 patients with chest pain in a prospective study design.

Increased circulating progenitor cells in Alzheimer's disease patients with moderate to severe dementia: evidence for vascular repair and tissue regeneration?

Cerebrovascular dysfunction is a common finding in patients with Alzheimer's disease (AD) and may contribute to cognitive decline. Abundant evidence suggests that vascular and neuronal repair mechanisms are mediated by circulating progenitor cells in vivo. Whether CD34+ and, specifically, CD34+/CD133+ progenitor cells are involved in the pathophysiology of AD is poorly understood so far.

ADP-receptor blockade: A case for personalised pharmacotherapy?

The dual antiplatelet therapy consisting of aspirin and the ADP-receptor blocker clopidogrel is the current standard medication after acute coronary events. However, clopidogrel is characterised by a high interindividual response variability, insufficient inhibition of platelet aggregation in a significant number of patients, relatively slow onset of efficacy and potential interaction with different co-medication via diverse hepatic cytochrome enzymes. In various trials, response variability of clopidogrel was translated into a higher rate of recurrent cardiovascular events.

Glycoprotein VI for diagnosis of acute coronary syndrome when ECG is ambiguous.

Background: The purpose of the study was to test whether an elevated surface expression of platelet collagen receptor glycoprotein VI (GPVI) is an appropriate marker for the diagnosis of the acute coronary syndrome (ACS), especially when the electrocardiogram (ECG) is ambiguous.

Methods: Between 2007 to 2008, we consecutively evaluated 378 patients with ACS and ambiguous ECG on hospital admission. In all patients, GPVI surface expression was determined by flow cytometry.

Glycoprotein VI as a prognostic biomarker for cardiovascular death in patients with symptomatic coronary artery disease.

Background: Platelets play a critical role in arterial thrombosis, acute coronary syndrome (ACS) and stroke. Platelet collagen receptor glycoprotein VI (GPVI) is associated with acute coronary events and a poor clinical outcome.

Methods: Between January 2006 and March 2009, we evaluated 2,213 consecutive patients in a prospective study design, who presented with chest pain.

Catheter-based delivery of fluid paclitaxel for prevention of restenosis in native coronary artery lesions after stent implantation.

Background: Stents eluting antiproliferative drugs reduce the incidence of restenosis but delay healing of the vascular wall. We assessed the safety and efficacy of catheter-based local delivery of fluid paclitaxel in patients with coronary de novo stenoses after implantation of a bare metal stent.

Methods And Results: We conducted a prospective, randomized trial comparing the local delivery of fluid paclitaxel after bare metal stent implantation (group I) with the implantation of a bare metal stent (group II) and the implantation of a paclitaxel-eluting stent (group III) in 204 patients.

High plasma levels of adipocytokines are associated with platelet activation in patients with coronary artery disease.

Previous studies suggested that the adipocytokines, adiponectin and leptin, are associated with the progression and prognosis of coronary artery disease (CAD). The aim of this study was to differentially evaluate plasma levels of adiponectin and leptin in patients with CAD and their association with conventional laboratory parameters and markers of platelet activation. We consecutively evaluated 220 patients, who presented with a symptomatic CAD.

Individualized antiplatelet therapy: what can a clinical score contribute?

Safeguarding of antiplatelet drug efficacy represents a cornerstone for the optimal treatment of patients with symptomatic coronary artery disease requiring coronary interventions. This means a challenge to modern cardiology since there has been cumulative evidence, that response to common oral antiplatelet therapy is a highly variable phenomenon underlying various mechanisms. It is known, that particular risk groups exhibit a high residual platelet aggregability (RPA) despite conventional antiplatelet therapy.

Persistent troponin elevation in a patient with cardiac amyloidosis.

A 79-year-old patient repeatedly presented with chest discomfort and dyspnea on exertion. With echocardiography a prominent left ventricular and septal hypertrophy was detected with reduced left ventricular function. Despite successful revascularization and excellent results after stenting, the patient showed persistently elevated troponin levels.

Early but not late stent thrombosis is influenced by residual platelet aggregation in patients undergoing coronary interventions.

Aims: Recent studies suggest a relevant association of post-interventional residual platelet aggregation (RPA) under therapy with oral platelet inhibitors and the occurrence of atherothrombotic events. The influence of post-interventional RPA on the incidence of stent thrombosis (ST) has not been sufficiently evaluated in consecutive unselected cohorts of percutaneous coronary intervention (PCI) patients. The aim of this observational study was to investigate the impact of RPA on the incidence of ST within 3 months in patients treated with dual antiplatelet therapy.

Effect of comedication with proton pump inhibitors (PPIs) on post-interventional residual platelet aggregation in patients undergoing coronary stenting treated by dual antiplatelet therapy.

Introduction: Currently, there is an intense debate about whether comedication with proton pump inhibitors (PPIs) weakens the antiplatelet effect of clopidogrel in patients undergoing coronary stent implantation. Competing mechanisms on the hepatic cytochrome 2C19 level are proposed. The aim of this study was to assess the impact of PPI treatment on clopidogrel response by measuring the ex vivo platelet aggregation in patients with coronary intervention.

Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke.

Background And Purpose: Platelet collagen receptor glycoprotein VI (GPVI) contributes significantly to platelet adhesion and thrombus formation. We aimed to investigate GPVI in patients presenting with symptoms of acute cerebrovascular disease and to define GPVI as biomarker for acute stroke.

Methods: We consecutively evaluated 205 patients, who admitted the stroke unit with symptoms for stroke.