Serdar Farhan

Complementary role of copeptin and high‐sensitivity troponin in predicting outcome in patients with stable chronic heart failure

Copeptin, the C‐terminal part of the vasopressin pro‐hormone, is elevated after myocardial infarction and predicts adverse outcome. In the present study we investigated whether the complementary role of copeptin and cardiac troponin T (cTnT) could be used for identification of high‐risk patients with chronic stable heart failure.

Impact of concomitant treatment with proton pump inhibitors and clopidogrel on clinical outcome in patients after coronary stent implantation

The aim of the study was to evaluate the effect of the concomitant treatment with proton-pump inhibitors (PPIs) and clopidogrel on the incidence of stent thrombosis, acute coronary syndrome (ACS) and death in patients who underwent percutaneous coronary intervention (PCI) and stent implantation. In total, 1,210 patients under dual antiplatelet therapy, who underwent PCI and stent implantation, were included in a prospective registry from January 2003 until December 2006. The patients were divided retrospectively into those with or without long-term PPI treatment (for the duration of dual antiplatelet therapy). All-cause mortality, cardiovascular death, re-hospitalisation for re-ACS, stent thrombosis, as well as the combined endpoint all-cause death, re-ACS or stent thrombosis were evaluated over a mean follow-up period of 7.8 (± 3.63) months (range 1-12 months). Propensity score analysis was performed to reduce potential selection bias and exhibited no significant difference between the two study groups with respect to all-cause mortality, cardiovascular death, re-ACS, stent thrombosis and the combined endpoint. In pre-specified subgroup analyses performed in patients presenting with ACS and referred for acute PCI or for stable patients referred for elective PCI, receiving drug-eluting stents or bare metal stents, in diabetics or non-diabetics, in males or females, and in patients older than 75 years or ≤75 years of age use of PPIs had no significant impact on clinical outcome. Our data suggest that a combined use of clopidogrel as part of dual antiplatelet therapy (DAPT) after coronary stenting and PPIs does not significantly influence the clinical outcome.

Platelet function variability and non-genetic causes

Dual antiplatelet therapy (DAPT) has been established for the treatment of coronary artery disease, especially in and after acute coronary syndromes, and after coronary interventions. Data suggest that a significant percentage of individuals treated with clopidogrel do not receive the expected therapeutic benefit because of a decreased responsiveness of their platelets, which is caused by several extrinsic and intrinsic mechanisms. The clinical consequence of clopidogrel non-responsiveness is severe cardiovascular complications. Besides genetic variability in response to antiplatelet therapy, non-genetic causes such as drug interactions (proton-pump inhibitors, statins, calcium-channel blockers, coumarin derivates, antibiotics, antimycotics) and co-morbidities (diabetes mellitus, renal failure, obesity) are responsible for this phenomenon. Large clinical trials with standardised laboratory methods and hard clinical endpoints are needed to identify these interactions with clopidogrel and predictors for its non-responsiveness.

Soluble ST2 and Interleukin-33 Levels in Coronary Artery Disease: Relation to Disease Activity and Adverse Outcome

Objectives ST2 is a receptor for interleukin (IL)-33. We investigated an association of soluble ST2 (sST2) and IL-33 serum levels with different clinical stages of coronary artery disease. We assessed the predictive value of sST2 and IL-33 in patients with stable angina, non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI). Methods We included 373 patients of whom 178 had stable angina, 97 had NSTEMI, and 98 had STEMI. Patients were followed for a mean of 43 months. The control group consisted of 65 individuals without significant stenosis on coronary angiography. Serum levels of sST2 and IL-33 were measured by ELISAs. Results sST2 levels were significantly increased in patients with STEMI as compared to patients with NSTEMI and stable angina as well as with controls. IL-33 levels did not differ between the four groups. During follow-up, 37 (10%) patients died and the combined endpoint (all cause death, MI and rehospitalisation for cardiac causes) occurred in 66 (17.6%) patients. sST2 serum levels significantly predicted mortality in the total cohort. When patients were stratified according to their clinical presentation, the highest quintile of sST2 significantly predicted mortality in patients with STEMI, but not with NSTEMI or stable coronary artery disease. sST2 was a significant predictor for the combined endpoint in STEMI patients and in patients with stable angina. Serum levels of IL-33 were not associated with clinical outcome in the total cohort, but the highest quintile of IL-33 predicted mortality in patients with STEMI. Conclusions Serum levels of sST2 are increased in patients with acute coronary syndromes as compared to levels in patients with stable coronary artery disease and in individuals without coronary artery disease. sST2 and IL-33 were associated with mortality in patients with STEMI but not in patients with NSTEMI or stable angina.

Fibrinolytic dysfunction in insulin-resistant women with previous gestational diabetes

Background  Women with a history of gestational diabetes (p‐GDM) are at increased risk of developing type 2 diabetes mellitus (DM2) later in life, and therefore at increased risk for future cardiovascular disease.

New anticoagulant agents in acute coronary syndromes

In the development of new antithrombotic drugs the main target has become the improvement of the net clinical benefit (reduction of major bleeding complications as well as reduction of thromboembolic ischaemic complications), rather than a higher efficacy in terms of reduction of thromboembolic ischaemic events only.1 Standard antithrombin treatment of non-ST elevation acute coronary syndromes (NSTE-ACS) in recent years has consisted of unfractionated heparin (UFH) or low molecular weight heparin (LMWH), especially enoxaparin, which has been tested most extensively within this group of agents.w1 w2 In patients with ST elevation myocardial infarction (STEMI) the use of UFH is still the major antithrombotic regimen when primary percutaneous coronary intervention (PCI) is performed. As an adjunct antithrombin to thrombolytic therapy, enoxaparin has been proven to be more efficacious than UFH, with comparable bleeding rates, and is widely used.w3 In the past few years, new antithrombins have been investigated in patients with acute coronary syndromes (ACS). Based on favourable data obtained from large prospective randomised clinical trials, the indirect anti-Xa inhibitor fondaparinux, as well as the direct thrombin inhibitor bivalirudin, have made it into the updated guidelines of the American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) (tables 1 and 2).1–5 Moreover, new direct anti-Xa inhibitors such as apixaban, rivaroxaban, and otamixaban, as well as the direct antithrombin dabigatran, are still under clinical investigation, and the results of phase II dose finding and safety studies have been published recently. View this table: Table 1 Comparison between European and American guidelines for the antithrombotic management of patients with non-ST elevation acute coronary syndromes View this table: Table 2 American guidelines for antithrombotic management in patients with ST elevation myocardial infarction Figure 1 shows the onset of action of the different antithrombins in the coagulation cascade. This article provides an overview of the results …

Levels of fetuin‐A relate to the levels of bone turnover biomarkers in male and female patients with type 2 diabetes

Objective  To evaluate the relationship of plasma fetuin‐A levels with markers of bone turnover in male and female type 2 diabetic subjects.

Sex-related differences in baseline characteristics, management and outcome in patients with acute coronary syndrome without ST-segment elevation.

Aim: To detect sex-related differences in baseline characteristics, management and outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Methods: Data from 812 consecutive patients admitted to our cardiology department for NSTE-ACS between 2001 and 2004 were obtained. Early invasive therapy was defined as revascularization during first hospital stay. A seven-year follow-up for the clinical endpoint of all-cause mortality could be obtained in 342 women and 440 men, respectively. Results: Compared with men, women were significantly older and more likely to suffer from renal insufficiency. The proportion treated with clopidogrel at admission was 43.6% for women and 52.7% for men, respectively (p=0.011). Significantly fewer women underwent an early invasive therapy compared with men (27.5% vs. 35.2%; p=0.021). Age and renal insufficiency were the strongest predictors for a conservative approach in both female and male patients. After adjustment for baseline characteristics there was no significant difference in treatment between women and men (odds ratio 0.89; 95% confidence interval 0.59–1.35; p=0.588). While in-hospital mortality was similar between the sexes, long-term mortality was significantly higher in women compared with men (8.2% vs. 7.0%; p=0.549 for in-hospital mortality and 54.8% vs. 39.3%; p<0.001 for seven-year mortality). However, after adjustment for baseline characteristics and treatment there was no significant difference in long-term mortality between women and men (hazard ratio 1.14; 95% confidence interval 0.89–1.47; p=0.307). Conclusion: In these patients with NSTE-ACS women were less likely to undergo an early invasive therapy compared with men due to their higher age and the higher rate of renal insufficiency. After adjustment for age, comorbidities and treatment female sex was not associated with worse long-term outcome.

Implantation of paclitaxel-eluting stent impairs the vascular compliance of arteries in porcine coronary stenting model.

BACKGROUND The impaired compliance of large and medium-sized muscular arteries has been shown to correlate with the risk of adverse cardiovascular events. We assessed coronary artery distensibility using simultaneous intracoronary ultrasound and pressure wire measurements in porcine coronary arteries after implantation of paclitaxel-eluting (PES) and bare metal stents (BMS) and compared this with the histopathology of the arterial wall injury. METHODS PES and BMS were implanted into porcine left coronary arteries under general anesthesia. At 1-month follow-up (FUP) the endothelium-dependent and endothelium-independent vascular compliances were measured after intracoronary infusion of 10(-6)M acetylcholine for 2.5min, and intracoronary bolus of 100microg nitroglycerine, respectively. The arterial stiffness index, distensibility and reflexion index were calculated in stented arteries (n=25 PES and n=25 BMS), and correlated with histopathologic and histomorphometric changes of the vessel wall. RESULTS In spite of smaller neointimal area, the fibrin deposition, medial thickening, vascular wall inflammation scores and arterial remodeling index were elevated and endothelialization was impaired in arteries with PES. Arteries with PES exhibited significantly worse endothelium-dependent vascular compliance: the stiffness (p<0.001) and reflexion index (p<0.001) were significantly higher and the distensibility index (p<0.001) lower as compared with the arteries with BMS. The endothelium-independent vascular reaction was similarly impaired in arteries with PES, as the stiffness index (p<0.001) and the distensibility index (p<0.001) differed significantly between the PES and BMS groups. Incomplete endothelialization (r=0.617, p<0.001) was significantly associated with the endothelium-dependent increased vascular stiffness. The increased fibrin score (r=0.646, p<0.001), vessel wall inflammation (r=0.657, p<0.001) and medial thickening (r=0.672, p<0.001) correlated significantly with the endothelium-independent stiffness index. CONCLUSIONS Implantation of PES impairs the coronary artery wall structure and the endothelium-dependent and independent vessel wall dynamics more than does the implantation of BMS.

An increase of interleukin-33 serum levels after coronary stent implantation is associated with coronary in-stent restenosis

Highlights • An association between IL-33 and restenosis in coronary artery disease exists.• IL-33 increase after stent implantation is associated with a higher rate of restenosis.• IL-33 estimation before and after PCI could determine patients at risk.