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De Mulder M.,Medical Center Alkmaar | Umans V.A.,Medical Center Alkmaar | Cornel J.H.,Medical Center Alkmaar | Van Der Zant F.M.,Medical Center Alkmaar | And 5 more authors.
JAMA Internal Medicine | Year: 2013

IMPORTANCE: Elevated plasma glucose levels in patients with acute coronary syndrome (ACS) on hospital admission are associated with increased mortality. Clinical trials of glucose regulation have provided inconsistent results with respect to cardiovascular outcomes, perhaps because target glucose levels have been suboptimal. OBJECTIVE: To study the effectiveness and safety of intensive glucose management in patients with ACS who have hyperglycemia, aiming at strict blood glucose normalization. DESIGN, SETTING, AND PARTICIPANTS: Single-center, prospective, open-label, randomized clinical trial in a large teaching hospital. Patients with ACS with an admission plasma glucose level of 140 to 288 mg/dL were eligible for inclusion and enrolled from July 23, 2008, to February 8, 2012. Patients with insulin-dependent diabetes mellitus were excluded. Informed consent was obtained from 294 patients, who were randomized. Of these, 93.6%received percutaneous coronary intervention (PCI). INTERVENTIONS: Intensive glucose management strategy, aiming at a plasma glucose level of 85 to 110 mg/dL by using intravenous insulin, or to conventional expectative glucose management. MAIN OUTCOMES AND MEASURES: End points were assessed according to the intention-to-treat principle. The primary end point was high-sensitivity troponin T value 72 hours after admission (hsTropT72); secondary end points, area under the curve of creatine kinase,myocardial band (AUC-CK-MB), release and myocardial perfusion scintigraphy findings at 6 weeks' follow-up. RESULTS: In the intensive management arm, median hsTropT72 was 1197 ng/L (25th and 75th percentiles of distribution, 541-2296 ng/L) vs 1354 ng/L (530-3057 ng/L) in the conventional arm (P = .41). Median AUC-CK-MB was 2372 U/L (1242-5004 U/L) vs 3171 U/L (1620-5337 U/L) (P = .18). The difference in median extent of myocardial injury measured by myocardial perfusion scintigraphy was not significant (2%vs 4%) (P = .07). Severe hypoglycemia (<50 mg/dL) was rare and occurred in 13 patients. Before discharge, death or a spontaneous second myocardial infarction occurred in 8 patients (5.7%) vs 1 (0.7%) (P = .04). CONCLUSIONS AND RELEVANCE: Intensive glucose regulation did not reduce infarct size in hyperglycemic patients with ACS treated with PCI, and was associated with harm. Future studies should focus on patients with ACS who have persistently elevated blood glucose after PCI, and should evaluate alternative strategies for optimizing glycemia. TRIAL REGISTRATION www.trialregister.nl Identifier: NTR1205 Copyright 2013 American Medical Association. All rights reserved. Source

Groenveld H.F.,University of Groningen | Tijssen J.G.P.,University of Amsterdam | Tijssen J.G.P.,Interuniversity Cardiology Institute Netherlands | Crijns H.J.G.M.,Maastricht University | And 6 more authors.
Journal of the American College of Cardiology | Year: 2013

Objectives: This study sought to investigate differences in outcome between patients treated with successful strict, failed strict, and lenient rate control. Background: The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation) study showed no difference in outcome between lenient and strict rate control in patients with permanent atrial fibrillation (AF). However, in the strict group not all patients achieved the pre-defined heart rate target. Methods: The primary outcome was a composite of cardiovascular morbidity and mortality. For the current analysis outcome events were analyzed from end of the dose-adjustment phase until end of follow-up (median 2.9 years [interquartile range: 2.4 to 3.0 years]). Of 614 patients, 608 completed the dose-adjustment phase - 301 in the strict (resting heart rate <80 beats/min, and during moderate exercise <110 beats/min) and 307 in the lenient group (resting heart rate <110 beats/min). In the strict group, 203 of 301 patients achieved the rate control target, and 98 failed. Results: Heart rate was different after the dose-adjustment phase between the successful strict (72 ± 7 beats/min), failed strict (86 ± 14 beats/min), and lenient (93 ± 8 beats/min) group (p < 0.001) and remained significantly different during follow-up. The primary outcome was reached in 27 of 203 (14.2% KM estimate) in the successful strict versus 14 of 98 (15%) in the failed strict versus 35 of 307 (12.1%) in the lenient group (p = 0.5). The components of the primary outcome and quality of life were similar in the groups. Conclusions: In patients with permanent AF, successful strict rate control does not improve outcome. Therefore, lenient rate control might be frontline therapy. © 2013 American College of Cardiology Foundation. Source

Salic K.,Maastricht University | Salic K.,Interuniversity Cardiology Institute Netherlands | De Windt L.J.,Maastricht University
Current Atherosclerosis Reports | Year: 2012

MicroRNAs (miRs) are short non-coding RNA molecules involved in post-transcriptional gene regulation by binding to the 3' untranslated region of a messenger RNA (mRNA), thereby inhibiting the translation or inducing mRNA destabilization. MiRs are generally considered to act as intracellular mediators essential for normal cardiac function, and their deregulated expression profiles have been associated with cardiovascular diseases. Recent studies have revealed the existence of freely circulating miRs in human peripheral blood, which are present in a stable nature. This has raised the possibility that miRs may be released in the circulation and can serve as novel diagnostic markers for acute or chronic human disorders, including myocardial infarction (MI). This review summarizes the recent findings of miRs that fulfill the criteria of candidate biomarkers for MI. © The Author(s) 2012. Source

Van Aelst L.N.L.,Catholic University of Leuven | Van Aelst L.N.L.,University Hospitals Leuven | Heymans S.,Catholic University of Leuven | Heymans S.,Maastricht University | And 2 more authors.
Journal of Cardiovascular Translational Research | Year: 2013

MicroRNAs (miRs) are short, noncoding RNAs that function as posttranscriptional inhibitors of mRNA translation to protein. They are essential for normal development and homeostasis. Dysregulated expression patterns both cause and result from disease states. Generally studied as intracellular mediators, miRs can be isolated from body fluids and exhibit remarkable stability to degradation. These features, in combination with their tissue specificity, make miRs attractive candidates as blood-derived biomarkers for coronary artery disease (CAD), the most frequent cause of death worldwide. The use of miRs as biomarkers in both symptomatic and asymptomatic CAD and the influence of conventional cardiovascular risk factors and CAD treatment on their circulating levels are the topics of this review. To conclude, it highlights the remaining hurdles to tackle before this promising application of miRs can enter into routine clinical practice. © 2013 Springer Science+Business Media New York. Source

De Mulder M.,Medical Center Alkmaar | Oemrawsingh R.M.,Erasmus University Rotterdam | Oemrawsingh R.M.,Interuniversity Cardiology Institute Netherlands | Stam F.,Medical Center Alkmaar | And 2 more authors.
Heart | Year: 2012

Background: Elevated plasma glucose levels on admission (APG) are very common in patients with acute coronary syndrome (ACS) and can be the first indication of diabetes mellitus. Objective: To provide insight into the prevalence of previously undiagnosed diabetes and to compare different methods of diagnosing diabetes in patients with ACS. Methods: Patients with ACS with elevated APG who participated in the BIOMArCS 2 glucose trial underwent an oral glucose tolerance test (OGTT) prior to discharge. 130 patients were included who underwent metabolic assessment. Of these, 109 had an OGTT and 13 patients had pre-existing diabetes. Results: The OGTT results were categorised as (previously) undiagnosed diabetes in 35% of patients (fasting plasma glucose (FPG) ≥7.0 mmol/l or 2-h post-load glucose ≥11.1 mmol/l) and impaired glucose metabolism in 44% (FPG 6.1-6.9 mmol/l or post-load glucose 7.8-11.0 mmol/l), so only 21% had a normal glucose metabolism. Undiagnosed diabetes could not be adequately predicted with APG, FPG or HbA1c (area under the ROC curve 0.61, 0.75 and 0.72, respectively). Patients with abnormal glucose metabolism were significantly older, had higher admission HbA1c values, a higher Killip classification and more often had a prior stroke than patients with normal glucose metabolism. Conclusion: 79% of hyperglycaemic patients with ACS were found to have abnormal glucose metabolism. As APG, HbA1c and FPG had a low sensitivity to detect undiagnosed diabetes, an OGTT appears to be the best test to assess the presence of previously undiagnosed diabetes or impaired glucose metabolism in hyperglycaemic patients with ACS. Source

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