European heart journal
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European heart journal · Jun 2012
ReviewAntisense oligonucleotides for the treatment of dyslipidaemia.
Antisense oligonucleotides (ASOs) are short synthetic analogues of natural nucleic acids designed to specifically bind to a target messenger RNA (mRNA) by Watson-Crick hybridization, inducing selective degradation of the mRNA or prohibiting translation of the selected mRNA into protein. Antisense technology has the ability to inhibit unique targets with high specificity and can be used to inhibit synthesis of a wide range of proteins that could influence lipoprotein levels and other targets. A number of different classes of antisense agents are under development. ⋯ Other targets currently being addressed include apoC-III and apo(a) or Lp(a). By directly inhibiting the synthesis of specific proteins, ASO technology offers a promising new approach to influence the metabolism of lipids and to control lipoprotein levels. Its application to a wide variety of potential targets can be expected if these agents prove to be clinically safe and effective.
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European heart journal · May 2012
ReviewThe human sympathetic nervous system: its relevance in hypertension and heart failure.
Evidence assembled in this review indicates that sympathetic nervous system dysfunction is crucial in the development of heart failure and essential hypertension. This takes the form of persistent and adverse activation of sympathetic outflows to the heart and kidneys in both conditions. An important goal for clinical scientists is translation of the knowledge of pathophysiology, such as this, into better treatment for patients. ⋯ Despite the general importance of the sympathetic nervous system in blood pressure regulation, and the specific demonstration that the blood pressure elevation in essential hypertension is commonly initiated and sustained by sympathetic nervous activation, drugs antagonizing this system are currently underutilized in the care of patients with hypertension. Use of beta-adrenergic blocking drugs is waning, given the propensity of this drug class to have adverse metabolic effects, including predisposition to diabetes development. The blood pressure lowering achieved with carotid baroreceptor stimulation and with the renal denervation device affirms the importance of the sympathetic nervous system in hypertension pathogenesis, and perhaps suggests a wider role for anti-adrenergic antihypertensives, such as the imidazoline drug class (moxonidine, rilmenidine) which act within the CNS to inhibit central sympathetic outflow, although the lack of large-scale outcome trials with this drug class remains a very material deficiency.
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European heart journal · May 2012
Review Meta Analysis Comparative StudyOff-pump vs. on-pump coronary artery bypass surgery: an updated meta-analysis and meta-regression of randomized trials.
The benefits of off-pump coronary artery bypass (OPCAB) continue to be debated, in part due to the fact that pooled effects fail to consider differences in trial and patient characteristics. We sought to analyse the contemporary evidence for OPCAB vs. conventional coronary artery bypass (CCAB), incorporating recent larger trials, and adjusting for differences in trials using a technique known as meta-regression. ⋯ Our meta-analysis incorporating recent trials suggests that there appears to be a beneficial effect of OPCAB on stroke. Moreover, our meta-regression does not support the hypothesis that differences in study populations are responsible for the observed outcomes, although pooled individual patient-data would be better suited to confirm these findings.
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European heart journal · Mar 2012
ReviewHigh-sensitive troponin T measurements: what do we gain and what are the challenges?
Cardiac troponin (cTn) I and T are structural proteins unique to the heart. Detection of cTn in peripheral blood indicates cardiomyocyte damage. As acute myocardial infarction (AMI) is the most important cause of cardiomyocyte damage, cTns have become an integral part in the diagnosis of AMI. ⋯ The terms 'troponin-positive' and 'troponin negative' should therefore be avoided. 'Detectable' levels will become the norm and will have to be differentiated from 'elevated' levels. The differential diagnosis of a small amount of cardiomyocyte damage and therefore minor elevations of cTn is broad and includes acute and chronic cardiac disorders. The differential diagnosis of larger amount of injury and therefore more substantial elevations of cTn is largely restricted to AMI, myocarditis, and a rare patient with tako-tsubo cardiomyopathy.
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European heart journal · Mar 2012
ReviewSecondary stroke prevention: patent foramen ovale, aortic plaque, and carotid stenosis.
Stroke is the most debilitating cardiovascular event. It has a variety of causes that may be present simultaneously. In young or otherwise healthy people, the search for a patent foramen ovale (PFO) has become standard. ⋯ Statins can prevent progression of such plaques. Antiplatelet agents in asymptomatic and surgical endarterectomy in symptomatic patients or highly ulcerated lesions are the treatment of choice. Stenting with protection devices was shown competitive in selected patients.