Objectives To investigate whether statins reduce all cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus. Design Meta-analysis of randomised trials. Data sources Cochrane controlled trials register, Embase, and Medline. Data abstraction Two independent investigators identified studies on the clinical effects of statins compared with a placebo or control group and with followup of at least one year, at least 80% or more participants without established cardiovascular disease, and outcome data on mortality and major cardiovascular disease events. Heterogeneity was assessed using the Q and I 2 statistics. Publication bias was assessed by visual examination of funnel plots and the Egger regression test. Results 10 trials enrolled a total of 70 388 people, of whom 23 681 (34%) were women and 16 078 (23%) had diabetes mellitus. Mean follow-up was 4.1 years. Treatment with statins significantly reduced the risk of all cause mortality (odds ratio 0.88, 95% confidence interval 0.81 to 0.96), major coronary events (0.70, 0.61 to0.81), and major cerebrovascular events (0.81, 0.71 to 0.93). No evidence of an increased risk of cancer was observed.

Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose, swine (13 VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of reperfusion. VNS was started 5 min prior to reperfusion and continued until 15 min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and infarct size (% of area at risk), circulating cytokines, and regional myocardial leukocyte influx were assessed after 120 min of reperfusion. VNS significantly reduced infarct size from 67 ± 2 % in sham to 54 ± 5 % and area of no-reflow from 54 ± 6 % in sham to 32 ± 6 %. These effects were accompanied by reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the infarct area (all p < 0.05), whereas systemic circulating plasma levels of TNFα and IL6 were not affected. The degree of cardioprotection could not be explained by the VNS-induced bradycardia or the VNS-induced decrease in the double product of heart rate and left ventricular systolic pressure. In the presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and area of no-reflow, which was paralleled by similarly unaffected regional leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive therapy that limits reperfusion injury in a large animal model of acute myocardial infarction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-015-0508-3) contains supplementary material, which is available to authorized users.

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp oronary heart disease (CHD) is the leading cause of death and disability worldwide and one of its major pathophysiological manifestations is acute myocardial infarction (AMI). Although percutaneous coronary intervention (PCI) remains the most effective treatment strategy in patients presenting with AMI, high-risk patients with severe CHD are being referred for coronary artery bypass grafting (CABG). With both forms of treatment, patients are subjected to acute ischemia-reperfusion injury (IRI) and despite the merits of PCI and CABG, mortality and morbidity in these patients remain significant. Thus, cardioprotective strategies further limiting IRI are of major clinical interest in these settings.Remote ischemic conditioning (RIC) represents a novel treatment strategy for limiting myocardial IRI by applying intermittent, sublethal episodes of ischemia and reperfusion to an organ or tissue distant from the heart. Experiments in a canine model by Przyklenk et al first demonstrated that brief ischemic episodes (4 times for 5 min followed by 5 min of reperfusion) of the left circumflex coronary artery significantly reduced myocardial infarct size following sustained occlusion of the left anterior descending coronary artery, that is, remote intracardiac conditioning.

During reperfusion, intracoronary adenosine can limit infarct size and no-reflow in a porcine model of acute myocardial infarction. However, protection was only observed when adenosine was administered via prolonged high-dose infusion, and not via short-acting bolus injection. These findings warrant reconsideration of adenosine as an adjuvant therapy during early reperfusion.