Influence of diabetes on mortality in acute myocardial infarction: Data from the GISSI-2 study

AbstractObjectives. This study was conducted to determine the role of insulin-dependent and noninsulin-dependent diabetes in the prognosis of patients after myocardial infarction and treatment with fibrinolytic agents.Background. Several studies have shown that diabetic patients have a high mortality rate after acute myocardial infarction. However, the impact of diabetes on survival in patients treated with fibrinolytic agents is still undefined. It is also not known whether the type of diabetes or gender affects prognosis.Methods. We analyzed prevalence and prognostic significance of a history of diabetes in patients enrolled in the GISSI-2 study, all of whom received fibrinolytic agents. The incidence of deaths in the hospital and at 6 months after study entry was computed for patients without diabetes and for insulin-dependent and noninsulin-dependent diabetic patients; relative risks were evaluated by univariate and multivariate analysis.Results. Information on diabetic status was available for 11,667 patients, 94.2% of those randomized in the GISSI-2 study. The prevalence of diabetes was higher in women than in men (8.75% vs. 1.85%, p < 0.01 for insulin-dependent and 23.7% vs. 13.8%, p < 0.01 for noninsulin-dependent diabetic patients). The type of fibrinolytic agent did not affect mortality rates; the increase in in-hospital mortality of diabetic patients was moderate and similar for men with insulin- and noninsulin-dependent diabetes (8.7% and 10.1%, respectively, vs. 5.8% in nondiabetic patients); in women, mortality was markedly higher for insulin-dependent and only slightly higher for noninsulin-dependent diabetic patients (24.0% and 15.8%, respectively, vs. 13.9% for nondiabetic patients). The adjusted relative risks were 1.9 (95% confidence interval 1.2 to 2.9) for insulin-dependent diabetic women and 1.4 (95% confidence interval 1.1 to 1.8) for noninsulin-dependent diabetic men. The mortality rate after discharge showed a similar gender difference, and in insulin-dependent diabetic women, prognosis was ominous even in the absence of left ventricular damage before discharge.Conclusion. A history of diabetes is associated with a worse prognosis after myocardial infarction, even in patients treated with fibrinolytic agents. Gender and type of diabetes appear to be critical in affecting survival. In men, both insulin-dependent and noninsulin-dependent diabetes are associated with a moderately higher mortality rate; in women, insulin-dependent diabetes is, in itself, a strong risk factor for death after myocardial infarction

Frequency of predischarge ventricular arrhythmias in postmyocardial infarction patients depends on residual left ventricular pump performance and is independent of the occurrence of acute reperfusion

AbstractObjective. To test whether acute reperfusion of the infarct-related vessel after an acute myocardial infarction is associated with a subsequent reduction in spontaneous ventricular arrhythmias that is independent of ventricular ejection fraction, 1,944 patients from the GISSI-2 study population were studied. The patients were selected on the basis of a first myocardial infarction and the availability of two-dimensional echocardiographic ejection fraction and data on the number of premature ventricular contractions per hour on Holter monitoring.Background. It has been suggested that postthrombolytic reperfusion of the culprit vessel may be associated with an increased electrical stability of the infarcted heart, irrespective of its residual pump performance.Methods. The predischarge relation between ejection fraction and number of premature ventricular contractions per hour was plotted according to the occurrence (1,309 ptients) or not (635 patients) of acute reperfusion, identified noninvasively according to the modifications of the ST segment in serial electrocardiograms obtained in the first 24 h after infarction.Results. The frequency of premature ventricular contractions increased in a linear fashion with decreasing ejection fraction in both cohorts (p < 0.005 and p < 0.0001); however, there was no significant difference between the slops and the intercepts of the two regression lines, so that the relation between ejection fraction and number of premature ventricular contractions per hour could be adequately described by a single equation: y (number of premature ventricular contractions) = 33.0 - 0.42x (ejection fraction) (r = −0.107, p < 0.0001). The results were the same even when differences between group characteristics were accounted for in a multiple regression model.Conclusions. It is concluded that 1) the number of premature ventricular contractions per hour after an acute myocardial infarction is dependent in a linear, inverse fashion on the residual ventricular ejection fraction, and 2) this relation is independent of the occurrence of reperfusion in the acute phase of infarction

Predictors of nonfetal reinfarction in survivors of myocardial infarction after thrombolysis Results of the gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) data base

AbstractObjectives. This study was designed to reassess the prediction of recurrent nonfatal myocardial infarction in patients recovering from acute myocardial infarction after thrombolysis.Background. Recurrent nonfatal myocardial infarction is a strong and independent predictor of subsequent mortality. Current knowledge of risk factors for nonfatal reinfarction is still largely based on data gathered before the advent of thrombolysis. Thus, this prospective study was planned to identify harbingers of nonfatal reinfarction in the postinfarction patients of the multicenter Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial.Methods. Predictors of nonfatal reinfarction at 6 months were analyzed by multivariate technique (Cox model) in 8,907 GISSI-2 survivors of myocardial infarction with clinical follow-up, relying on a set of prespecified variables reflecting residual ischemia, left ventricular failure or dysfunction, complex ventricular arrhythmias, comorbidity as well as demographic and historical factors.Results. The postdischarge to 6-month incidence rate of nonfetal reinfarction was 2.5%. Independent predictors of nonfatal reinfarction were cardiac ineligibility for exercise test (relative risk 2.97, 95% confidence interval [CI] 1.98 to 4.45), previous myocardial infarction (relative risk 1.70, 95% CI 1.22 to 2.36) and angina at follow-up (relative risk 1.50, 95% CI 1.10 to 2.04). On further multivariate analysis, performed in 6,580 patients with both echocardiographic and electrocardiographic monitoring data available, a history of angina emerged as an additional risk predictor (relative risk 1.58, 95% CI 1.10 to 2.25).Conclusions. The 6-month incidence of nonfatal reinfarction is rather low in survivors of myocardial infarction after thrombolysis. Cardiac ineligibility for exercise testing and a history of coronary artery disease are risk predictors. Recurrent nonfatal infarction is not predictable by qualitative variables reflecting residual ischemia, except by postdischarge angina. Prediction of nonfatal reinfarction appears less accurate than prediction of mortality, as almost 50% of reinfarctions occur in patients without any of the identified risk factors

Adiponectin gene polymorphisms and their effect on the risk of myocardial infarction and type 2 diabetes: an association study in an Italian population.

Objective: While many studies have shown an association between the gene coding for adiponectin (ADIPOQ) and adiponectin levels, much more controversy surrounds its association with metabolic traits such as insulin resistance, obesity and type 2 diabetes. Furthermore, very few studies have looked into the relations between ADIPOQ variants and risk of cardiovascular disease. The present study assessed the influence of four common ADIPOQ Single Nucleotide Polymorphisms (SNPs), rs17300539 (-11391G→A), rs266729 (-11377C→G), rs2241766 (+45T→G) and rs1501299 (+276G→T) on the risk of myocardial infarction and type 2 diabetes. Methods and Results: A large genetic association case-control study was conducted in 2008 Italians, including patients with myocardial infarction, type 2 diabetes, or both, and a reference group of healthy controls. Homozygotes TT for the rs1501299 (+276) had half the risk of either myocardial infarction alone or in association with type 2 diabetes when compared to the carriers of the G allele (OR = 0.58, p =0.01, and OR = 0.55, p =0.006 respectively). SNPs rs17300539 (-11391), rs266729 (-11377) and rs2241766 (+45) showed no significant association with any of the three case groups. Conclusions: These results suggest that homozygotes TT for the adiponectin polymorphism rs1501299 (+276) are protected from the risk of myocardial infarction

Thromboembolic event rate in paroxysmal and persistent atrial fibrillation: Data from the GISSI-AF trial

BACKGROUND: Few data on the thromboembolic (TE) risk of paroxysmal and persistent atrial fibrillation (AF) are available. This study aimed to assess the incidence of TE events in paroxysmal and persistent AF. METHODS: We performed a subset post hoc analysis of 771 patients with paroxysmal and 463 with persistent AF enrolled in the multicenter, prospective, randomized, double-blind, placebo-controlled GISSI-AF trial - comparing the efficacy of valsartan versus placebo in preventing AF recurrences – where the choice of antithrombotic treatment was left to the judgment of the referring physician. TE and major outcome events were centrally validated. AF recurrences were detected by frequent clinic visits and a transtelephonic monitoring device with weekly and symptomatic transmissions. RESULTS: Eighty-five percent of patients had a history of hypertension, and the 7.7% had heart failure, left ventricular dysfunction, or both. The mean CHADS(2) score was 1.41±0.84. TE and major bleeding events were observed at a low incidence among the overall population at 1-year follow-up (0.97% and 0.81%, respectively). The univariate and multivariable analyses revealed no statistically significant differences in the incidence of TE, major bleeding events or mortality in paroxysmal and persistent AF patients. TE events were more common among women than men (p=0.02). The follow-up examination showed under- or overtreatment with warfarin in many patients, according to guideline suggestions. Warfarin was more frequently prescribed to patients with persistent AF (p<0.0001) and patients with AF recurrences (p<0.0001). AF recurrences were noninvasively detected in 632 (51.2%) patients. In patients without AF recurrences, the TE event rate was 0.5% versus 1.74%, 1.28%, and 1.18% for those with only symptomatic, only asymptomatic or both symptomatic and asymptomatic AF recurrences, respectively, but the difference was not statistically significant, even after adjusting for warfarin treatment and the CHADS(2) score (HR 2.93; CI 95%; 0.8-10.9; p=0.11). CONCLUSIONS: TE and major bleeding events showed a very low incidence in the GISSI-AF trial population, despite under- or overtreatment with warfarin in many patients. TE events had a similar rate in paroxysmal and persistent AF. TRIAL REGISTRATION: Trial registration number: NCT0037627

Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17

Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size λ(sib) > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies

Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials

Background Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. Methods We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134 537) and five trials of more-intensive versus less-intensive statin therapy (n=39 612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1·0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. Findings 46 675 (27%) of 174 149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1·1 mmol/L in statin vs control trials and roughly 0·5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1·0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0·84, 99% CI 0·78–0·91) and men (RR 0·78, 99% CI 0·75–0·81, adjusted p value for heterogeneity by sex=0·33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0·11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0·91, 99% CI 0·84–0·99) and men (RR 0·90, 99% CI 0·86–0·95; adjusted heterogeneity p=0·43). Interpretation In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events.UK Medical Research Council, British Heart Foundation, Australian National Health and Medical Research Council, European Community Biomed Program

Anaesthesiological strategies in elective craniotomy: randomized, equivalence, open trial – The NeuroMorfeo trial

<p>Abstract</p> <p>Background</p> <p>Many studies have attempted to determine the <it>"best" </it>anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaestesiological strategy depends only on the anaesthetists' preferences or institutional policies.</p> <p>This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures.</p> <p>Methods/Design</p> <p>NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score ≥ 9 (primary end-point). Two statistical comparisons have been planned:</p> <p>1) sevoflurane + fentanyl vs. propofol + remifentanil;</p> <p>2) sevoflurane + remifentanil vs. propofol + remifentanil.</p> <p>Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia; intraoperative adverse events; evaluation of surgical field; postoperative adverse events; patient's satisfaction and analysis of costs.</p> <p>411 patients will be recruited in 14 Italian centers during an 18-month period.</p> <p>Discussion</p> <p>We presented the development phase of this anaesthesiological on-going trial. The recruitment started December 4^th, 2007 and up to 4^th, December 2008, 314 patients have been enrolled.</p

Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke

Genetic factors have been implicated in stroke risk but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) in ischemic stroke and its subtypes in 3,548 cases and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 cases and 6,281 controls. We replicated reported associations between variants close to PITX2 and ZFHX3 with cardioembolic stroke, and a 9p21 locus with large vessel stroke. We identified a novel association for a SNP within the histone deacetylase 9(HDAC9) gene on chromosome 7p21.1 which was associated with large vessel stroke including additional replication in a further 735 cases and 28583 controls (rs11984041, combined P = 1.87×10−11, OR=1.42 (95% CI) 1.28-1.57). All four loci exhibit evidence for heterogeneity of effect across the stroke subtypes, with some, and possibly all, affecting risk for only one subtype. This suggests differing genetic architectures for different stroke subtypes