Tar yield of cigarettes and risk of acute myocardial infarction

Objective-To analyse the relation between tar and nicotine yield of cigarettes smoked in the recent past and the risk of myocardial infarction. Design-Multicentre case-control study conducted between September 1988 and June 1989. Setting-Over 80 coronary care units in various Italian regions. Subjects-916 patients with acute myocardial infarction without history of ischaemic heart disease and 1106 controls admitted to hospital for acute conditions not related to known or suspected risk factors for ischaemic heart disease. Main outcome measures-Relative risk of myocardial infarction according to type of cigarette smoked adjusted for identified potential confounding factors. Brands of cigarettes classified according to yield of tar and nicotine. Results-Patients with acute myocardial infarction were more often smokers and among smokers they tended to smoke more cigarettes. Compared with non-smokers their estimated relative risks were 3.8, 4.3, 3.2, and 3.7 in the four categories of tar yield ( 15-20, and > 20 mg, respectively). No trend in risk across yields was evident when analysis was restricted to smokers and allowance was made for number of cigarettes. Compared with risks in subjects in the lowest category of tar yield the relative risks were 1.2, 0.8, and 1.0 for the subsequent yields. Compared with risks in non-smokers the relative risks ranged from 9.3 to 12.6 below the age of 50 but no trend was observed with increasing yield. Conclusions-Changing to cigarettes with a lower tar yield is not an effective means of reducing tobacco related morbidity from myocardial infarction

Attributable risks for nonfatal myocardial infarction in Italy

Background. The proportions of nonfatal acute myocardial infarctions (AMI) in Italy attributable to cigarette smoking, body mass, serum cholesterol level, hypertension, diabetes, and family history of AMI (attributable risks, AR) were estimated using data from a case-control study on 614 incident cases of AMI before age 75 with no history of ischemic heart disease and 792 control subjects admitted to the same hospitals where cases were identified for acute, nonneoplastic, cardio- or cerebrovascular conditions not known or suspected to be related to cigarette smoking. Methods. The study was conducted between September 1988 and June 1989 within the framework of the GISSI-2 clinical trial. We assumed a multiplicative model and thus the risk attributable to several factors combined is not the sum of those attributable to the single factors. Results. Overall the AR of smoking was 49%, and for cholesterol, body mass, family history of AMI, hypertension, and diabetes the AR were 49, 16, 14, 13, and 6%, respectively. Together these factors explained 86% of AMI cases. Though differences emerged for each single factor, the proportion of AMI explained by the six factors together was approximately the same for both sexes, while these factors accounted for 97% of AMI cases before age 50 (and smoking alone for 70%) and for 80% after age 50. Conclusions. This study confirms that interventions on well-defined risk factors could, in principle, lead to the avoidance of the great majority of myocardial infarctions in this population (i.e., about 80% before age 75 and about 95% before age 50)

Restoration of blood 2,3-diphosphoglycerate levels in multi-transfused patients: effect of organic and inorganic phosphate

Blood stored in acid-citrate-dextrose (ACD) shows a progressive decrease in 2,3-diphosphoglycerate (DPG) content. Since the decrease in DPG increases hemoglobin oxygen affinity, which in turn may reduce tissue and venous PO2 and peripheral oxygen delivery, many efforts have been made to preserve or restore DPG levels in stored blood. An in vivo rejuvenating technique, employing fructose-1,6-diphosphate (FDP) at a mean dosage of 1 mmol kg-1 day-1 of phosphate, to increase the DPG circulating level in multi-transfused patients is proposed. Eighteen patients, who received at least one-third of their estimated blood volume (3990 +/- 480 (SEM) ml of ACD stored blood) in blood transfusion, were treated: nine with inorganic phosphate, and nine with FDP. Basal DPG was very low in both groups: 12.61 +/- 1.34 (SEM) and 10.42 +/- 0.98 (SEM) mumol g-1, respectively (normal value is 14.5 mumol g-1, at pH 7.40). However, DPG values increased significantly and promptly in patients receiving FDP, whereas in cases of inorganic phosphate administration, it was not significantly raised over the basal value until the third day. Phosphatemia remained normal and constant with FDP, but it rose significantly on the third day of treatment with inorganic phosphate. FDP appears to consistently and rapidly increase DPG levels after transfusion with blood stored in ACD, and to be particularly safe

Coffee consumption and risk of acute myocardial infarction in Italian males

The relationship between coffee consumption and acute myocardial infarction (AMI) was analyzed using data from a case-control study conducted in 1988 to 1989 within the framework of the GISSI-2 trial on streptokinase versus alteplase and heparin versus no heparin in the treatment of AMI. A total of 801 male patients with AMI and 792 control subjects who were hospitalized in several Italian regions for diseases unrelated to known or potential risk factors for cardiovascular diseases were included. Compared with coffee nondrinkers, the multivariate relative risks (RRs), after allowance for age, education, body mass index, smoking habits, alcohol consumption, family history of AMI, cholesterol level, history of diabetes, and hypertension, were 0.8 (95% confidence interval (CI), 0.5 to 1.2) for consumption of one cup/d, 1.3 (95% CI, 0.9 to 2.0) for two cups/d, 1.8 (95% CI, 1.1 to 2.7) for three cups, 2.5 (95% CI, 1.5 to 4.1) for four cups, and 2.6 (95% CI, 1.6 to 4.2) for five cups or more. The trend in risk with dose was statistically significant (P < 0.001). Duration of coffee consumption was not associated with the risk of AMI. The RRs for daily coffee consumption were elevated across strata of various covariates, including age, smoking habits, cholesterol level, diabetes, and hypertension, with a particularly elevated (although not significantly heterogeneous) estimate in patients younger than 50 years (RR, 5.7; 95% CI, 3.0 to 10.9 for four or more cups/d). The RR in patients who drank four or more cups of coffee per day and were current smokers was 8.1 (95% CI, 5.1 to 13.0), suggesting an unfavorable effect on the combination of cigarette smoking and high coffee intake on the risk of AMI

Knowledge extraction in a population suffering from heart failure

the prevalence of heart failure is 2-3% of the general population and affects millions of people. In recent years, considerable progress has been made decoding the pathophysiology of this multi-factorial trait. Still the search for new variables with significant impact on the development of heart failure is an ongoing process. As part of the VPH2 project, a data mining study was conducted aiming specifically at extracting new knowledge from a population suffering from heart failure In particular, the population consists of patients suffering from post-mitral infarction development of myocardial remodelling. The aim of the study was to apply data mining methodologies in order to classify the patients in those who developed late onset heart failure against those that did not develop the trait. Data derived from a multiple genetic variant analysis added predictive value to this study. The methodology followed, the results and the clinically important findings are presented in this work

Clinical predictors of atrial fibrillation recurrence in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation (GISSI-AF) trial

Background - Atrial fibrillation (AF) is a common arrhythmia that frequently recurs after restoration of sinus rhythm (SR). Identifying risk factors for recurrence may help define the best strategy for secondary prevention. Methods - The GISSI-AF trial enrolled 1,442 patients in SR with at least 2 documented AF episodes in the previous 6 months or after cardioversion in the last 2 weeks. Patients were randomized to valsartan or placebo; all other treatments for AF or underlying heart diseases were allowed. Primary end points were time to first recurrence of AF and proportion of patients with >1 AF episode during 1-year follow-up. We evaluated clinical and electrocardiographic baseline characteristics of all patients to identify independent predictors for AF recurrence using a Cox multivariable model. Results - Risk factors for AF recurrence were a history of 2 or more AF episodes in the previous 6 months, independent of the modality of SR restoration, spontaneous (HR 1.42, 95% CI 1.14-1.77, P = .002), or by cardioversion (HR 1.19, 95% CI 1.01-1.40, P = .038), and a lower heart rate during SR (HR 0.99, 95% CI 0.99-1.00, P = .052). The risk factors were the same for > 1 AF recurrence. Patients treated with amiodarone had a lower risk for both end points (P < .0001 and P = .017), whereas those on diuretics had a greater risk (P = .009 and P = .003). Conclusions - In the GISSI-AF study population, AF history had significant prognostic value independent of the modality of SR restoration. Amiodarone and diuretic treatment affected the rate of AF recurrence

Red blood cell oleic acid levels reflect olive oil intake while omega-3 levels reflect fish intake and the use of omega-3 acid ethyl esters: The Gruppo Italiano per lo Studio della Sopravvivenza nell&apos;Infarto Miocardico&#8211;Heart Failure trial

The Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico\u2013Heart Failure (GISSI-HF) study reported benefits of n-3 fatty acid (FA) treatment on cardiovascular (CV) events, but the effects of treatment on a putative CV disease risk factor, the red blood cell (RBC) n-3 FA level (the omega-3 index), have not been examined in this context. We hypothesized that treatment with prescription omega-3 acid ethyl esters (O3AEE) would increase the omega-3 index to the proposed cardioprotective value of 8%. RBCs were collected from a subset of patients participating in the GISSI-HF study (n=461 out of 6975 randomized), at baseline and after 3 months of treatment with either an olive oil placebo or O3AEE (1 g/d). RBC FA levels were expressed as a percentage of total FA. Patients also reported their typical olive oil and fish intakes. RBC oleic acid levels were directly correlated with reported frequency of olive oil consumption, and the omega-3 index was correlated with reported fish intake (P for trends &lt;0.001 for both). After treatment, the omega-3 index increased from 4.8\ub11.7% to 6.7\ub11.9% but was unchanged in the placebo group (4.7\ub11.7 to 4.8\ub11.5%) (P&lt;.0001 for changes between groups). At 3 months, more patients reached the proposed target omega-3 index level of 8%-12% in the treated vs placebo group (22.6% vs. 1.3%, P&lt;.0001), however, what omega-3 index levels were ultimately achieved after four years in this trial are unknown

Critical review of the quality and development of randomized clinical trials (RCTs) and their influence on the treatment of advanced epithelial ovarian cancer

Trials on chemotherapy of advanced ovarian cancer published between 1975-88 were systematically reviewed for quality (according to the method of Chalmers) and consistency of tested hypotheses with a view to a meta-analysis of all published studies in the field. Median overall, internal and external validity scores were 47%, 43% and 53%, respectively. No association was found between scores and key features of trials, such as percentage studies with significant results in response or survival or percentage studies with high or low follow-up retention (withdrawal rates less than or greater than or equal to 15%). Only 21% of trials reported a fully blind randomization procedure and only in 13% were drop-outs accounted for by the intent-to-treat method. Only 4 trials entered more than 150 patients per arm, a sample size consistent with detection of an absolute difference of 11% in mortality. The majority of trials (58%) investigated the role of combination regimens versus a single-agent control arm. The remaining trials tested different polychemotherapies. However, within these two general issues, treatment options were quite heterogeneous: seven subgroups were identified by whether cisplatin was present in either the treatment or the control arm. We conclude that the internal coherence and development of randomized clinical trials in advanced ovarian cancer and their methodologic soundness are quite poor. In this situation meta-analysis cannot go beyond a systematic attempt to answer a very general "treatment effectiveness" question

A multicentre, randomised, open-label, controlled trial evaluating equivalence of inhalational and intravenous anaesthesia during elective craniotomy.

Context A clear preference for intravenous or inhalational anaesthesia has not been established for craniotomy in patients without signs of cerebral hypertension. Objectives The NeuroMorfeo trial was designed to test equivalence of inhalational and intravenous anaesthesia maintenance techniques in the postoperative recovery of patients undergoing elective supratentorial surgery. Design This trial is a multicentre, randomised, open-label, equivalence design. A balanced stratified randomisation scheme was maintained using a centralised randomisation service. Equivalence was tested using the two one-sided tests procedure. Setting Fourteen Italian neuroanaesthesia centres participated in the study from December 2007 to March 2009. Patients Adults, 18 to 75 years old, scheduled for elective supratentorial intracranial surgery under general anaesthesia were eligible for enrolment if they had a normal preoperative level of consciousness and no clinical signs of intracranial hypertension. Interventions Patients were randomised to one of three anaesthesia maintenance protocols to determine if sevoflurane\u2013 remifentanil or sevoflurane\u2013fentanyl were equivalent to propofol\u2013remifentanil. Main outcome measures The primary outcome was the time to achieve an Aldrete postanaesthesia score of at least 9 after tracheal extubation. Secondary endpoints included haemodynamic parameters, quality of the surgical field, perioperative neuroendocrine stress responses and routine postoperative assessments. Results Four hundred and eleven patients [51% men, mean age 54.8 (SD 13.3) years] were enrolled. Primary outcome data were available for 380. Median (interquartiles) times to reach an Aldrete score of at least 9 were 3.48 (2.02 to 7.56), 3.25 (1.21 to 6.45) and 3.32 min (1.40 to 8.33) for sevoflurane\u2013fentanyl, sevoflurane\u2013remifentanil and propofol\u2013remifentanil anaesthesia respectively, which confirmed equivalence using the two one-sided tests approach. Between-treatment differences in haemodynamic variables were small and not clinically relevant. Urinary catecholamine and cortisol responses had significantly lower activation with propofol\u2013remifentanil. Postoperative pain and analgesic requirements were significantly higher in the remifentanil groups. Conclusion Equivalence was shown for inhalational and intravenous maintenance anaesthesia in times to reach an Aldrete score of at least 9 after tracheal extubation. Haemodynamic variables, the quality of surgical field and postoperative assessments were also similar. Perioperative endocrine stress responses were significantly blunted with propofol\u2013remifentanil and higher analgesic requirements were recorded in the remifentanil groups. Trial registration: Eudract2007\u2013005279-32