Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project.

BACKGROUND: Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking. OBJECTIVE: To assess the association between the Testosterone (T)-to-Estradiol (E2) Ratio (T/E2) and platelet activation biomarkers in IHD and its predictive value on adverse outcomes. METHODS: The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary angiography and/or percutaneous coronary interventions. Serum T/E2 ratios E2, levels of thromboxane B2 (TxB2) and nitrates (NO), were measured at admission and major adverse events, including all-cause mortality, were collected during a long-term follow-up. RESULTS: Among 509 adults with IHD (mean age 67 ± 11 years, 30% females), males were older with a more adverse cluster of cardiovascular risk factors than females. Acute coronary syndrome and non-obstructive coronary artery disease were more prevalent in females versus males. The lower sex-specific T/E2 ratios identified adults with the highest level of serum TxB2 and the lowest NO levels. During a median follow-up of 23.7 months, the lower sex-specific T/E2 was associated with higher all-cause mortality (HR 3.49; 95% CI 1.24-9.80; p = 0.018). In in vitro, platelets incubated with T/E2 ratios comparable to those measured in vivo in the lowest quartile showed increased platelet activation as indicated by higher levels of aggregation and TxB2 production. CONCLUSION: Among adults with IHD, higher T/E2 ratio was associated with a lower long-term risk of fatal events. The effect of sex hormones on the platelet thromboxane release may partially explain such finding.

The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive guidelines for the management of Atrial Fibrillation

The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then, periodic updates were published dealing with rapidly changing areas. However, since 2010 a large number of developments had accumulated in a wide range of areas, motivating the committee to complete a thorough guideline review. The 2020 iteration of the CCS AF guidelines represents a comprehensive renewal that integrates, updates, and replaces the past decade of guidelines, recommendations, and practical tips. It is intended to be used by practicing clinicians across all disciplines who care for patients with AF. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system was used to evaluate recommendation strength and the quality of evidence. Areas of focus include: AF classification and definitions, epidemiology, pathophysiology, clinical evaluation, screening and opportunistic AF detection, detection and management of modifiable risk factors, integrated approach to AF management, stroke prevention, arrhythmia management, sex differences, and AF in special populations. Extensive use is made of tables and figures to synthesize important material and present key concepts. This document should be an important aid for knowledge translation and a tool to help improve clinical management of this important and challenging arrhythmia.

Le programme de lignes directrices de la Société canadienne de cardiologie (SCC) en matière de fibrillation auriculaire (FA) a été élaboré pour aider les cliniciens à prendre en charge ces patients complexes, ainsi que pour orienter les décideurs politiques et les systèmes de soins de santé sur des questions connexes. La dernière édition complète des lignes directrices de la SCC en matière de FA a été publiée en 2010. Depuis lors, des mises à jour périodiques ont été publiées, traitant de domaines en évolution rapide. Cependant, en 2020, un grand nombre de développements s'y étaient ajoutés, couvrant un large éventail de domaines, ce qui a motivé le comité à créer une refonte complète des lignes directrices. L'édition 2020 des lignes directrices de la SCC en matière de FA représente un renouvellement complet qui intègre, met à jour et remplace les lignes directrices, les recommandations et les conseils pratiques des dix dernières années. Elle est destinée à être utilisée par les cliniciens praticiens de toutes les disciplines qui s'occupent de patients souffrant de FA. L'approche GRADE (Gradation des Recommandations, de l'Appréciation, du Développement et des Évaluations) a été utilisée pour évaluer la pertinence des recommandations et la qualité des résultats. Les domaines d'intérêt incluent : la classification et les définitions de la FA, son épidémiologie, sa physiopathologie, l'évaluation clinique, le dépistage de la FA, la détection et la gestion des facteurs de risque modifiables, l'approche intégrée de la gestion de la FA, la prévention des accidents vasculaires cérébraux, la gestion de l'arythmie, les différences entre les sexes et la FA dans des populations particulières. Des tableaux et figures ont été largement utilisés pour synthétiser les éléments importants et présenter les concepts clés. Ce document devrait représenter une aide importante pour l'intégration des connaissances et un outil pour aider à améliorer la gestion clinique de cette arythmie importante et difficile à traiter.

A Phase II trial of 8 weeks of degarelix for prostate volume reduction: Efficacy and hormonal recovery.

PURPOSE: The purpose of this study was to determine the efficacy of 8 weeks of degarelix for prostate downsizing before interstitial brachytherapy. We also report associated toxicity and the time course of endocrine recovery over the following 12 months. METHODS AND MATERIALS: Fifty patients were accrued to an open-label Phase II clinical trial (www.clinicaltrials.gov ID NCT01446991). Baseline prostate transrectal ultrasound (TRUS) was performed on all patients followed by degarelix administration and a repeat TRUS at Week 8. Brachytherapy was performed within 4 weeks of the 8-week TRUS for all patients who achieved suitable downsizing. RESULTS: The median prostate volume was reduced from 65.0 cc (interquartile range [IQR]: 55.2-80.0 cc) to 48.2 cc at 8 weeks (IQR: 41.2-59.3 cc), representing a median decrease of 26.2% (IQR: 21-31%). Functional recovery of testosterone within an age-adjusted normal range occurred at a median of 34.1 weeks (IQR: 28.2-44.5 weeks) from the date of the final injection. Despite this recovery, follicle-stimulating hormone and luteinizing hormone levels remained abnormally elevated throughout 12 months. Quality-of-life implications are discussed. CONCLUSIONS: Degarelix is effective for prostate downsizing before prostate brachytherapy with a median volume decrease of 26.2% by 8 weeks. Despite the short course of treatment and eventual testosterone recovery, follicle-stimulating hormone and luteinizing hormone remain elevated beyond 12 months. Further investigation with randomized comparisons to other hormonal agents is warranted.

Excess psychosocial burden in women with diabetes and premature acute coronary syndrome.

AIM: Diabetes is a stronger risk factor for acute coronary syndrome for women than men. We investigate whether behavioural and psychosocial factors contribute to the disparity in acute coronary syndrome risk and outcomes among women with diabetes relative to women without diabetes and men. METHODS: Among 939 participants in the GENESIS-PRAXY cohort study of premature acute coronary syndrome (age ≤ 55 years), we compared the prevalence of traditional and non-traditional factors by sex and Type 2 diabetes status. In a case-only analysis, we used generalized logit models to investigate the influence of traditional and non-traditional factors on the interaction of sex and diabetes. RESULTS: In 287 women (14.3% with diabetes) and 652 men (10.4% with diabetes), women and men with diabetes showed a heavier burden of traditional cardiac risk factors compared with individuals without diabetes. Women with diabetes were more likely to be the primary earner and have more anxiety relative to women without diabetes, and reported worse perceived health compared with women without diabetes and men with diabetes. The interaction term for sex and diabetes (odds ratio (OR) 1.40, 95% confidence intervals (95% CI) 0.83-2.36) was diminished after additional adjustment for non-traditional factors (OR 1.12, 95% CI 0.54-2.32), but not traditional factors alone (OR 1.41, 95% CI 0.84-2.36). CONCLUSIONS: We observed trends toward a more adverse psychosocial profile among women with diabetes and incident acute coronary syndrome compared with women without diabetes and men with diabetes, which may explain the increased risk of acute coronary syndrome in women with diabetes and may also contribute to worse outcomes.

2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update

Omega-3 fatty acids and the genetic risk of early onset acute coronary syndrome.

BACKGROUND AND AIMS: Recent gene-environment interaction studies suggest that diet may influence an individual's genetic predisposition to cardiovascular risk. We evaluated whether omega-3 fatty acid intake may influence the risk for acute coronary syndrome (ACS) conferred by genetic polymorphisms among patients with early onset ACS. METHODS AND RESULTS: Our population consisted of 705 patients of white European descent enrolled in GENESIS-PRAXY, a multicenter cohort study of patients aged 18-55 years and hospitalized with ACS. We used a case-only design to investigate interactions between the omega-3 index (a validated biomarker of omega-3 fatty acid intake) and 30 single nucleotide polymorphisms (SNPs) robustly associated with ACS. We used logistic regression to assess the interaction between each SNP and the omega-3 index. Interaction was also assessed between the omega-3 index and a genetic risk score generated from the 30 SNPs. All models were adjusted for age and sex. An interaction for increased ACS risk was found between carriers of the chromosome 9p21 variant rs4977574 and low omega-3 index (OR 1.57, 95% CI 1.07-2.32, p = 0.02), but this was not significant after correction for multiple testing. Similar results were obtained in the adjusted model (OR 1.55, 95% CI 1.05-2.29, p = 0.03). We did not observe any interaction between the genetic risk score or any of the other SNPs and the omega-3 index. CONCLUSION: Our results suggest that omega-3 fatty acid intake may modify the genetic risk conferred by chromosome 9p21 variation in the development of early onset ACS and requires independent replication.

Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: individual patient data meta-analysis.

BACKGROUND: The association between depression after myocardial infarction and increased risk of mortality and cardiac morbidity may be due to cardiac disease severity. AIMS: To combine original data from studies on the association between post-infarction depression and prognosis into one database, and to investigate to what extent such depression predicts prognosis independently of disease severity. METHOD: An individual patient data meta-analysis of studies was conducted using multilevel, multivariable Cox regression analyses. RESULTS: Sixteen studies participated, creating a database of 10 175 post-infarction cases. Hazard ratios for post-infarction depression were 1.32 (95% CI 1.26-1.38, P<0.001) for all-cause mortality and 1.19 (95% CI 1.14-1.24, P<0.001) for cardiovascular events. Hazard ratios adjusted for disease severity were attenuated by 28% and 25% respectively. CONCLUSIONS: The association between depression following myocardial infarction and prognosis is attenuated after adjustment for cardiac disease severity. Still, depression remains independently associated with prognosis, with a 22% increased risk of all-cause mortality and a 13% increased risk of cardiovascular events per standard deviation in depression z-score.

Obesity and C-reactive protein in various populations: a systematic review and meta-analysis.

Obesity has been associated with elevated levels of C-reactive protein (CRP), a marker of inflammation and predictor of cardiovascular risk. The objective of this systematic review and meta-analysis was to estimate the associations between obesity and CRP according to sex, ethnicity and age. MEDLINE and EMBASE databases were searched through October 2011. Data from 51 cross-sectional studies that used body mass index (BMI), waist circumference (WC) or waist-to-hip ratio (WHR) as measure of obesity were independently extracted by two reviewers and aggregated using random-effects models. The Pearson correlation (r) for BMI and ln(CRP) was 0.36 (95% confidence interval [CI], 0.30-0.42) in adults and 0.37 (CI, 0.31-0.43) in children. In adults, r for BMI and ln(CRP) was greater in women than men by 0.24 (CI, 0.09-0.37), and greater in North Americans/Europeans than Asians by 0.15 (CI, 0-0.28), on average. In North American/European children, the sex difference in r for BMI and ln(CRP) was 0.01 (CI, -0.08 to 0.06). Although limited to anthropometric measures, we found similar results when WC and WHR were used in the analyses. Obesity is associated with elevated levels of CRP and the association is stronger in women and North Americans/Europeans. The sex difference only emerges in adulthood.

Sex differences in young patients with acute myocardial infarction.

AIMS: To identify sex differences in risk factors, presenting symptoms and outcomes of young patients with acute myocardial infarction. METHODS: We adopted a comprehensive approach and performed two parallel studies: (1) using provincial administrative databases from Quebec, Canada from 2000 to 2007, we identified baseline characteristics and post-acute myocardial infarction survival of patients aged < 50 years (n = 10,619); (2) to overcome the lack of clinical data in the administrative databases, a medical chart review was performed on 215 patients < 50 years of age with an acute myocardial infarction between April 2000 and August 2006 from our institution. RESULTS: Administrative cohort: fewer women than men sought medical attention for retrosternal chest pain 1-month pre-acute myocardial infarction (P = 0.035). Diabetes and hypertension were more prevalent in women, and patients equally received interventional procedures post-infarction. Diabetes significantly reduced post-infarction survival in men and women [HR = 2.02 (95% CI 1.21-3.36) and HR = 2.25 (95% CI 1.06-4.80), respectively]. However, young women had greater post-infarction mortality in-hospital and up to 1 year after discharge (4.23% vs. 2.21%, respectively; P = 0.005). Medical chart review: diabetes and hypertension were more prevalent in women, while men were more obese. There were no significant sex differences in typical presenting symptoms, or in interventional procedures post-infarction. CONCLUSIONS: Young men and women with acute myocardial infarctions equally presented with retrosternal chest pain, although fewer women sought medical attention for retrosternal chest pain before admission. Diabetes and hypertension were more prevalent in young women, and mortality was higher in young female patients. Our results highlight the continued need for diabetes prevention and control in young patients, especially women.

The effect of smoking cessation counselling in pregnant women: a meta-analysis of randomised controlled trials.

BACKGROUND: Pregnant smokers are often prescribed counselling as part of multicomponent cessation interventions. However, the isolated effect of counselling in this population remains unclear, and individual randomised controlled trials (RCTs) are inconclusive. OBJECTIVE: To conduct a meta-analysis of RCTs examining counselling in pregnant smokers. SEARCH STRATEGY: We searched the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline and PsycINFO databases for RCTs evaluating smoking cessation counselling. SELECTION CRITERIA: We included RCTs conducted in pregnant women in which the effect of counselling could be isolated and those that reported biochemically validated abstinence at 6 or 12 months after the target quit date. DATA COLLECTION AND ANALYSIS: Overall estimates were derived using random effects meta-analysis models. MAIN RESULTS: Our search identified eight RCTs (n = 3290 women), all of which examined abstinence at 6 months. The proportion of women that remained abstinent at the end of follow up was modest, ranging from 4 to 24% among those randomised to counselling and from 2 to 21% among control women. The absolute difference in abstinence reached a maximum of only 4%. Summary estimates are inconclusive because of wide confidence intervals, albeit with little evidence to suggest that counselling is efficacious at promoting abstinence (odds ratio 1.08, 95% confidence interval 0.84-1.40). There was no evidence to suggest that efficacy differed by counselling type. CONCLUSIONS: Available data from RCTs examining the isolated effect of smoking cessation counselling in pregnant women are limited but sufficient to rule out large treatment effects. Future RCTs should examine pharmacological therapies in this population.

Reporting on sex-based analysis in clinical trials of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker efficacy.

BACKGROUND: Clinical practice recommendations for hypertension do not make recommendations specific to men or women. However, the sex hormones appear to modulate differently the renin-angiotensin system (RAS), which plays a central role in the regulation of blood pressure. Today, little is known about the effects of sex on the efficacy of therapies that antagonize the RAS, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). OBJECTIVE: To identify randomized controlled trials evaluating the efficacy of ACEIs and ARBs in preventing major cardiovascular outcomes, determine what proportion of the trial participants were female, and evaluate whether there was any evidence of a sex difference in the efficacy of these agents. METHODS: A systematic review of the literature was conducted to identify randomized controlled trials that used either ACEIs or ARBs for the treatment of hypertension. RESULTS: Thirteen ACEI trials and nine ARB trials were identified. Sex-specific outcome data were available in six of the ACEI trials and three of the ARB trials. These trials enrolled 74,105 patients; 39.1% were women. Seven of the nine trials indicated that ACEIs or ARBs may be slightly more beneficial in men. The magnitude of these differences, in most trials, was small. CONCLUSIONS: Sex-specific data are reported in 43% of large hypertension clinical trials. Review of the trials reporting sex-specific effect sizes indicates that ACEIs and ARBs may be more effective in men.

Effectiveness of antiresorptive agents in the prevention of recurrent hip fractures.

UNLABELLED: Hip fracture is associated with recurrent fractures and increased mortality. The results of our retrospective cohort study support the use of antiresorptive agents to prevent recurrent hip fractures in this population. INTRODUCTION: Hip fracture, the most serious consequence of osteoporosis, is associated with recurrent fractures and increased mortality. Antiresorptive therapy has proven efficacy in the prevention of fractures after vertebral fractures. It is unknown if it can prevent recurrent fractures after a hip fracture. METHODS: We designed a population based, retrospective cohort study, using administrative databases and identified patients hospitalized for a hip fracture between 1996 and 2002. The exposure was defined as being dispensed a prescription for an antiresorptive agent at any time following discharge. Multivariate Cox regression models were used to estimate the hazard ratio of recurrent hip fracture. Subgroup and propensity score analyses were performed. RESULTS: A total of 20,644 patients were identified; 6,779 filled a prescription for antiresorptive agents. There were 992 recurrent hip fractures. Patients exposed to antiresorptives had a 26% reduction in the rate of recurrent fractures (adjusted hazard ratio 0.74; 95% CI, 0.64-0.86) compared to patients who were not. All subgroups experienced a reduction in recurrent fracture, except the very elderly. Propensity score analyses were consistent with the main analysis. CONCLUSIONS: Antiresorptive therapy reduces the risk of recurrent hip fractures in elderly patients. These results provide evidence that this therapy should be considered for secondary prevention of hip fractures.

Impact of diabetes on 12-month outcomes following coronary artery bypass graft surgery: results from the ROSETTA-CABG Registry.

BACKGROUND: Diabetes mellitus is associated with poorer long-term outcomes following coronary artery bypass graft (CABG) surgery. However, little is known about the impact of diabetes mellitus on outcomes during the first 12 months following CABG. OBJECTIVES: To examine the relationship between diabetes mellitus and outcomes during the 12 months following CABG. METHODS: The Routine versus Selective Exercise Treadmill Testing after Coronary Artery Bypass Grafting (ROSETTA-CABG) Registry is a prospective, multicentre study examining the use of functional testing after CABG surgery. A total of 398 patients who were enrolled in the ROSETTA-CABG Registry were examined. Diabetic status was defined by medication use at discharge. Only patients undergoing a first successful CABG (all ischemic areas thought to be revascularized) were included. RESULTS: Among the 398 patients, 37 (9.3%) were receiving insulin, 67 (16.8%) were receiving oral hypoglycemic agents, and 294 (73.9%) were not receiving insulin or oral hypoglycemic agents. Insulin-treated patients had a higher 12-month incidence of composite clinical events consisting of readmission for unstable angina, myocardial infarction or death than did oral hypoglycemic-treated patients and nondiabetic patients (21.6% versus 4.5% and 6.0%, respectively; P=0.0003). Insulin-treated patients were also more likely to undergo repeat cardiac catheterization than were oral hypoglycemic-treated patients and nondiabetic patients (18.9% versus 8.8% and 7.9%, respectively; P=0.03). After controlling for other variables, use of insulin was independently associated with a composite of adverse clinical events (OR 3.80, 95% CI 1.5 to 9.6, P=0.005). CONCLUSIONS: During the 12-month period after a successful CABG, insulin-treated patients had a higher rate of adverse cardiac events than did patients receiving oral hypoglycemic agents and nondiabetic patients. These results suggest that diabetic patients may benefit from more aggressive surveillance during the first year after CABG surgery.

In vitro characterization of a purified NS2/3 protease variant of hepatitis C virus.

The cleavage of the hepatitis C virus polyprotein between the nonstructural proteins NS2 and NS3 is mediated by the NS2/3 protease, whereas the NS3 protease is responsible for the cleavage of the downstream proteins. Purification and in vitro characterization of the NS2/3 protease has been hampered by its hydrophobic nature. NS2/3 protease activity could only be detected in cells or in in vitro translation assays with the addition of microsomal membranes or detergent. To facilitate purification of this poorly characterized protease, we truncated the N-terminal hydrophobic domain, resulting in an active enzyme with improved biophysical properties. We define a minimal catalytic region of NS2/3 protease retaining autocleavage activity that spans residues 904-1206 and includes the C-terminal half of NS2 and the N-terminal NS3 protease domain. The NS2/3 (904-1206) variant was purified from Escherichia coli inclusion bodies and refolded by gel filtration chromatography. The purified inactive form of NS2/3 (904-1206) was activated by the addition of glycerol and detergent to induce autocleavage at the predicted site between Leu(1026) and Ala(1027). NS2/3 (904-1206) activity was dependent on zinc ions and could be inhibited by NS4A peptides, peptides that span the cleavage site, or an N-terminal peptidic cleavage product. This NS2/3 variant will facilitate the development of an assay suitable for identifying inhibitors of HCV replication.

Predictors of quality of life 6 months and 1 year after acute myocardial infarction.

BACKGROUND: Quality of life (QOL) is an increasingly important outcome measure after hospital admission for acute myocardial infarction (AMI). However, the ability to adjust these outcomes for differences between compared groups of patients is limited because the predictors of QOL after AMI are unknown. METHODS: To identify any clinical, demographic, and psychosocial characteristics of patients at admission that were independent predictors of QOL 6 months and 1 year after AMI, we measured physical and mental QOL (Short Form-36 Physical and Mental Component summary scores) and overall QOL (EuroQol health perception scale) in a prospective cohort of 587 patients admitted at 10 hospitals in Quebec. A set of plausible multivariate linear regression models was created for each outcome measure with use of the Bayesian Information Criterion. RESULTS: Mean physical, mental, and overall QOL scores corresponding to the time immediately before admission (baseline) were 45 (95% confidence interval [CI] 44-46), 47 (95% CI 46-48), and 70 (95% CI 68-72), respectively. By 1 year, mean physical, mental, and overall QOL scores were close to baseline (45 [95% CI 44-46], 48 [95% CI 47-49], and 73 [95% CI 71-74], respectively). The predictors of physical, mental, and overall QOL were similar at 6 months and 1 year. Important predictors of physical QOL were the corresponding score at baseline, age, and previous bypass surgery (beta coefficients at 1 year: 5 [per 10-point difference in baseline score], -1 [per 10-year age difference], 5.3; 95% CIs 4 to 5, -2 to -1, -9.2 to -1.3, respectively). Predictors of mental QOL were the corresponding score at baseline and depression (beta coefficients at 1 year: 3 [per 10-point difference in baseline score], -3 [per 10-point difference in depression score]; 95% CIs 2 to 4, -5 to -2, respectively). Predictors of overall QOL included the corresponding score at baseline and age (beta at 1 year: 2 [per 10-point score difference], -3 [per 10-year age difference]; 95% CIs 1 to 3, -4 to -1, respectively). Depression was also a predictor of impaired physical and overall QOL at 6 months (beta at 6 months: -1.6 [per 10-point score difference], -5.4 [per 10-point score difference]; 95% CIs -2.9 to -0.4, -7.7 to -3.2, respectively). No variables related to treatments received in-hospital were found in the most clinically relevant models. CONCLUSIONS: These results suggest that age and psychosocial characteristics at baseline are the most important predictors of QOL after AMI. Other clinical characteristics and treatments received in-hospital do not appear to strongly affect patients' long-term perceptions of QOL.

Use of routine functional testing after percutaneous transluminal coronary angioplasty: results from the ROSETTA Registry.

BACKGROUND: The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for exercise testing suggest that only selected groups of high-risk patients should undergo routine functional testing after percutaneous transluminal coronary angioplasty (PTCA) for the detection of restenosis. OBJECTIVES: Our purpose was (1) to document the patterns of use of post-PTCA functional testing and (2) to determine whether the choice of functional testing strategy is related to clinical characteristics of patients or whether physicians use a similar strategy for all their patients. METHODS: The Routine Versus Selective Exercise Treadmill Testing After Angioplasty (ROSETTA) Registry is a prospective study examining the use of functional testing among 788 patients at 13 centers in 5 countries. RESULTS: During the 6-month period after a successful PTCA, 49% of patients underwent functional testing (range among centers 10%-81%). Among patients who underwent functional testing, 39% had a clinical indication and 61% had functional testing as a routine follow-up. The first functional test was performed a median of 7 weeks after PTCA, with 13% of patients having second tests at a median of 14 weeks and 4% having additional tests at a median of 20 weeks. Univariate and multivariate analyses demonstrated that the chief determinant of the use of routine functional testing was clinical center. Aside from age (P <.0001), no baseline clinical or procedural characteristics were consistently associated with the use of routine functional testing after PTCA. CONCLUSIONS: Physicians do not appear to be adhering to the ACC/AHA guidelines for exercise testing regarding the routine use of post-PTCA functional testing. None of the clinical characteristics identified by the ACC/AHA guidelines were associated with the routine use of post-PTCA functional testing, and the primary determinant of functional testing was the location of the center at which the patient had the PTCA.

Recurrent ischemia after thrombolysis for acute myocardial infarction.

BACKGROUND: Reliable predictors have yet to be found for recurrent ischemia after thrombolysis for acute myocardial infarction (AMI), nor do we know whether early angiography can herald recurrent ischemia. This study sought to investigate the relationship between recurrent ischemia and cardiac procedures after thrombolysis for AMI. METHODS: The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial prospectively studied recurrent ischemia, which was defined as the presence of angina and changes in hemodynamics or the electrocardiogram. Cox regression analysis was used to identify predictors of recurrent ischemia. Other variables examined included time to coronary angiography and revascularization. RESULTS: Of 21,772 US GUSTO-I patients, 6313 (29%) had recurrent ischemia before discharge. Women (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.17-1.33) and patients with hypercholesterolemia (HR 1.14, 95% CI 1.07-1.22) or prior angina (HR 1.40, 95% CI 1.32-1.49) had a higher likelihood of recurrent ischemia. Current smoking and hours to thrombolysis were inversely related to recurrent ischemia (HR 0.86, 95% CI 0.81-0.92, HR 0.97, 95% CI 0.95- 0.99, respectively). Patients who underwent angiography before recurrent ischemia had a marginally increased risk of ischemia within 12 hours after angiography (HR 1.2, 95% CI 1.1-1.4); ultimately, they had a considerably lower risk 1 week after angiography than did patients without angiography (HR 0.57, 95% CI 0.45-0.72). CONCLUSIONS: Female sex, hypercholesterolemia, prior angina, and nonsmoking status weakly predict recurrent ischemia. Early coronary angiography reduces recurrent ischemia, probably because high-risk patients are identified and revascularized.

Discharge prescriptions following admission for acute myocardial infarction at tertiary care and community hospitals in Quebec.

BACKGROUND: Many physicians are not adhering to the recommendations found in evidence-based guidelines for the treatment of acute myocardial infarction (AMI). Physicians who practise in tertiary care settings may show better adherence to guideline recommendations than physicians who practise in other settings. OBJECTIVE: To determine whether there is an association between the practice setting of admission for AMI and discharge prescriptions for cardiac drugs recommended in evidence-based guidelines. PATIENTS AND METHODS: Discharge prescription data from a prospective cohort of patients with AMI admitted at five tertiary care (n=250) and five community hospitals (n=331) in Quebec from December 1996 to November 1998 were examined. RESULTS: The proportions of patients who were prescribed recommended drugs at tertiary care hospitals compared with those at community hospitals were as follows: beta-blockers (78% versus 74%, respectively; 95% CI around the difference - 4% to 11%), lipid-lowering drugs (45% versus 39%, respectively; 95% CI - 2% to 15%) and angiotensin-converting enzyme (ACE) inhibitors (44% versus 57%, respectively; 95% CI - 22% to - 5%). In adjusted analyses, practice setting was not associated with the prescription of beta-blockers (odds ratio [OR] for tertiary care 1.36; 95% CI 0.82 to 2.24) or lipid-lowering drugs (OR for tertiary care 1.06; 95% CI 0.67 to 1.68). However, tertiary care admission reduced the likelihood of ACE inhibitor prescription (OR 0.50; 95% CI 0.32 to 0.77). This association may have been due to the increased likelihood of ACE inhibitor prescription for patients with hypertension at community hospitals (OR 2.13; 95% CI 1.23 to 3.67). The results also showed that older patients were less likely to be prescribed beta-blockers or lipid-lowering drugs, women were less likely to be prescribed beta-blockers and patients with diabetes mellitus were less likely to be prescribed lipid-lowering drugs (OR 0.45; 95% CI 0.23 to 0.89). CONCLUSION: No strong association was found between the practice setting of admission for AMI and discharge prescriptions for cardiac drugs recommended in evidence-based guidelines. Prescription rates for recommended drugs were high, yet results suggest that there is room for improvement with regard to patients with diabetes, women and older patients.

Iron stores and coronary artery disease: a clinical application of a method to incorporate measurement error of the exposure in a logistic regression model.

Rates of coronary artery disease (CAD) increase sharply after menopause. We examined the hypotheses that high iron stores, as measured by plasma ferritin levels, are a risk factor for CAD and that the increase in iron stores after menopause is at least in part responsible for the rise in CAD in women. We also investigated measurement error of plasma ferritin using a Bayesian conditional independence model and incorporated it into the estimation of the odds ratio (OR) for males. Cases had >/=1 coronary artery stenosis >/=70%. Controls had no visible coronary lesions on angiography. The median plasma ferritin level was 48 mg/L (interquartile range: 28 to 86) among 244 cases and 45 mg/l (24 to 85) among 140 controls. The multivariate analyses among females, males, and females and males combined did not support an association between plasma ferritin levels and CAD (OR for one unit change in log ferritin 1.01, 95% CI 0.71-1.44, OR 0.95, 95% CI 0.66-1.37 and OR 0.95, 95% CI 0.75-1.21, respectively). Accounting for the measurement error of ferritin in males slightly improved the precision of the estimate of the OR but did not unmask an association (OR: 0.94, 95% CI 0.69-1.30). We conclude that high ferritin levels before or after menopause are not associated with CAD. Measurement error might be considered in situations where a one-time measurement is assumed to be representative of long-term exposure.

Changes in the treatment and outcomes of acute myocardial infarction in Quebec, 1988-1995.

BACKGROUND: Few studies have reported population-based information on the treatment trends and outcomes of patients who have had an acute myocardial infarction (AMI). We therefore examined patterns of care and outcomes for AMI patients in Quebec, Canada, between 1988 and 1995. METHODS: Longitudinal data files of hospital admissions in Quebec (Med-Echo database) and inpatient and outpatient services (Régie de l'Assurance Maladie du Québec database) were used to construct cohorts of all AMI patients in the province between 1988 and 1995. Temporal trends in the use of cardiac procedures after an AMI, discharge prescriptions and mortality rates were examined. RESULTS: Between 1988 and 1995 the age- and sex-adjusted rates of AMI in the Quebec population declined (148 per 100,000 in 1988 to 137 per 100,000 in 1995). The use of intensive cardiac procedures increased in the same period; the 1-year cumulative incidence rate of catheterization increased from 28% in 1988 to 31% in 1994, that of angioplasty rose from 8% to 15% and that of coronary artery bypass surgery from 6% to 8%. Prescriptions for ASA, beta-blockers, lipid-lowering agents and angiotensin-converting enzyme inhibitors increased, and prescriptions for nitrates and calcium antagonists decreased. These temporal changes were paralleled by a decrease in mortality rates post-AMI. All-cause 1-year cumulative incidence mortality rates decreased from 23% in 1988 to 19% in 1994. INTERPRETATION: The decrease in AMI-related mortality in Quebec between 1988 and 1995 may be linked to changes in treatment strategies (i.e., increased use of cardiac surgical procedures and medications shown to increase survival).