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Globally, vascular diseases are a leading cause of morbidity and mortality. Many of the most significant risk factors for vascular disease have a gendered dimension, and sex differences in vascular diseases incidence are apparent, worldwide. In this narrative review, we provide a contemporary picture of sex- and gender-related determinants of vascular disease. We illustrate key factors underlying sex-specific risk stratification, consider similarities and sex differences in vascular disease risk and outcomes with comparisons of data from the global North (ie, developed high-income countries in the Northern hemisphere and Australia) and the global South (ie, regions outside Europe and North America), and explore the relationship between country-level gendered inequities in vascular disease risk and the United Nation's gender inequality index. Review findings suggest that the rising incidence of vascular disease in women is partly explained by an increase in the prevalence of traditional risk factors linked to gender-related determinants such as shifting roles and relations related to the double burden of employment and caregiving responsibilities, lower educational attainment, lower socioeconomic status, and higher psychosocial stress. Social isolation partly explained the higher incidence of vascular disease in men. These patterns were apparent across the global North and South. Study findings emphasize the necessity of taking into account sex differences and gender-related factors in the determination of the vascular disease risk profiles and management strategies. As we move toward the era of precision medicine, future research is needed that identifies, validates, and measures gender-related determinants and risk factors in the global South.

Background An effective and safe oral anticoagulation (OAC) strategy for patients with new postoperative AF (POAF) after noncardiac surgery remains unclear. We aimed to determine the association between OAC use and 1) thromboembolic events and 2) major bleeding in patients with POAF after noncardiac surgery. Methods A retrospective cohort (1999-2015) was used to identify patients with new POAF after inpatient noncardiac surgery. Initiation of OAC was defined as prescription of an OAC within 30 days following hospital discharge. Times to first hospital admission or emergency department visit for a thromboembolic or major bleeding event were compared using Cox proportional hazards models. Results We identified 22,007 patients with new POAF after inpatient noncardiac surgery. The majority of patients had intermediate (CHA2DS2-VASc 2-3: 45%) to high (CHA2DS2-VASc ≥ 4: 42%) thromboembolic risk. During a mean follow-up of 4 years, a total of 1099 (5%) thromboembolic and 3250 (15%) bleeding events occurred. Compared with patients not on anticoagulation, anticoagulation did not reduce the risk for thromboembolic events (adjusted hazard ratio [aHR] 0.89, 95% CI 0.73-1.07). In patients initiated on anticoagulation, there was an association with a higher risk for major bleeding (aHR 1.14, 95% CI 1.04-1.25). Conclusions In patients with new POAF after noncardiac surgery, anticoagulation was not associated with a reduction in long-term thromboembolic events; however, this was accompanied by an overall increased risk for major bleeding. Future prospective clinical studies are needed to better address the role for anticoagulation therapy in the setting of POAF after noncardiac surgery to understand the efficacy and safety of treatment.

Background Peripartum cardiomyopathy (PPCM) and preeclampsia are strongly associated, yet a description of risk factors for PPCM among women with preeclampsia is currently lacking. Additionally, the effect of preeclampsia on PPCM-related outcomes is not well known. Methods We constructed a cohort of delivery admissions from 2011 to 2014 using a large US administrative database (Marketscan). We assessed risk factors for the development of PPCM among women with preeclampsia. We compared the risks of major adverse cardiovascular events (MACE) at 6 months between PPCM with co-incident preeclampsia (pePPCM) and PPCM without preeclampsia (npePPCM). Results We included 1,024,035 pregnancies, of which 64,503 (6.3%) had preeclampsia. A total of 874 had PPCM (283 with preeclampsia and 591 without preeclampsia). Among women with preeclampsia, clinical risk factors for PPCM consisted in chronic kidney disease (OR 3.18, 95% CI [1.51, 6.69]), multiple pregnancy (OR 2.11, 95% CI [1.49, 2.98]), chronic hypertension (OR 1.88, 95% CI [1.43, 2.47]), advanced maternal age (OR 1.82, 95% CI [1.42, 2.33]), and type 2 diabetes (OR 1.58, 95% CI [1.00, 2.48]). Women with pePPCM had a higher risk of MACE than women with npePPCM (adjusted RR 1.29, 95% CI [1.06, 1.57]) due to increased rates of clinical heart failure and pulmonary embolism in the pePPCM group. Mortality did not differ between groups. Conclusion Preeclamptic women with risk factors for PPCM and women with pePPCM at increased risk of MACE should be followed closely. Further studies are required to determine whether preeclampsia affects the long-term prognosis of women with PPCM.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in atrial fibrillation (AF) management. This 2018 Focused Update addresses: (1) anticoagulation in the context of cardioversion of AF; (2) the management of antithrombotic therapy for patients with AF in the context of coronary artery disease; (3) investigation and management of subclinical AF; (4) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (5) acute pharmacological cardioversion of AF; (6) catheter ablation for AF, including patients with concomitant AF and heart failure; and (7) an integrated approach to the patient with AF and modifiable cardiovascular risk factors. The recommendations were developed 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 as Supplementary Material and are available on the CCS Web site. 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 2018 Focused Update, which is provided in the Supplementary Material.

BACKGROUND The impact of biological sex and social determinants of health (gender) on the prevalence of cardiovascular (CV) risk factors such as diabetes mellitus (DM) may vary by culture and health systems. In this study, we aimed to elucidate how sex and gender influence access to care and CV outcomes of individuals with DM across different countries. METHODS AND RESULTS Data from the Canadian Community Health Survey (2015-16) (N=109,659, 53.7% Females, 8.4% DM) and the European Health Interview Survey (N=316,333, 51.3% Females, 7.3% DM), were analyzed. A composite measure of socio-cultural gender was constructed (score range: 0-1; higher score identifying characteristics traditionally ascribed to women). The relationship between the gender score, antihyperglycemic care, complications and hospitalization of individuals with DM was assessed with a logistic regression model. European countries were stratified based on their Gender Inequality Index (GII); which quantifies gender disparity and inequity amongst various countries in the world, from low-GII (GII =0.1635). Characteristics traditionally ascribe to women (i.e., higher gender score) included greater stress level, being widowed or divorced, larger household size, higher education, good sense of belonging to community, and lower income in Canadians; while being divorced or widowed, having greater household size, lower education and lower income were found in Europeans. Sex and gender significantly influenced the standard care of patients with diabetes including periodic glucose and HbA1C monitoring. Canadian diabetic females were more likely to check their HbA1c (OR: 1.29, 95%CI:1.03-1.6), while European counterparts were less likely to check their blood sugar (OR: 0.89, 95%CI:0.79-0.99). A higher gender score in both populations was associated with less frequent monitoring of HbA1C and blood glucose levels (Table 1). When stratifying by GII, DM patients in countries with medium and high GII were less likely to check their blood glucose levels compared to low GII countries (Table1). Additionally, higher gender scores independent of sex were associated with higher risk of heart disease, stroke and hospitalization in all countries albeit European countries with medium to high GII, conferred a higher risk of all complications and hospitalization rates (Table1). CONCLUSION Regardless of biological sex, diabetic individuals with characteristics typically ascribed to women and those living in countries with greater gender inequality, exhibited poorer antihyperglycemic care, greater risk of cardiovascular complications, and higher hospitalization rates. Country-specific gender related factors and gender disparity must be targeted for improving health status and access to care of patients with DM.

Context Treatment guidelines recommend the use of combination therapies for smoking cessation, particularly behavioral therapy (BT) as an adjunct to pharmacotherapy. However, these guidelines rely on previous reviews with important limitations. This study's objective was to evaluate the efficacy of combination therapies compared with monotherapies, using the most rigorous data available. Evidence acquisition A systematic review and meta-analysis of RCTs of pharmacotherapies, BTs, or both were conducted. The Cochrane Library, Embase, PsycINFO, and PubMed databases were systematically searched from inception to July 2015. Inclusion was restricted to RCTs reporting biochemically validated abstinence at 12 months. Direct and indirect comparisons were made in 2015 between therapies using hierarchical Bayesian models. Evidence synthesis The search identified 123 RCTs meeting inclusion criteria (60,774 participants), and data from 115 (57,851 participants) were meta-analyzed. Varenicline with BT increased abstinence more than other combinations of a pharmacotherapy with BT (varenicline versus bupropion: OR=1.56, 95% credible interval [CrI]=1.07, 2.34; varenicline versus nicotine patch: OR=1.65, 95% CrI=1.10, 2.51; varenicline versus short-acting nicotine-replacement therapies: OR=1.68, 95% CrI=1.15, 2.53). Adding BT to any pharmacotherapy compared with pharmacotherapy alone was inconclusive, owing to wide CrIs (OR=1.17, CrI=0.60, 2.12). Nicotine patch with short-acting nicotine-replacement therapy appears safe and increases abstinence versus nicotine-replacement monotherapy (OR=1.63, CrI=1.06, 3.03). Data are limited concerning other pharmacotherapy combinations and their safety and tolerability. Conclusions Evidence suggests that combination therapy benefits may be less than previously thought. Combined with BT, varenicline increases abstinence more than other pharmacotherapy with BT combinations.

Background Following an episode of hypertensive disorder of pregnancy (HDP) women have an increased risk of cardiovascular disease over their lifetime. At the time of acute coronary syndrome we compared clinical information between women with and without a history of hypertension in pregnancy to gain further insight into the pathophysiology of cardiovascular disease in this population. Methods GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond—PRemature Acute Coronary SYdrome) is a prospective multicenter study, with recruitment between January 2009 and April 2013, including 242 parous women with premature acute coronary syndrome. Results The median age was 50years (IQR 6) and HDP was common; 43 (17.8%) women had prior gestational hypertension, 33 (13.6%) preeclampsia and 166 (68.6%) a prior normotensive pregnancy. Women with a history of HDP commonly had chronic hypertension and diabetes and those presenting with ST-elevation myocardial infarction were more likely to have a history of preeclampsia (aOR 3.12, 95% CI 1.22–8.01) than were women with prior normotensive pregnancies. Neither gestational hypertension (aOR 1.40, 95% CI 0.60–3.26) nor preeclampsia (aOR 0.63, 95% CI 0.23–1.74) was associated with a higher composite risk of three-vessel, left main or proximal left anterior descending coronary disease. Conclusion In this study of women with premature cardiovascular disease, ST-elevation myocardial infarction was associated with a history of preeclampsia possibly because of persistent endothelial dysfunction. High-risk coronary lesions on angiography did not appear to have an association with preeclampsia or gestational hypertension despite a high burden of traditional risk factors.

Background “Gender” reflects social norms for women and men, whereas “sex” defines biological characteristics. Gender-related characteristics explain some differences in access to care for premature acute coronary syndrome (ACS); whether they are associated with cardiovascular outcomes is unknown. Objectives This study estimated associations between gender and sex with recurrent ACS and major adverse cardiac events (MACE) (e.g., ACS, cardiac mortality, revascularization) over 12 months in patients with ACS. Methods We studied 273 women and 636 men age 18 to 55 years from GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome), a prospective observational cohort study, who were hospitalized for ACS between January 2009 and April 2013. Gender-related characteristics (e.g., social roles) were assessed using a self-administered questionnaire, and a composite measure of gender was derived. Outcomes included recurrent ACS and MACE over 12 months. Results Feminine roles and personality traits were associated with higher rates of recurrent ACS and MACE compared with masculine characteristics. This difference persisted for recurrent ACS, after multivariable adjustment (hazard ratio from score 0 to 100: 4.50; 95% confidence interval: 1.05 to 19.27), and was a nonstatistically significant trend for MACE (hazard ratio: 1.54; 95% confidence interval: 0.90 to 2.66). A possible explanation is increased anxiety, the only condition that was more prevalent in patients with feminine characteristics and that rendered the association between gender and recurrent ACS nonstatistically significant (hazard ratio: 3.56; 95% confidence interval: 0.81 to 15.61). Female sex was not associated with outcomes post-ACS. Conclusions Younger adults with ACS with feminine gender are at an increased risk of recurrent ACS over 12 months, independent of female sex.

We read with great interest the paper by Merrill et al. [(1)][1] reporting that spironolactone is associated with a reduction in all-cause mortality in women but not in men with heart failure with preserved ejection fraction, enrolled in the TOPCAT (Aldosterone Antagonist Therapy for Adults With

Previous studies on digoxin use in patients with atrial fibrillation (AF) and the risk of all-cause mortality found conflicting results. We conducted a population-based, retrospective, cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF, in Quebec province, Canada, from 1998 to 2012. The AF cohort was grouped into patients with and without heart failure (HF) and into digoxin and no-digoxin users according to the first prescription filled for digoxin within 30 days after AF hospital discharge. We derived propensity score-matched digoxin and no-digoxin treatment groups for the groups of patients with and without HF, respectively, and conducted multivariable Cox proportional hazards regression analyses to determine association between digoxin use and all-cause mortality. The AF propensity score-matched cohorts of patients with and without HF were well balanced on baseline characteristics. In the propensity score-matched HF group, digoxin use was associated with a 14% greater risk of all-cause mortality (adjusted hazard ratio 1.14, 95% confidence interval 1.10 to 1.17). In the propensity score-matched no-HF group, digoxin use was associated with a 17% greater risk of all-cause mortality (adjusted hazard ratio 1.17, 95% confidence interval 1.14 to 1.19). In conclusion, our retrospective analyses found that digoxin use was associated with a greater risk for all-cause mortality in patients aged ≥65 years with AF regardless of concomitant HF. Large, multicenter, randomized controlled trials or prospective cohort studies are required to clarify this issue.

Urotensin II (UII) is a vasoactive peptide with various roles in cardiovascular physiology and pathophysiology. There is an accumulating evidence implicating UII in atherosclerosis and coronary artery disease, making it an important target in acute coronary syndrome (ACS). In this study, we sought to determine the plasma levels of UII in ACS patients within 48 h of clinical presentation and after a 12-week recovery period. We compared them to patients with stable coronary artery disease (CAD) and a control group of normolipidemic subjects without known CAD. Using a highly sensitive ELISA technique, we measured plasma UII in 27 ACS patients, 26 stable CAD patients and 22 age-matched controls. ACS patients had significantly elevated plasma UII during the first 48 h of clinical presentation compared to stable CAD patients and controls. We also found significant positive correlations between UII and CRP and with triglycerides and a significant negative correlation between UII and EF. There was no correlation with LDL-C. In conclusion, plasma UII levels were elevated in patients with acute coronary syndrome, particularly immediately after clinical presentation. This suggests an upregulation of UII expression in ACS.

While awaiting randomized controlled trials to guide clinical practice, our study [(1)][1] is of benefit to better understand oral anticoagulation (OAC) following secondary atrial fibrillation (AF) associated with acute coronary syndrome (ACS), acute pulmonary disease, and sepsis. We used the

The clinical benefit of anticoagulation in secondary atrial fibrillation (AF) remains unclear. In our study [(1)][1], we did not demonstrate benefit of oral anticoagulation (OAC) therapy in stroke reduction in patients who develop secondary AF associated with acute coronary syndromes, acute

Young women (≤55 years) experiencing acute coronary syndrome (ACS) have poorer adverse outcomes like recurrent ACS than men. Sex differences have also been reported in response to antiplatelet medications such as clopidogrel. Polymorphisms in genes coding for drug metabolism enzymes (cytochrome

While post-operative atrial fibrillation is associated with a high incidence of long-term thromboembolic events, a lack of data exists to support an anticoagulation strategy in non-cardiac surgical patients. We aim to determine if anticoagulation use is associated with a reduction in thromboembolic

Patients with cardiovascular disease are increasingly exposed to low-dose ionizing radiation (LDIR) from diagnostic and therapeutic procedures. Previous studies have suggested that the malignancy risk associated with LDIR may be greatest in women and in young patients. We sought to compare the effect of LDIR on incident cancer across gender and age strata in a population-based cohort of patients with myocardial infarction (MI). All initially cancer-free patients with MI from 1996 to 2006 were identified in a province-wide administrative database. Procedure-specific LDIR dose estimates were used to generate a cumulative cardiac LDIR exposure variable. Time-dependent multivariate Cox regression was used to determine the relation between cardiac LDIR and incident cancer. A time-lag covariate of 3 years was used wherein a de novo cancer could only be attributed to LDIR incurred at least 3 years earlier. The effect of age and gender on LDIR-associated risk of cancer was evaluated with stratified models and the addition of interaction terms. The study cohort consisted of 56,606 men and 26,255 women. For each millisievert of cardiac LDIR, women were more likely to develop a cancer (hazard ratio 1.005, 95% confidence interval 1.002 to 1.008) than men (hazard ratio 1.002, 95% confidence interval 1.001 to 1.004) after adjusting for age, noncardiac LDIR, and covariates (p for interaction = 0.014). Contrarily, over the range studied (predominantly patients aged >50 years), age was not a determinant of LDIR-associated risk of cancer. In conclusion, women exposed to LDIR from cardiac imaging and therapeutic procedures after MI are at a greater risk of incident cancer compared with men after similar exposure. The extrapolated absolute risk from LDIR exposure would nonetheless be expected to be low.

Objectives: The study objectives were to analyze sex differences in hospital mortality of adult patients with congenital heart disease (CHD) and to determine the impact of health services associate...

Background The Canadian Cardiology Society recommends that patients should be seen within 2 weeks after an emergency department (ED) visit for heart failure (HF). We sought to investigate whether patients who had an ED visit for HF subsequently consult a physician within the current established benchmark, to explore factors related to physician consultation, and to examine whether delay in consultation is associated with adverse events (AEs) (death, hospitalization, or repeat ED visit). Methods Patients were recruited by nurses at 8 hospital EDs in Quebec, Canada, and interviewed by telephone within 6 weeks of discharge and subsequently at 3 and 6 months. Clinical variables were extracted from medical charts by nurses. We used Cox regression in the analysis. Results We enrolled 410 patients (mean age 74.9 ± 11.1 years, 53% males) with a confirmed primary diagnosis of HF. Only 30% consulted with a physician within 2 weeks post-ED visit. By 4 weeks, 51% consulted a physician. Over the 6-month follow-up, 26% returned to the ED, 25% were hospitalized, and 9% died. Patients who were followed up within 4 weeks were more likely to be older and have higher education and a worse quality of life. Patients who consulted a physician within 4 weeks of ED discharge had a lower risk of AEs (hazard ratio 0.59, 95% CI 0.35-0.99). Conclusion Prompt follow-up post-ED visit for HF is associated with lower risk for major AEs. Therefore, adherence to current HF guideline benchmarks for timely follow-up post-ED visit is crucial.

Objectives The purpose of this study was to examine smoking cessation rates among smokers with AMI to determine whether bupropion, started in-hospital, is safe and can improve cessation rates at 1 year. Background Bupropion doubles quit rates in otherwise healthy smokers and patients with stable cardiovascular disease. Although 2 previous trials examined the use of bupropion in patients hospitalized with acute cardiovascular disease, these studies have been inconclusive with respect to its safety and efficacy in patients with acute myocardial infarction (AMI). Methods We conducted a multicenter, double-blind, placebo-controlled, randomized trial in smokers hospitalized with AMI. Participants received bupropion or placebo for 9 weeks and were followed for 12 months. Both groups received low-intensity counseling. Point prevalence abstinence was assessed by 7-day recall and biochemical validation of expired carbon monoxide. Results A total of 392 patients were randomized (mean age 53.9 ± 10.3 years); 83.5% were male; 64.9% had ST-segment elevation myocardial infarction). Patients smoked a mean of 23.2 ± 10.6 cigarettes/day for a mean of 32.9 ± 12.4 years. At 12 months, point prevalence abstinence rates were 37.2% in the bupropion group and 32.0% in the placebo group (p = 0.33; % difference after adjusting for between center differences 3.9%). Continuous abstinence rates were 26.8% and 22.2%, respectively (p = 0.34). Major adverse cardiac event rates were similar (13.0% vs. 11.0%, respectively; p = 0.64). Conclusions Two-thirds of patients return to smoking by 12 months after AMI. Bupropion is well tolerated and seems to be safe to use in the immediate post-AMI period. However, bupropion is not effective for smoking cessation in patients post-AMI. (Zyban as an Effective Smoking Cessation Aid for Patients Following an Acute Coronary Syndrome: The ZESCA Trial; NCT00689611 )

Background Acupuncture, hypnotherapy, and aversive smoking are the most frequently studied alternative smoking cessation aids. These aids are often used as alternatives to pharmacotherapies for smoking cessation; however, their efficacy is unclear. Methods We carried out a random effect meta-analysis of randomized controlled trials to determine the efficacy of alternative smoking cessation aids. We systematically searched the Cochrane Library, EMBASE, Medline, and PsycINFO databases through December 2010. We only included trials that reported cessation outcomes as point prevalence or continuous abstinence at 6 or 12 months. Results Fourteen trials were identified; 6 investigated acupuncture (823 patients); 4 investigated hypnotherapy (273 patients); and 4 investigated aversive smoking (99 patients). The estimated mean treatment effects were acupuncture (odds ratio [OR], 3.53; 95% confidence interval [CI], 1.03-12.07), hypnotherapy (OR, 4.55; 95% CI, 0.98-21.01), and aversive smoking (OR, 4.26; 95% CI, 1.26-14.38). Conclusion Our results suggest that acupuncture and hypnotherapy may help smokers quit. Aversive smoking also may help smokers quit; however, there are no recent trials investigating this intervention. More evidence is needed to determine whether alternative interventions are as efficacious as pharmacotherapies.

Cardiac syndrome X (CSX) continues to be a mystery for clinicians who see patients with symptoms suggestive of obstructive coronary disease but who in fact lack evidence of coronary obstruction. Mysterious, this syndrome also stands out by the fact that it appears to preferentially affect women. In this supplement issue of the Canadian Journal of Cardiology (CJC) focused on persistent cardiac pain, CSX rightly deserves discussion by Arthur et al., alongside other outstanding topics in cardiology, such as mechanisms of cardiac pain (Rosen), classification of nonrevascularizable patients (Jolicoeur et al.), refractory angina management (McGillion et al.), and the continued problem, impact, and management of stable angina (Parker). While Arthur et al. provide a comprehensive coverage of the current state of our knowledge of CSX, we, in this editorial, would like to emphasize some of the points raised regarding CSX in the hope of helping to demystify this syndrome and provide a useful roadmap for the future. The American Heart Association has estimated that over 9 million people in the United States suffer from angina pectoris, which significantly impacts quality of life, ability to work, and costs to society. Within this group of people, a large number suffer a condition called CSX. The first description of patients with angina pectoris and normal coronary arteries appeared in 1967 and was followed by more reports. Arbogast and Bourassa described 10 patients with a definite electrocardiogram ischemic pattern during atrial pacing, typical or atypical angina pectoris, and normal or near normal coronary arteriograms, and labelled them as group X. In 1973, describing this patient group, Kemp first used the name syndrome X. Ingrained in its definition almost half a century ago, the mystery of this syndrome still continues to challenge our understanding of its mechanisms and hence few avenues for treatment have been proposed. CSX is a condition that causes angina or angina-like chest pain with exertion. It is characterized by an ST-segment depression on treadmill exercise testing, but normal coronary arteriography, with no spontaneous or inducible epicardial coronary artery spasm on ergonovine or acetylcholine provocation

Estimates from clinical trials and small observational studies of the incidence of pulmonary toxicity (PT) associated with amiodarone range from 1% to 10%. We report a unique study of the population-based incidence and potential predictors of PT in a real-world atrial fibrillation (AF) population. We conducted a retrospective cohort study of patients ≥65 years old discharged with AF using linked administrative databases from Quebec, Canada from 1999 to 2007. "Users" and "nonusers" of amiodarone were identified by prescriptions dispensed within 7 days after hospital discharge. PT was defined through International Classification of Diseases, Ninth Revision and Tenth Revision codes for pulmonary fibrosis, alveolar/interstitial lung disease, and adult respiratory distress syndrome. Potential risk factors for PT were identified using multivariable Cox regression. PT occurred in 250 of 6,460 amiodarone users (3.87%) and 676 of 50,993 nonusers (1.33%). Age-standardized PT incidences were 28.30 and 16.02 per 1,000 person-years in men and women users, respectively, and 14.05 and 8.82 per 1,000 person-years in nonusers, respectively. It was associated with amiodarone exposure at all doses (≤200 mg/day, hazard ratio 1.62, 1.35 to 1.96; >200 mg/day, 1.46, 1.22 to 1.75). Other predictors of PT included increasing age (1.01 per year, 1.00 to 1.02), male gender (1.37, 1.19 to 1.57), chronic obstructive pulmonary disease (2.53, 2.21 to 2.89), and renal disease (1.26, 1.06 to 1.50). In conclusion, the population-based incidence of amiodarone PT is in the lower range of what has been previously reported. However, patients with AF who use amiodarone have an approximately 50% higher risk of PT than nonusers. Clinicians may be able to use the present results to identify patients at higher risk for PT and implement strategies to increase monitoring or select alternative therapy.

Objectives The study sought to measure the prevalence, disease burden, and determinants of mortality in geriatric adults with congenital heart disease (ACHD). Background The population of ACHD is increasing and aging. The geriatric ACHD population has yet to be characterized. Methods Population-based cohort study using the Quebec Congenital Heart Disease Database of all patients with congenital heart disease coming into contact with the Quebec healthcare system between 1983 and 2005. Subjects with specific diagnoses of congenital heart disease and age 65 years at time of entry into the cohort were followed for up to 15 years. The primary outcome was all-cause mortality. Results The geriatric ACHD cohort consisted of 3,239 patients. From 1990 to 2005, the prevalence of ACHD in older adults remained constant from 3.8 to 3.7 per 1,000 indexed to the general population (prevalence odds ratio: 0.98; 95% confidence interval [CI]: 0.93 to 1.03). The age-stratified population prevalence of ACHD was similar in older and younger adults. The most common types of congenital heart disease lesions in older adults were shunt lesions (60%), followed by valvular lesions (37%) and severe congenital heart lesions (3%). Type of ACHD and ACHD-related complications had a minor impact on mortality, which was predominantly driven by acquired comorbid conditions. The most powerful predictors of mortality in the Cox proportional hazards model were: dementia (hazard ratio [HR]: 3.24; 95% CI: 1.53 to 6.85), gastrointestinal bleed (HR: 2.79; 95% CI: 1.66 to 4.69), and chronic kidney disease (HR: 2.50; 95% CI: 1.72 to 3.65). Conclusions The prevalence of geriatric ACHD is substantial, although severe lesions remain uncommon. ACHD patients that live long enough acquire general medical comorbidities, which are the pre-eminent determinants of their mortality.

Background Hospitalizations for atrial fibrillation (AF) impose a substantial burden on our health care system, and AF management strategies are increasingly focused on hospitalization reduction. The objectives of this study were to determine the cost of hospitalization for AF and to identify the main determinants of this cost in a Canadian setting. Methods Our study population consisted of patients hospitalized for AF and/or atrial flutter at a tertiary care hospital in Canada between April 1, 2001, and March 31, 2007. Patient-level demographics and data on clinical resource use and cost of treatment were collected from a computerized resource use and cost accounting system. The main determinants of in-hospital costs were identified through Bayesian model averaging. Results Data were collected on 325 consecutive hospitalizations for AF. The median length of stay was 5 days (interquartile range [IQR], 3-9). The mean cost of an AF admission was CAD$4740 (SD = CAD$4457), and the median was CAD$3532 (IQR, CAD$2013-CAD$5944). Multivariate analysis identified 2 independent predictors of increased cost: CHADS 2 score (relative increase in cost: 1.24; 95% CI, 1.16-1.33) and warfarin use (relative increase in cost: 1.41; 95% CI, 1.20-1.67). These 2 variables were also independent predictors of increased length of stay. Conclusions The main clinical determinants of increased cost and increased length of stay were CHADS 2 score and warfarin use. Strategies for reducing AF-related costs should focus on preventing hospitalization or decreasing its length in patients with high CHADS 2 scores and on finding alternatives to the use of warfarin or using outpatient bridging anticoagulation to facilitate earlier hospital discharge.

Objectives The aim of this study was to assess the impact of the diagnosis of pulmonary hypertension (PH) on mortality, morbidity, and health services utilization (HSU) in an adult congenital heart disease (CHD) population. Background Although PH is a well-recognized complication of CHD, population-based studies of its significance on the survival and functional capacity of patients are uncommon. Methods A retrospective longitudinal cohort study was conducted in an adult CHD population with 23 years of follow-up, from 1983 to 2005. The prevalence of PH was measured in 2005. Mortality, morbidity, and HSU outcomes were compared between patients with and without diagnoses of PH using multivariate Cox (mortality and morbidity) and Poisson (HSU) regression models within a subcohort matched for age and CHD lesion type. Results Of 38,430 adults alive with CHD in 2005, 2,212 (5.8%) had diagnoses of PH (median age 67 years, 59% women). The diagnosis of PH increased the all-cause mortality rate of adults with CHD more than 2-fold compared with patients without PH (hazard ratio [HR]: 2.69; 95% confidence interval [CI]: 2.41 to 2.99). Morbid complications including heart failure and arrhythmia occurred with a 3-fold higher risk compared with patients without PH (HR: 3.01; 95% CI: 2.80 to 3.22). The utilization of inpatient and outpatient services was increased, especially cardiac catheterization, excluding the index diagnostic study (rate ratio: 5.04; 95% CI: 4.27 to 5.93) and coronary and intensive care hospitalizations (rate ratio: 5.03; 95% CI: 4.86 to 5.20). Conclusions A diagnosis of PH in adults with CHD is associated with a more than 2-fold higher risk for all-cause mortality and 3-fold higher rates of HSU, reflecting high morbidity.

Background: Although prevalence of heart failure (HF) is similar in women and men, more men are admitted to specialized HF clinics, possibly owing to a perception that men benefit more. Our aim was to describe 1-year outcomes in men and women attending specialized HF clinics. Methods and Results: We enrolled 531 newly referred patients (mean age 66 years, 26% women) to 1 of 6 HF multidisciplinary clinics in Quebec. Data were collected at time of entry to the clinic and 6 and 12 months later. The 3 main outcomes, mortality, disease evolution (New York Heart Association functional class, quality of life, 6-minute walk), and number of hospital admissions/emergency department visits were analyzed separately. Survival was higher in women than in men (adjusted hazard ratio 2.53, 95% confidence interval 1.10e5.80). Both women and men improved over the 12-month period in terms of quality of life, 6-minute walk, and lower use of hospital and emergency department. Persons who at entry to the clinic had more severe disease showed more improvement. Deterioration over the year was associated with higher number of comorbidities, but not with age or gender. Conclusions: Both men and women with HF who attend specialized HF clinics improved, including those with more severe disease. (J Cardiac Fail 2011;17:540e546)

Background We compared severity of heart failure (HF) between men and women at entry to the multidisciplinary HF clinic based on 3 measures: New York Heart Association functional class, norm-referenced 6-minute walk distance, and health-related quality of life. Methods Newly admitted patients to 1 of 6 HF clinics were enrolled. Data were collected from a clinical database, questionnaires were administered to patients, and tests were administered by clinic nurses. We compared men and women with respect to the 3 severity indicators at entry to the clinic. Results In adjusted analyses, women had a lower health-related quality of life ( P = 0.04) but did not have lower norm-referenced 6-minute walk distance or lower New York Heart Association functional class on entry to the clinic. Having more comorbid conditions, being on medication, and having visited the emergency department or been admitted to hospital in the past 6 months were associated with higher severity at entry according to all 3 indicators. Conclusions Women report a lower health-related quality of life at entry to the clinic, although functional capacity does not seem to differ between women and men. Reasons for these discrepancies will need to be elucidated to better address women's health needs.

The long-term use of β blockers has been shown to improve the outcomes of patients with heart failure (HF). However, it is still disputed whether this is a class effect, and, specifically, whether carvedilol or bisoprolol are superior to metoprolol. The present study was a comparative effectiveness study of β blockers for patients with HF in a population-based setting. We conducted an observational cohort study using the Quebec administrative databases to identify patients with HF who were prescribed a β blocker after the diagnosis of HF. We used descriptive statistics to characterize the patients by the type of β blocker prescribed at discharge. The unadjusted mortality for users of each β blocker was calculated using Kaplan-Meier curves and compared using the log-rank test. To account for differences in follow-up and to control for differences among patient characteristics, a multivariate Cox proportional hazards model was used to compare the mortality. Of the 26,787 patients with HF, with a median follow-up of 1.8 years per patient, the crude incidence of death was 47% with metoprolol, 40% with atenolol, 41% with carvedilol, 36% with bisoprolol, and 43% with acebutolol. After controlling for several different covariates, we found that carvedilol (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.97 to 1.12, p = 0.22) and bisoprolol (HR 0.96, 95% CI 0.91 to 1.01, p = 0.16) were not superior to metoprolol in improving survival. Atenolol (HR 0.82, 95% CI 0.77 to 0.87, p

Background The congenital heart disease population is aging. We hypothesized that changes in rates of congenital, valvular, and noncongenital surgical operations in congenital heart patients varied with age and disease severity over the last two decades. Methods We performed time trend analysis using a Quebec congenital heart disease database constructed from administrative data. We included congenital heart patients of all ages having cardiac surgical operations. Heart lesions were classified as "severe" and "other." Cardiac surgical operations were grouped as congenital, valvular (including aortic), and noncongenital (arrhythmia surgery, coronary artery bypass grafting, and cardiac transplants). An adapted Aristotle score was developed to classify procedures based on surgical risk. Yearly surgical rates were measured as surgical operations per 1,000 person-years and analyzed over time using Poisson regression models stratified by age, lesion severity, and cardiac surgery category. Results From 1988 to 2005 we followed 71,979 patients for 1,009,430 person-years. We identified 17,444 cardiac surgical operations. There was a 31% increase in volumes and a 5% increase in surgical rates over time. In children, congenital surgical operations remained constant, accounting for 80% of all surgical operations. In adults, valvular operations were the most common type of surgical operations, increasing from 42% to 63% of all procedures over time. Rates of valvular operations increased significantly in all adult subgroups and in children with severe lesions. Conclusions The need for valvular interventions has increased in the last two decades in congenital heart disease patients. These findings should be taken into account when allocating resources that will optimize outcomes for this growing population.

Background The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized controlled trial that studied 9361 adults ≥50 years of age with systolic blood pressure >130 mm Hg and ≥1 cardiovascular risk factors. Patients were randomized to intensive (≤120 mm Hg) or standard (≤140 mm Hg) systolic targets. In August 2016, a limited dataset was released for secondary analysis. We hypothesized that excessive lowering of diastolic blood pressure could cause harm. Using the data from SPRINT, we sought to determine whether the development of diastolic hypotension during treatment was associated with adverse outcomes. Methods We included 8046 patients from SPRINT with a baseline diastolic blood pressure ≥65 mm Hg at study enrollment (4041 intensive target; 4005 standard target). Using Cox proportional hazards models, we evaluated the association between the development of diastolic hypotension (defined as ≤55 mm Hg and modeled as a time-dependent covariate) and the combined outcome of cardiovascular morbidity (myocardial infarction, other acute coronary syndromes, stroke, heart failure) and all-cause death. Results In multivariable analyses, patients who developed diastolic hypotension had an increased risk for our primary outcome (hazard ratio [HR] 1.67; 95% confidence interval [CI] 1.24-2.26). This was true in both the intensive (HR 1.53; 95% CI, 1.04-2.26) and standard (HR 2.23; 95% CI, 1.40-3.54; P for interaction = .09) treatment arms. Conclusions We found an association between diastolic hypotension and the combined endpoint of cardiovascular events and all-cause mortality among SPRINT participants with normal to high diastolic blood pressure at entry. Attention to diastolic blood pressure may be important for optimizing outcomes when targeting systolic blood pressure reduction.

Conclusions The metabolic syndrome is associated with a 2-fold increase in cardiovascular outcomes and a 1.5-fold increase in all-cause mortality. Studies are needed to investigate whether or not the prognostic significance of the metabolic syndrome exceeds the risk associated with the sum of its individual components. Furthermore, studies are needed to elucidate the mechanisms by which the metabolic syndrome increases cardiovascular risk. (J Am Coll Cardiol 2010;56:1113‐32) © 2010 by the American College of Cardiology Foundation

Atrial arrhythmias (AAs) are a common complication in adult patients with congenital heart disease. We sought to compare the lifetime prevalence of AAs in patients with right- versus left-sided congenital cardiac lesions and their effect on the prognosis. A congenital heart disease diagnosis was assigned using the International Disease Classification, Ninth Revision, diagnostic codes in the administrative databases of Quebec, from 1983 to 2005. Patients with AAs were those diagnosed with an International Disease Classification, Ninth Revision, code for atrial fibrillation or intra-atrial reentry tachycardia. To ensure that the diagnosis of AA was new, a washout period of 5 years after entry into the database was used, a period during which the patient could not have received an International Disease Classification, Ninth Revision, code for AA. The cumulative lifetime risk of AA was estimated using the Practical Incidence Estimators method. The hazard ratios (HRs) for mortality, morbidity, and cardiac interventions were compared between those with right- and left-sided lesions after adjustment for age, gender, disease severity, and cardiac risk factors. In a population of 71,467 patients, 7,756 adults developed AAs (isolated right-sided, 2,229; isolated left-sided, 1,725). The lifetime risk of developing AAs was significantly greater in patients with right- sided than in patients with left-sided lesions (61.0% vs 55.4%, p0.001). The HR for mortality and the development of stroke or heart failure was similar in both groups (HR 0.96, 95% confidence interval [CI] 0.86 to 1.09; HR 0.94, 95% CI 0.80 to 1.09; and HR 1.10, 95% CI 0.98 to 1.23, respectively). However, the rates of cardiac catheterization (HR 0.63, 95% CI 0.55 to 0.72), cardiac surgery (HR 0.40, 95% CI 0.36 to 0.45), and arrhythmia surgery (HR 0.77, 95% CI 0.6 to 0.98) were significantly less for patients with right-sided lesions. In conclusion, patients with right-sided lesions had a greater lifetime burden of AAs. However, their morbidity and mortality were no less than those with left-sided lesions, although the rate of intervention was substantially different.

Introduction Several meta-analyses have examined the efficacy of smoking cessation therapies in the general population. However, little is known about the efficacy of these therapies in cardiac patients. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to determine the efficacy of behavioural therapy and pharmacotherapy for smoking cessation in cardiac patients. Methods The medical literature was systematically reviewed to identify smoking cessation RCTs in cardiac patients. Only RCTs that reported smoking abstinence at six or 12 months were included. Smoking abstinence was examined based on the ‘most rigorous criterion', defined as the most conservative outcome reported in any given RCT. Results Eleven behavioural therapy RCTs that enrolled 2105 patients and four pharmacotherapy RCTs that enrolled 1542 patients were identified. RCTs differed in the type of behavioural therapy administered as well as the total length and duration of the intervention. RCTs differed in the type of pharmacotherapy administered (one nicotine patch RCT, one nicotine gum RCT and two bupropion RCTs). Behavioural therapy was associated with a significantly higher proportion of smoking abstinence than usual care (OR 1.97 [95% CI 1.37 to 2.85]). Pharmacotherapies were more efficacious than placebo (pooled OR 1.72 [95% CI 1.15 to 2.57]). Conclusions Both behavioural therapy and pharmacotherapy are more efficacious than usual care for smoking cessation in cardiac patients. The present meta-analysis highlights the need for head-to-head RCTs to identify which smoking cessation therapy is preferred in cardiac patients as well as RCTs examining the efficacy of combined behavioural and pharmacotherapies.

Background Congestive heart failure (CHF) is a common cause of hospitalization and has a poor prognosis. Specialized multidisciplinary clinics are effective in the management of CHF. Objectives To measure time of admission to the specialized clinics and explore factors related to the time of admission to these clinics. Methods Patients who were newly admitted to one of six CHF multidisciplinary clinics in the province of Quebec were enrolled in the study. Data were collected from the common clinical database used at these clinics as well as from questionnaires administered to the patients. Results A total of 531 patients with a mean age of 65.9 years were enrolled. Only 26% were women. The median duration of disease before admission to the CHF clinic was 1.2 years. The majority of patients (62%) were referred by a cardiologist or an internist, while 24% were referred by other specialists, and 14% by general practitioners. One-fifth of patients did not have regular follow-up for their CHF before being admitted to the clinic. Factors associated with shorter disease duration at admission to the clinic were referral by a specialist, not having regular medical follow-up for CHF, having a higher income and having visited the emergency room for CHF. Conclusion There may be a need to improve dissemination of information regarding availability and benefits of CHF clinics and criteria for referral.

A functional screen of an adenovirus-delivered shRNA library that targets approximately 4500 host genes was performed to identify cellular factors that regulate hepatitis C virus (HCV) sub-genomic RNA replication. Seventy-three hits were further examined by siRNA oligonucleotide-directed knockdown, and silencing of the PI4KA gene was demonstrated to have a significant effect on the replication of a HCV genotype 1b replicon. Using transient siRNA oligonucleotide transfections and stable shRNA knockdown clones in HuH-7 cells, the PI4KA gene was shown to be essential for the replication of all HCV genotypes tested (1a, 1b and 2a) but not required for bovine viral diarrhea virus (BVDV) RNA replication.