Colleen M. Norris

Body mass index and mortality in heart failure: A meta-analysis

BACKGROUND In patients with chronic heart failure (CHF), previous studies have reported reduced mortality rates in patients with increased body mass index (BMI). The potentially protective effect of increased BMI in CHF has been termed the obesity paradox or reverse epidemiology. This meta-analysis was conducted to examine the relationship between increased BMI and mortality in patients with CHF. METHODS We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Scopus, and Web of Science to identify studies with contemporaneous control groups (cohort, case-control, or randomized controlled trials) that examined the effect of obesity on all-cause and cardiovascular mortality. Two reviewers independently assessed studies for inclusion and performed data extraction. RESULTS Nine observational studies met final inclusion criteria (total n = 28,209). Mean length of follow-up was 2.7 years. Compared to individuals without elevated BMI levels, both overweight (BMI approximately 25.0-29.9 kg/m(2), RR 0.84, 95% CI 0.79-0.90) and obesity (BMI approximately > or =30 kg/m(2), RR 0.67, 95% CI 0.62-0.73) were associated with lower all-cause mortality. Overweight (RR 0.81, 95% CI 0.72-0.92) and obesity (RR 0.60, 95% CI 0.53-0.69) were also associated with lower cardiovascular mortality. In a risk-adjusted sensitivity analysis, both obesity (adjusted HR 0.88, 95% CI 0.83-0.93) and overweight (adjusted HR 0.93, 95% CI 0.89-0.97) remained protective against mortality. CONCLUSIONS Overweight and obesity were associated with lower all-cause and cardiovascular mortality rates in patients with CHF and were not associated with increased mortality in any study. There is a need for prospective studies to elucidate mechanisms for this relationship.

A comprehensive view of sex-specific issues related to cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown.

Effect of obesity on short- and long-term mortality postcoronary revascularization: a meta-analysis.

Objective: Overweight and obesity are often assumed to be risk factors for postprocedural mortality in patients with coronary artery disease (CAD). However, recent studies have described an “obesity paradox”—a neutral or beneficial association between obesity and mortality postcoronary revascularization. We reviewed the effect of overweight and obesity systematically on short‐ and long‐term all‐cause mortality post‐coronary artery bypass grafting (CABG) and post‐percutaneous coronary intervention (PCI).

Sex Differences in Access to Coronary Revascularization after Cardiac Catheterization: Importance of Detailed Clinical Data

Context Women are less likely to be offered therapeutic cardiac procedures than men; however, the reasongender bias or clinical factorsis unknown. Contribution This study of coronary revascularization procedures during the year after catheterization compared men and women with the same extent of coronary artery disease and ejection fraction. The rate of coronary revascularization was the same in men and women. Implications The sex differences in cardiac procedure rates after catheterization appear to reflect appropriate decisions rather than gender bias. However, sex-based differences in catheterization rates remain unexplained. The Editors Reports of sex differences in the likelihood of undergoing cardiac procedures have led to suggestions of gender bias in cardiac care decision making (1-14). Other proposed explanations for the variation in use of cardiac procedures between sexes include differing patient preferences or differing clinical characteristics (for example, smaller coronary vessels in women). Earlier studies did not unanimously find sex differences in cardiac procedure rates; some studies reported equivalent procedure rates for men and women (15-21). The inconsistency across studies may be related to differences in geographic regions and health systems. However, another possible explanation is that many earlier studies evaluated highly selected patient samples that may not reflect processes of care at a population level. Yet another possible explanation is that the published studies on this issue have used various data sources, ranging from highly detailed data from clinical trials to sparsely detailed administrative data. The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) is a population-based registry that captures detailed clinical information on all adult patients undergoing cardiac catheterization in the province of Alberta, Canada (22). The clinically detailed data generated by APPROACH provide a unique opportunity to study sex differences in access to revascularization after cardiac catheterization without the limitations of a nonrepresentative study sample or insufficiently detailed clinical data. Furthermore, the detailed APPROACH data allow us to assess whether comorbid conditions, extent of coronary disease, and ejection fraction account for or explain any observed sex differences in access to revascularization procedurespercutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery. Using a two-step process, we statistically adjusted crude (unadjusted) rates of cardiac revascularization for men and women in the year following cardiac catheterization. The first (partial) adjustment was based on baseline clinical variables that are routinely available in most databases, including administrative databases. The second (full) adjustment also controlled for extent of coro nary disease and ejection fraction, variables that are uniquely available for a large unselected patient population in APPROACH data. Methods Data Source and Variables The APPROACH database is an inception cohort database that captures clinical information on all patients undergoing cardiac catheterization in Alberta, Canada (22). This province has a population of approximately 2.8 million persons, of whom 10% identify themselves as ethnic minorities (3.5% are of Chinese ethnicity, 2% are of South Asian ethnicity, 1% are black, and 4.5% are aboriginal inhabitants). In 1996, median individual income levels for postal codedefined regions ranged from

Association Between Direct Measures of Body Composition and Prognostic Factors in Chronic Heart Failure

12 000 to

Multiple imputation versus data enhancement for dealing with missing data in observational health care outcome analyses

37 000 Canadian per year. Sixty-seven percent of Albertans older than 20 years of age have a high school diploma, and 25% have some university-level education. Patients in APPROACH are followed longitudinally for assessment of long-term outcomes after cardiac catheterization. Clinical risk variables recorded at the time of cardiac catheterization are age, sex, diabetes mellitus, cerebrovascular disease, congestive heart failure, chronic pulmonary disease, elevated creatinine level ( 200 mmol/L [ 22.62 g/L]), dialysis status, hyperlipidemia, hypertension, liver or gastrointestinal disease, malignancy or metastatic disease, previous myocardial infarction, previous thrombolytic therapy for myocardial infarction, and peripheral vascular disease. The indication for catheterization is recorded in one of four categories: myocardial infarction within 8 weeks of catheterization, unstable angina, stable angina, or other (for example, arrhythmias without associated angina, or study protocols). The results of cardiac catheterization, including extent of coronary disease and left ventricular ejection fraction, are also recorded. We graded extent of coronary disease according to six categories: normal or near normal, one- to two-vessel disease, two-vessel disease with proximal left anterior descending artery involvement, three-vessel disease, three-vessel disease with proximal left anterior descending artery involvement, or left main disease. A diseased vessel was one that contained a lesion involving more than 50% of the vessel diameter. Left ventricular ejection fraction was graded according to five categories: greater than 50%, 30% to 50%, less than 30%, ventriculography not done (usually because of renal insufficiency or severely depressed cardiac function), and data missing. The APPROACH database accurately captures the occurrence of revascularization procedures in Alberta hospitals and the time to revascularization after cardiac catheterization. We analyzed data from patients undergoing cardiac catheterization from 1995 through 1998, with follow-up data through 1999. The Ethics Review Boards of the University of Calgary and the University of Alberta, Canada, approved the APPROACH study protocol. Statistical Analysis We performed a chi-square test and two-sample t-tests to compare the clinical characteristics of men and women undergoing catheterization. Chi-square tests and log-rank tests were used to compare the unadjusted proportions of men and women having revascularization procedures within 1 year after cardiac catheterization. We then used multivariable Cox proportional-hazards analyses to control revascularization rates for differences in clinical characteristics between men and women undergoing catheterization. For these analyses, we modeled time to 1) any revascularization procedure, 2) PCI, and 3) CABG surgery, with follow-up to 1 year. We initially calculated crude relative risks for procedures for women relative to men and then sequentially modeled two sets of variables. First, for the partially adjusted model, we used a set of clinical variables (age, indication for cardiac catheterization, cardiac history, and the comorbidity variables listed earlier) that would generally be available in most administrative databases (throughout the paper, we call this initial step partial adjustment). Second, for the fully adjusted model, we added two clinical variables, left ventricular ejection fraction and extent of coronary disease, that are uniquely available at a population level in the clinically detailed APPROACH database. The relative risk for women compared with men was the variable of interest for each of the models generated. We calculated and plotted risk-adjusted time-to-revascularization curves for men and women by applying the corrected group prognosis method to the proportional hazards models that generated fully adjusted relative risks (23). By plotting log[log S(t)] versus t and log(t) for all of the above models, we found that the proportional hazards assumption was appropriate for all variables included in the models, except the variable of indication for cardiac catheterization. Therefore, we handled cardiac catheterization as a stratification variable in our models. To assess model performance, we also plotted both martingale and deviance residuals for individual observations and found that none of the observations were widely deviant (that is, almost all deviance residuals were between 1.96 and 1.96). We examined influential observations by measuring the changes in the coefficients after dropping each observation from the data. For sex, the most influential observations changed the coefficient by less than 5% of the standard error. The software product used to perform data analyses was S-PLUS 5 for Linux, version 5.1 (Insightful Corp., Seattle, Washington). Role of the Funding Sources The funding sources had no role in the design, conduct, or reporting of this study. Results A total of 21 816 patients underwent cardiac catheterization in Alberta between 1 January 1995 and 31 December 1998. Of these patients, 15 409 (70.6%) were men and 6407 (29.4%) were women. Within 1 year after catheterization, 8488 of the 15 409 men (55.1%) had undergone a revascularization procedure (PCI or CABG surgery) compared with only 2574 of the 6407 women (40.2%) (P < 0.001). The proportion having undergone PCI at 1 year was 32.2% for men versus 26.1% for women (P < 0.001). The proportion having CABG surgery by 1 year after catheterization was 22.9% for men and only 14.0% for women (P < 0.001). In a proportional hazards analysis, the corresponding crude relative risk (that is, the likelihood) for having any revascularization procedure for women compared with men was 0.67 (95% CI, 0.65 to 0.71). For PCI and CABG surgery, the corresponding relative risks were 0.77 (CI, 0.73 to 0.82) and 0.54 (0.51 to 0.58), respectively. Thus, in relative terms, women were 33% less likely to undergo any revascularization procedure, 23% less likely to undergo PCI, and 46% less likely to undergo CABG surgery than were men. Clinical Characteristics Clinical characteristics of men and women differed (Table 1). Men tended to be younger and had fewer comorbid conditions, including a lower prevalence of chronic lung disease, cerebrovascular disease, hypertension, diabetes mellitus, liver disease, and congestive heart failure. However, men

Development and validation of a surname list to define Chinese ethnicity.

OBJECTIVE To explore the covariate-adjusted associations between body composition (percent body fat and lean body mass) and prognostic factors for mortality in patients with chronic heart failure (CHF) (nutritional status, N-terminal pro-B-type natriuretic peptide [NT-proBNP], quality of life, exercise capacity, and C-reactive protein). PATIENTS AND METHODS Between June 2008 and July 2009, we directly measured body composition using dual energy x-ray absorptiometry in 140 patients with systolic and/or diastolic heart failure. We compared body composition and CHF prognostic factors across body fat reference ranges and body mass index (BMI) categories. Multiple linear regression models were created to examine the independent associations between body composition and CHF prognostic factors; we contrasted these with models that used BMI. RESULTS Use of BMI misclassified body fat status in 51 patients (41%). Body mass index was correlated with both lean body mass (r=0.72) and percent body fat (r=0.67). Lean body mass significantly increased with increasing BMI but not with percent body fat. Body mass index was significantly associated with lower NT-proBNP and lower exercise capacity. In contrast, higher percent body fat was associated with a higher serum prealbumin level, lower exercise capacity, and increased C-reactive protein level; lean body mass was inversely associated with NT-proBNP and positively associated with hand-grip strength. CONCLUSION When BMI is divided into fat and lean mass components, a higher lean body mass and/or lower fat mass is independently associated with factors that are prognostically advantageous in CHF. Body mass index may not be a good indicator of adiposity and may in fact be a better surrogate for lean body mass in this population.

Sex Differences in Acute Coronary Syndrome Symptom Presentation in Young Patients

The problem of missing data is frequently encountered in observational studies. We compared approaches to dealing with missing data. Three multiple imputation methods were compared with a method of enhancing a clinical database through merging with administrative data. The clinical database used for comparison contained information collected from 6,065 cardiac care patients in 1995 in the province of Alberta, Canada. The effectiveness of the different strategies was evaluated using measures of discrimination and goodness of fit for the 1995 data. The strategies were further evaluated by examining how well the models predicted outcomes in data collected from patients in 1996. In general, the different methods produced similar results, with one of the multiple imputation methods demonstrating a slight advantage. It is concluded that the choice of missing data strategy should be guided by statistical expertise and data resources.

The relationship between body mass index, treatment, and mortality in patients with established coronary artery disease: a report from APPROACH.

Objective:Surnames have the potential to accurately identify ancestral origins as they are passed on from generation to generation. In this study, we developed and validated a Chinese surname list to define Chinese ethnicity. Methods:We conducted a literature review, a panel review, and a telephone survey in a randomly selected sample from a Canadian city in 2003 to develop a Chinese surname list. The list was then validated to data from the Canadian Community Health Survey. Both surveys collected information on self-reported ethnicity and surname. Results:Of the 112,452 people analyzed in the Canadian Community Health Survey, 1.6% were self-reported as Chinese. This was similar to the 1.5% identified by the surname list. Compared with self-reported Chinese ethnicity (reference standard), the surname list had 77.7% sensitivity, 80.5% positive predictive value, 99.7% specificity, and 99.6% negative predictive value. When stratifying by sex and marital status, the positive predictive value was 78.9% for married women and 83.6% for never married women. Conclusions:The Chinese surname list appears to be valid in identifying Chinese ethnicity. The validity may depend on the geographic origins and Chinese dialects in given populations.

ICU and non-ICU cost per day

IMPORTANCE Little is known about whether sex differences in acute coronary syndrome (ACS) presentation exist in young patients and what factors determine absence of chest pain in ACS presentation. OBJECTIVES To evaluate sex differences in ACS presentation and to estimate associations between sex, sociodemographic, gender identity, psychosocial and clinical factors, markers of coronary disease severity, and absence of chest pain in young patients with ACS. DESIGN, SETTING, PARTICIPANTS We conducted a prospective cohort study of 1015 patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September 2012). MAIN OUTCOMES AND MEASURES The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey was administered during hospitalization. RESULTS The median age for both sexes was 49 years. Women were more likely to have non-ST-segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without chest pain reported fewer symptoms overall and no discernable pattern of non-chest pain symptoms was found. In the multivariate model, being a woman (odds ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95% CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation without chest pain. Patients without chest pain did not differ significantly from those with chest pain in terms of ACS type, troponin level elevation, or coronary stenosis. CONCLUSIONS AND RELEVANCE Chest pain was the most common ACS symptom in both sexes. Although women were more likely to present without chest pain than men, absence of chest pain was not associated with markers of coronary disease severity. Strategies that explicitly incorporate assessment of common non-chest pain symptoms need to be evaluated.