Antigone Oreopoulos

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.

Risk factor paradox in wasting diseases.

Purpose of reviewEmerging data indicate that conventional cardiovascular risk factors (e.g. hypercholesterolemia and obesity) are paradoxically associated with better survival in distinct populations with wasting. We identify these populations and review survival paradoxes and common pathophysiologic mechanisms. Recent findingsA ‘reverse epidemiology’ of cardiovascular risk is observed in chronic kidney disease, chronic heart failure, chronic obstructive lung disease, cancer, AIDS and rheumatoid arthritis, and in the elderly. These populations apparently have slowly progressive to full-blown wasting and significantly greater short-term mortality than the general population. The survival paradoxes may result from the time differential between the two competing risk factors [i.e. over-nutrition (long-term killer but short-term protective) versus undernutrition (short-term killer)]. Hemodynamic stability of obesity, protective adipokine profile, endotoxin–lipoprotein interaction, toxin sequestration of fat, antioxidation of muscle, reverse causation, and survival selection may also contribute. SummaryThe seemingly counterintuitive risk factor paradox is the hallmark of chronic disease states or conditions associated with wasting disease at the population level. Studying similarities among these populations may help reveal common pathophysiologic mechanisms of wasting disease, leading to a major shift in clinical medicine and public health beyond the conventional Framingham paradigm and to novel therapeutic approaches related to wasting and short-term mortality.

The Obesity Paradox and Mortality Associated With Surrogates of Body Size and Muscle Mass in Patients Receiving Hemodialysis

OBJECTIVE To determine whether dry weight gain accompanied by an increase in muscle mass is associated with a survival benefit in patients receiving maintenance hemodialysis (HD). PATIENTS AND METHODS In a nationally representative 5-year cohort of 121,762 patients receiving HD 3 times weekly from July 1, 2001, through June 30, 2006, we examined whether body mass index (BMI) (calculated using 3-month averaged post-HD dry weight) and 3-month averaged serum creatinine levels (a likely surrogate of muscle mass) and their changes over time were predictive of mortality risk. RESULTS In the cohort, higher BMI (up to 45) and higher serum creatinine concentration were incrementally and independently associated with greater survival, even after extensive multivariate adjustment for available surrogates of nutritional status and inflammation. Dry weight loss or gain over time exhibited a graded association with higher rates of mortality or survival, respectively, as did changes in serum creatinine level over time. Among the 50,831 patients who survived the first 6 months and who had available data for changes in weight and creatinine level, those who lost weight but had an increased serum creatinine level had a greater survival rate than those who gained weight but had a decreased creatinine level. These associations appeared consistent across different demographic groups of patients receiving HD. CONCLUSION In patients receiving long-term HD, larger body size with more muscle mass appears associated with a higher survival rate. A discordant muscle gain with weight loss over time may confer more survival benefit than weight gain while losing muscle. Controlled trials of muscle-gaining interventions in patients receiving HD are warranted.

The Obesity Paradox in the Elderly: Potential Mechanisms and Clinical Implications

The prevalence of overweight and obesity in the elderly has become a growing concern. Recent evidence indicates that in the elderly, obesity is paradoxically associated with a lower, not higher, mortality risk. Although obesity in the general adult population is associated with higher mortality, this relationship is unclear for persons of advanced age and has lead to great controversy regarding the relationship between obesity and mortality in the elderly, the definition of obesity in the elderly, and the need for its treatment in this population. This article examines the evidence on these controversial issues, explores potential explanations for these findings, discusses the clinical implications, and provides recommendations for further research in this area.

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).

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

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.

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

Aims Our objective was to examine the association between body mass index (BMI) and survival according to the type of treatment in individuals with established coronary artery disease (CAD). Methods and results Patients with CAD were identified in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry between January 2001 and March 2006. Analyses were conducted separately by treatment strategy [medical management only, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]. Patients were grouped according to six BMI categories. Multivariable-adjusted hazard ratios (HRs) for mortality were calculated using the Cox regression with the referent group for all analyses being normal BMI (18.5-24.9 kg/m(2)). The cohort included 31 021 patients with a median follow-up time of 46 months. In the medically managed only group, BMIs of 25.0-29.9 and 30.0-34.9 kg/m(2) were associated with significantly lower mortality compared with normal BMI patients (adjusted HR 0.72; 95% CI 0.63-0.83 and adjusted HR 0.82; 95% CI 0.69.0-0.98, respectively). In the CABG group, BMI of 30.0-34.9 kg/m(2) had the lowest risk of mortality (adjusted HR 0.75; 95% CI 0.61-0.94), whereas in the PCI group, BMI of 35.0-39.9 kg/m(2) had the lowest risk of mortality (adjusted HR 0.65; 95% CI 0.47-0.90). Patients who were overweight or have mild or moderate obesity were also more likely to undergo revascularization procedures compared with those with normal BMI, despite having lower risk coronary anatomy. Conclusion A paradoxical association between BMI and survival exists in patients with established CAD irrespective of treatment strategy. Patients with obesity may be presenting earlier and receiving more aggressive treatment compared with those with normal BMI.

Comparing body composition assessment tests in long-term hemodialysis patients.

BACKGROUND Protein-energy wasting is common in chronic kidney disease and is associated with decreases in body muscle and fat stores and poor outcomes. The accuracy and reliability of field methods to measure body composition is unknown in this population. STUDY DESIGN Cross-sectional observational study. SETTING & PARTICIPANTS 118 maintenance hemodialysis patients were seen at the General Clinical Research Center at Harbor-UCLA Medical Center, Torrance, CA. INDEX TESTS Triceps skinfold, near-infrared interactance, and bioelectrical impedance analysis using the Segal, Kushner, and Lukaski equations. REFERENCE TEST Dual-energy x-ray absorptiometry (DEXA). RESULTS Participants (42% women, 52% with diabetes, 40% African Americans, and 38% Hispanics) were aged 49.4 +/- 11.5 (mean +/- SD) years, and had undergone dialysis therapy for 41.1 +/- 32.9 months. Body mass index was 27.0 +/- 6.0 kg/m(2). Using DEXA as the reference test, the bioelectrical impedance analysis-Kushner equation, triceps skinfold, and near-infrared interactance were most accurate of the index tests in estimating total-body fat percentage, whereas bioelectrical impedance analysis-Segal equation and bioelectrical impedance analysis-Lukaski equation overestimated total body fat percentage. Bland-Altman analyses and difference plots showed that bioelectrical impedance analysis-Kushner and near-infrared interactance were most similar to the reference test. Bioelectrical impedance analysis-Kushner, triceps skinfold, and near-infrared interactance had the smallest mean differences from DEXA, especially in women (1.6%, 0.7%, and 1.2%, respectively). Similar results were observed in African American participants (n = 47). LIMITATIONS Measurements were performed 1 day after a hemodialysis treatment, leading to more fluid retention, which may have affected the reference and index tests differently. CONCLUSIONS Using DEXA as the reference test, both near-infrared interactance and bioelectrical impedance analysis-Kushner method yield more consistent estimates of total body fat percentage in maintenance hemodialysis patients compared with the other index tests. Near-infrared interactance is not affected by skin color. Field methods with portable devices may provide adequate precision.

Novel Equations to Estimate Lean Body Mass in Maintenance Hemodialysis Patients

BACKGROUND Lean body mass (LBM) is an important nutritional measure representing muscle mass and somatic protein in hemodialysis patients, for whom we developed and tested equations to estimate LBM. STUDY DESIGN A study of diagnostic test accuracy. SETTING & PARTICIPANTS The development cohort included 118 hemodialysis patients with LBM measured using dual-energy x-ray absorptiometry (DEXA) and near-infrared (NIR) interactance. The validation cohort included 612 additional hemodialysis patients with LBM measured using a portable NIR interactance technique during hemodialysis. INDEX TESTS 3-month averaged serum concentrations of creatinine, albumin, and prealbumin; normalized protein nitrogen appearance; midarm muscle circumference (MAMC); handgrip strength; and subjective global assessment of nutrition. REFERENCE TEST LBM measured using DEXA in the development cohort and NIR interactance in validation cohorts. RESULTS In the development cohort, DEXA and NIR interactance correlated strongly (r = 0.94, P < 0.001). DEXA-measured LBM correlated with serum creatinine level, MAMC, and handgrip strength, but not with other nutritional markers. Three regression equations to estimate DEXA-measured LBM were developed based on each of these 3 surrogates and sex, height, weight, and age (and urea reduction ratio for the serum creatinine regression). In the validation cohort, the validity of the equations was tested against the NIR interactance-measured LBM. The equation estimates correlated well with NIR interactance-measured LBM (R² ≥ 0.88), although in higher LBM ranges, they tended to underestimate it. Median (95% confidence interval) differences and interquartile range for differences between equation estimates and NIR interactance-measured LBM were 3.4 (-3.2 to 12.0) and 3.0 (1.1-5.1) kg for serum creatinine and 4.0 (-2.6 to 13.6) and 3.7 (1.3-6.0) kg for MAMC, respectively. LIMITATIONS DEXA measurements were obtained on a nondialysis day, whereas NIR interactance was performed during hemodialysis treatment, with the likelihood of confounding by volume status variations. CONCLUSIONS Compared with reference measures of LBM, equations using serum creatinine level, MAMC, or handgrip strength and demographic variables can estimate LBM accurately in long-term hemodialysis patients.

Association between obesity and health-related quality of life in patients with coronary artery disease.

Background and Objective:In patients with coronary artery disease (CAD), obesity is paradoxically associated with better survival (the ‘obesity paradox’). Our objective was to determine whether this counterintuitive relationship extends to health-related quality of life (HRQOL) outcomes.Design:Cross-sectional observational study.Subjects:All adults undergoing coronary angiography residing in Alberta, Canada between January 2003 and March 2006 in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) registry.Methods:Patients completed self-reported questionnaires 1 year after their index cardiac catheterization, including the Seattle Angina Questionnaire (SAQ) and the EuroQol 5D (EQ-5D Index). Patients were grouped into six body mass index (BMI) categories (underweight, normal, overweight, mild obesity, moderate obesity and severe obesity). An analysis of covariance was used to create risk-adjusted scores.Results:A total of 5362 patients were included in the analysis. Obese patients were younger than normal and overweight participants, and had a higher prevalence of depression and cardiovascular risk factors. In the adjusted models, SAQ physical function scores and the EQ Index (representing overall QOL) were significantly reduced in patients with mild, moderate and severe obesity compared with patients with a normal BMI. Patients with severe obesity had both statistically and clinically significant reductions in HRQOL scores. Depressive symptoms accounted for a large proportion in variability of all HRQOL scores.Conclusions:BMI is inversely associated with physical function and overall HRQOL in CAD patients, especially in patients with severe obesity. High body weight is a modifiable risk factor; however, given the apparent obesity paradox in patients with CAD, it is critical that future studies be conducted to fully clarify the relationships between HRQOL and body composition (body fat and lean mass), nutritional state and survival outcomes.