Does Obesity Protect Against Death in Sepsis? A Retrospective Cohort Study of 55,038 Adult Patients*

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Abstract

Observational studies suggest obesity is associated with sepsis survival, but these studies are small, fail to adjust for key confounders, measure body mass index (BMI) at inconsistent time points, and/or use administrative data to define sepsis. To estimate the relationship between BMI and sepsis mortality using detailed clinical data for case detection and risk-adjustment. Retrospective cohort analysis of a large clinical data repository 139 hospitals in the United States of America Adult inpatients with sepsis meeting Sepsis-3 criteria BMI in six categories: underweight (BMI<18.5kg/m 2 ), normal-weight (BMI=18.5–24.9kg/m 2 ), overweight (BMI=25.0–29.9kg/m 2 ), obese-class-I (BMI=30.0–34.9kg/m 2 ), obese-class-II (BMI=35.0–39.9kg/m 2 ), and obese-class-III (BMI≥40kg/m 2 ). Multivariate logistic regression with generalized estimating equations to estimate the effect of BMI category on short-term mortality (in-hospital death or discharge to hospice) adjusting for patient, infection, and hospital-level factors. Sensitivity analyses were conducted in subgroups of age, gender, Elixhauser comorbidity index, SOFA quartiles, bacteremic sepsis, and ICU admission. From 2009 to 2015, we identified 55,038 adults with sepsis and assessable BMI measurements: 6% underweight, 33% normal-weight, 28% overweight and 33% obese. Crude mortality was inversely proportional to BMI category: underweight (31%), normal-weight (24%), overweight (19%), obese-class-I (16%), obese-class-II (16%) and obese-class-III (14%). Compared to normal-weight, the adjusted odds ratio [95%CI] of mortality was 1.62[1.50–1.74] for underweight, 0.73[0.70–0.77] for overweight, 0.61[0.57–0.66] for obese-class-I, 0.61[0.55–0.67] for obese-class-II, and 0.65[0.59–0.71] for obese-class-III. Results were consistent in sensitivity analyses. In adults with clinically-defined sepsis, we demonstrate lower short-term mortality in patients with higher BMIs compared to those with normal BMIs (both unadjusted and adjusted analyses) and higher short-term mortality in those with low BMIs. Understanding how obesity improves survival in sepsis would inform prognostic and therapeutic strategies.

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Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity

John T Wilkins, Sadiya S Khan, Donald M. Lloyd-Jones … (2018)

This population-based study calculates lifetime risk estimates for incident cardiovascular disease and subtypes of cardiovascular disease and estimates years lived with and without cardiovascular disease by weight status. Question What is the association of body mass index with cardiovascular disease (CVD) morbidity and mortality? Findings In this population-based study, overweight and obesity were associated with significantly increased risk for CVD. Obesity was associated with shorter longevity and a greater proportion of life lived with CVD; overweight was associated with similar longevity as normal weight but at the expense of a greater proportion of life lived with CVD. Meaning These results provide critical perspective on CVD associated with overweight and obesity and challenge both the obesity paradox as well as the view that overweight is associated with greater longevity. Importance Prior studies have demonstrated lower all-cause mortality in individuals who are overweight compared with those with normal body mass index (BMI), but whether this may come at the cost of greater burden of cardiovascular disease (CVD) is unknown. Objective To calculate lifetime risk estimates of incident CVD and subtypes of CVD and to estimate years lived with and without CVD by weight status. Design, Setting, and Participants In this population-based study, we used pooled individual-level data from adults (baseline age, 20-39, 40-59, and 60-79 years) across 10 large US prospective cohorts, with 3.2 million person-years of follow-up from 1964 to 2015. All participants were free of clinical CVD at baseline with available BMI index and CVD outcomes data. Data were analyzed from October 2016 to July 2017. Exposures World Health Organization–standardized BMI categories. Main Outcomes and Measures Total CVD and CVD subtype, including fatal and nonfatal coronary heart disease, stroke, congestive heart failure, and other CVD deaths. Heights and weights were measured directly by investigators in each study, and BMI was calculated as weight in kilograms divided by height in meters squared. We performed (1) modified Kaplan-Meier analysis to estimate lifetime risks, (2) adjusted competing Cox models to estimate joint cumulative risks for CVD or noncardiovascular death, and (3) the Irwin restricted mean to estimate years lived free of and with CVD. Results Of the 190 672 in-person examinations included in this study, the mean (SD) age was 46.0 (15.0) years for men and 58.7 (12.9) years for women, and 140 835 patients (73.9%) were female. Compared with individuals with a normal BMI (defined as a BMI of 18.5 to 24.9), lifetime risks for incident CVD were higher in middle-aged adults in the overweight and obese groups. Compared with normal weight, among middle-aged men and women, competing hazard ratios for incident CVD were 1.21 (95% CI, 1.14-1.28) and 1.32 (95% CI, 1.24-1.40), respectively, for overweight (BMI, 25.0-29.9), 1.67 (95% CI, 1.55-1.79) and 1.85 (95% CI, 1.72-1.99) for obesity (BMI, 30.0-39.9), and 3.14 (95% CI, 2.48-3.97) and 2.53 (95% CI, 2.20-2.91) for morbid obesity (BMI, ≥40.0). Higher BMI had the strongest association with incident heart failure among CVD subtypes. Average years lived with CVD were longer for middle-aged adults in the overweight and obese groups compared with adults in the normal BMI group. Similar patterns were observed in younger and older adults. Conclusions and Relevance In this study, obesity was associated with shorter longevity and significantly increased risk of cardiovascular morbidity and mortality compared with normal BMI. Despite similar longevity compared with normal BMI, overweight was associated with significantly increased risk of developing CVD at an earlier age, resulting in a greater proportion of life lived with CVD morbidity.

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Body-mass index and mortality among adults with incident type 2 diabetes.

Deirdre Tobias, Wen-An Pan, Chandra Jackson … (2014)

The relation between body weight and mortality among persons with type 2 diabetes remains unresolved, with some studies suggesting decreased mortality among overweight or obese persons as compared with normal-weight persons (an "obesity paradox").

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Predictors of mortality in hospitalized adults with acute exacerbation of chronic obstructive pulmonary disease.

Aran Singanayagam, Stuart Schembri, James Chalmers (2013)

There is a need to identify clinically meaningful predictors of mortality following hospitalized COPD exacerbation. The aim of this study was to systematically review the literature to identify clinically important factors that predict mortality after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD). Eligible studies considered adults admitted to hospital with COPD exacerbation. Two authors independently abstracted data. Odds ratios were then calculated by comparing the prevalence of each predictor in survivors versus nonsurvivors. For continuous variables, mean differences were pooled by the inverse of their variance, using a random effects model. There were 37 studies included (189,772 study subjects) with risk of death ranging from 3.6% for studies considering short-term mortality, 31.0% for long-term mortality (up to 2 yr after hospitalization), and 29.0% for studies that considered solely intensive care unit (ICU)-admitted study subjects. Twelve prognostic factors (age, male sex, low body mass index, cardiac failure, chronic renal failure, confusion, long-term oxygen therapy, lower limb edema, Global Initiative for Chronic Lung Disease criteria stage 4, cor pulmonale, acidemia, and elevated plasma troponin level) were significantly associated with increased short-term mortality. Nine prognostic factors (age, low body mass index, cardiac failure, diabetes mellitus, ischemic heart disease, malignancy, FEV1, long-term oxygen therapy, and PaO2 on admission) were significantly associated with long-term mortality. Three factors (age, low Glasgow Coma Scale score, and pH) were significantly associated with increased risk of mortality in ICU-admitted study subjects. Different factors correlate with mortality from COPD exacerbation in the short term, long term, and after ICU admission. These parameters may be useful to develop tools for prediction of outcome in clinical practice.