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      Association between Class III Obesity (BMI of 40–59 kg/m 2) and Mortality: A Pooled Analysis of 20 Prospective Studies

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      1 , * , 2 , 3 , 1 , 4 , 5 , 6 , 7 , 1 , 8 , 1 , 9 ,   10 , 11 , 12 , 13 , 3 , 10 , 14 , 15 , 16 , 1 , 17 , 1 , 18 , 16 , 19 , 6 , 7 , 20 , 21 , 2 , 3 , 22 , 1 , 1 , 18 , 1 , 1 , 16 , 23 , 24 , 25 , 20 , 22 , 1
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          Abstract

          In a pooled analysis of 20 prospective studies, Cari Kitahara and colleagues find that class III obesity (BMI of 40–59) is associated with excess rates of total mortality, particularly due to heart disease, cancer, and diabetes.

          Please see later in the article for the Editors' Summary

          Abstract

          Background

          The prevalence of class III obesity (body mass index [BMI]≥40 kg/m 2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.

          Methods and Findings

          In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19–83 y at baseline, classified as obese class III (BMI 40.0–59.9 kg/m 2) compared with those classified as normal weight (BMI 18.5–24.9 kg/m 2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976–2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40–44.9, 45–49.9, 50–54.9, and 55–59.9 kg/m 2 was associated with an estimated 6.5 (95% CI: 5.7–7.3), 8.9 (95% CI: 7.4–10.4), 9.8 (95% CI: 7.4–12.2), and 13.7 (95% CI: 10.5–16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report.

          Conclusions

          Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight.

          Please see later in the article for the Editors' Summary

          Editors' Summary

          Background

          The number of obese people (individuals with an excessive amount of body fat) is increasing rapidly in many countries. Worldwide, according to the Global Burden of Disease Study 2013, more than a third of all adults are now overweight or obese. Obesity is defined as having a body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) of more than 30 kg/m 2 (a 183-cm [6-ft] tall man who weighs more than 100 kg [221 lbs] is obese). Compared to people with a healthy weight (a BMI between 18.5 and 24.9 kg/m 2), overweight and obese individuals (who have a BMI between 25.0 and 29.9 kg/m 2 and a BMI of 30 kg/m 2 or more, respectively) have an increased risk of developing diabetes, heart disease, stroke, and some cancers, and tend to die younger. Because people become unhealthily fat by consuming food and drink that contains more energy (kilocalories) than they need for their daily activities, obesity can be prevented or treated by eating less food and by increasing physical activity.

          Why Was This Study Done?

          Class III obesity (extreme, or morbid, obesity), which is defined as a BMI of more than 40 kg/m 2, is emerging as a major public health problem in several high-income countries. In the US, for example, 6% of adults are now morbidly obese. Because extreme obesity used to be relatively uncommon, little is known about the burden of disease, including total and cause-specific mortality (death) rates, among individuals with class III obesity. Before we can prevent and treat class III obesity effectively, we need a better understanding of the health risks associated with this condition. In this pooled analysis of prospective cohort studies, the researchers evaluate the risk of total and cause-specific death and the years of life lost associated with class III obesity. A pooled analysis analyzes the data from several studies as if the data came from one large study; prospective cohort studies record the characteristics of a group of participants at baseline and follow them to see which individuals develop a specific condition.

          What Did the Researchers Do and Find?

          The researchers included 20 prospective (mainly US) cohort studies from the National Cancer Institute Cohort Consortium (a partnership that studies cancer by undertaking large-scale collaborations) in their pooled analysis. After excluding individuals who had ever smoked and people with a history of chronic disease, the analysis included 9,564 adults who were classified as class III obese based on self-reported height and weight at baseline and 304,011 normal-weight adults. Among the participants with class III obesity, mortality rates (deaths per 100,000 persons per year) during the 30-year study period were 856.0 and 663.0 in men and women, respectively, whereas the mortality rates among normal-weight men and women were 346.7 and 280.5, respectively. Heart disease was the major contributor to the excess death rate among individuals with class III obesity, followed by cancer and diabetes. Statistical analyses of the pooled data indicate that the risk of all-cause death and death due to heart disease, cancer, diabetes, and several other diseases increased with increasing BMI. Finally, compared with having a normal weight, having a BMI between 40 and 59 kg/m 2 resulted in an estimated loss of 6.5 to 13.7 years of life.

          What Do These Findings Mean?

          These findings indicate that class III obesity is associated with a substantially increased rate of death. Notably, this death rate increase is similar to the increase associated with smoking among normal-weight people. The findings also suggest that heart disease, cancer, and diabetes are responsible for most of the excess deaths among people with class III obesity and that having class III obesity results in major reductions in life expectancy. Importantly, the number of years of life lost continues to increase for BMI values above 50 kg/m 2, and beyond this point, the loss of life expectancy exceeds that associated with smoking among normal-weight people. The accuracy of these findings is limited by the use of self-reported height and weight measurements to calculate BMI and by the use of BMI as the sole measure of obesity. Moreover, these findings may not be generalizable to all populations. Nevertheless, these findings highlight the need to develop more effective interventions to combat the growing public health problem of class III obesity.

          Additional Information

          Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001673.

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          Most cited references44

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          Beyond body mass index.

          Body mass index (BMI) is the cornerstone of the current classification system for obesity and its advantages are widely exploited across disciplines ranging from international surveillance to individual patient assessment. However, like all anthropometric measurements, it is only a surrogate measure of body fatness. Obesity is defined as an excess accumulation of body fat, and it is the amount of this excess fat that correlates with ill-health. We propose therefore that much greater attention should be paid to the development of databases and standards based on the direct measurement of body fat in populations, rather than on surrogate measures. In support of this argument we illustrate a wide range of conditions in which surrogate anthropometric measures (especially BMI) provide misleading information about body fat content. These include: infancy and childhood; ageing; racial differences; athletes; military and civil forces personnel; weight loss with and without exercise; physical training; and special clinical circumstances. We argue that BMI continues to serve well for many purposes, but that the time is now right to initiate a gradual evolution beyond BMI towards standards based on actual measurements of body fat mass.
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            Morbid obesity rates continue to rise rapidly in the United States.

            Clinically severe or morbid obesity (body mass index (BMI) >40 or 50 kg m(-2)) entails far more serious health consequences than moderate obesity for patients, and creates additional challenges for providers. The paper provides time trends for extreme weight categories (BMI >40 and >50 kg m(-2)) until 2010, using data from the Behavioral Risk Factor Surveillance System. Between 2000 and 2010, the prevalence of a BMI >40 kg m(-2) (type III obesity), calculated from self-reported height and weight, increased by 70%, whereas the prevalence of BMI >50 kg m(-2) increased even faster. Although the BMI rates at every point in time are higher among Hispanics and Blacks, there were no significant differences in trends between them and non-Hispanic Whites. The growth rate appears to have slowed down since 2005. Adjusting for self-report biases, we estimate that in 2010 15.5 million adult Americans or 6.6% of the population had an actual BMI >40 kg m(-2). The prevalence of clinically severe obesity continues to be increasing, although less rapidly in more recent years than prior to 2005.
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              The Agricultural Health Study.

              The Agricultural Health Study, a large prospective cohort study has been initiated in North Carolina and Iowa. The objectives of this study are to: 1) identify and quantify cancer risks among men, women, whites, and minorities associated with direct exposure to pesticides and other agricultural agents; 2) evaluate noncancer health risks including neurotoxicity reproductive effects, immunologic effects, nonmalignant respiratory disease, kidney disease, and growth and development among children; 3) evaluate disease risks among spouses and children of farmers that may arise from direct contact with pesticides and agricultural chemicals used in the home lawns and gardens, and from indirect contact, such as spray drift, laundering work clothes, or contaminated food or water; 4) assess current and past occupational and nonoccupational agricultural exposures using periodic interviews and environmental and biologic monitoring; 5) study the relationship between agricultural exposures, biomarkers of exposure, biologic effect, and genetic susceptibility factors relevant to carcinogenesis; and 6) identify and quantify cancer and other disease risks associated with lifestyle factors such as diet, cooking practices, physical activity, smoking and alcohol consumption, and hair dye use. In the first year of a 3-year enrollment period, 26,235 people have been enrolled in the study, including 19,776 registered pesticide applicators and 6,459 spouses of registered farmer applicators. It is estimated that when the total cohort is assembled in 1997 it will include approximately 75,000 adult study subjects. Farmers, the largest group of registered pesticide applicators comprise 77% of the target population enrolled in the study. This experience compares favorably with enrollment rates of previous prospective studies. Images Figure 1. Figure 2. Figure 3. Figure 4.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                PLoS
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, USA )
                1549-1277
                1549-1676
                July 2014
                8 July 2014
                : 11
                : 7
                : e1001673
                Affiliations
                [1 ]Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
                [2 ]Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America
                [3 ]Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
                [4 ]Division of Cancer Etiology, Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, California, United States of America
                [5 ]Westat, Rockville, Maryland, United States of America
                [6 ]Cancer Epidemiology Centre, Cancer Council of Victoria, Melbourne, Australia
                [7 ]Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, University of Melbourne, Melbourne, Australia
                [8 ]Department of Epidemiology and Biostatistics, School of Public Health and Health Services, George Washington University, Washington, District of Columbia, United States of America
                [9 ]Center for Health Research, School of Public Health, Loma Linda University, Loma Linda, California, United States of America
                [10 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [11 ]Department of Community Medicine, Faculty of Health Sciences, University of Tromsø—The Arctic University of Norway, Tromsø, Norway
                [12 ]Department of Research, Cancer Registry of Norway, Oslo, Norway
                [13 ]Samfundet Folkhälsan, Helsinki, Finland
                [14 ]Department of Epidemiology, School of Medicine, University of California, Irvine, California, United States of America
                [15 ]Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, Maryland, United States of America
                [16 ]Divisions of Preventive Medicine and Aging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
                [17 ]Department of Epidemiology, Biostatistics, and Population Medicine, Loma Linda University School of Public Health, Loma Linda, California, United States of America
                [18 ]Epidemiology Research Program, American Cancer Society, Atlanta, Georgia, United States of America
                [19 ]Massachusetts Veteran's Epidemiology, Research and Information Center, Geriatric Research Education and Clinical Center, VA Boston Healthcare System, Boston, Massachusetts, United States of America
                [20 ]Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
                [21 ]Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, United States of America
                [22 ]Division of Epidemiology, Department of Population Health and NYU Cancer Institute, NYU School of Medicine, New York, New York, United States of America
                [23 ]Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, United States of America
                [24 ]Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [25 ]Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
                University of Cambridge, United Kingdom
                Author notes

                HOA is a member of the Editorial Board of PLOS Medicine. The authors have declared that no other competing interests exist.

                Conceived and designed the experiments: CMK AJF ABdeG SCM PSR PH. Analyzed the data: CMK. Wrote the first draft of the manuscript: CMK AJF ABdeG PH. Contributed to the writing of the manuscript: CMK AJF ABdeG LB MB RJM SCM KR PSR PNS EW HOA HAC RBB JEB DMF GEF LEBF SMG JMG GGG NH JAH FBH KK MSL YP AVP MPP CS HDS KV EW AW AZJ PH. ICMJE criteria for authorship read and met: CMK AJF ABdeG LB MB RJM SCM KR PSR PNS EW HOA HAC RBB JEB DMF GEF LEBF SMG JMG GGG NH JAH FBH KK MSL YP AVP MPP CS HDS KV EW AW AZJ PH. Agree with manuscript results and conclusions: CMK AJF ABdeG LB MB RJM SCM KR PSR PNS EW HOA HAC RBB JEB DMF GEF LEBF SMG JMG GGG NH JAH FBH KK MSL YP AVP MPP CS HDS KV EW AW AZJ PH. Contributed data: AJF LB RJM SCM KR PNS EW HOA HAC JEB DMF GEF LEBF SMG JMG GGG NH JAH FBH KK MSL YP AVP MPP CS HDS KV EW AW AZJ. Harmonized the dataset: MB.

                Article
                PMEDICINE-D-13-04080
                10.1371/journal.pmed.1001673
                4087039
                25003901
                b596b812-ca28-4d47-b7fa-8f67475a3c61
                Copyright @ 2014

                This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 27 December 2013
                : 28 May 2014
                Page count
                Pages: 14
                Funding
                This work was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. Certain data were provided by the Vital Statistics Administration, Maryland Department of Health and Mental Hygiene, Baltimore, Maryland. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Nutrition
                Medicine and Health Sciences
                Epidemiology
                Cancer Epidemiology
                Cardiovascular Disease Epidemiology
                Public and Occupational Health

                Medicine
                Medicine

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