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      Central fatness and risk of all cause mortality: systematic review and dose-response meta-analysis of 72 prospective cohort studies

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          Abstract

          Objective

          To quantify the association of indices of central obesity, including waist circumference, hip circumference, thigh circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, and A body shape index, with the risk of all cause mortality in the general population, and to clarify the shape of the dose-response relations.

          Design

          Systematic review and meta-analysis.

          Data sources

          PubMed and Scopus from inception to July 2019, and the reference lists of all related articles and reviews.

          Eligibility criteria for selecting studies

          Prospective cohort studies reporting the risk estimates of all cause mortality across at least three categories of indices of central fatness. Studies that reported continuous estimation of the associations were also included.

          Data synthesis

          A random effects dose-response meta-analysis was conducted to assess linear trend estimations. A one stage linear mixed effects meta-analysis was used for estimating dose-response curves.

          Results

          Of 98 745 studies screened, 1950 full texts were fully reviewed for eligibility. The final analyses consisted of 72 prospective cohort studies with 2 528 297 participants. The summary hazard ratios were as follows: waist circumference (10 cm, 3.94 inch increase): 1.11 (95% confidence interval 1.08 to 1.13, I 2=88%, n=50); hip circumference (10 cm, 3.94 inch increase): 0.90 (0.81 to 0.99, I 2=95%, n=9); thigh circumference (5 cm, 1.97 inch increase): 0.82 (0.75 to 0.89, I 2=54%, n=3); waist-to-hip ratio (0.1 unit increase): 1.20 (1.15 to 1.25, I 2=90%, n=31); waist-to-height ratio (0.1 unit increase): 1.24 (1.12 to 1.36, I 2=94%, n=11); waist-to-thigh ratio (0.1 unit increase): 1.21 (1.03 to 1.39, I 2=97%, n=2); body adiposity index (10% increase): 1.17 (1.00 to 1.33, I 2=75%, n=4); and A body shape index (0.005 unit increase): 1.15 (1.10 to 1.20, I 2=87%, n=9). Positive associations persisted after accounting for body mass index. A nearly J shaped association was found between waist circumference and waist-to-height ratio and the risk of all cause mortality in men and women. A positive monotonic association was observed for waist-to-hip ratio and A body shape index. The association was U shaped for body adiposity index.

          Conclusions

          Indices of central fatness including waist circumference, waist-to-hip ratio, waist-to-height ratio, waist-to-thigh ratio, body adiposity index, and A body shape index, independent of overall adiposity, were positively and significantly associated with a higher all cause mortality risk. Larger hip circumference and thigh circumference were associated with a lower risk. The results suggest that measures of central adiposity could be used with body mass index as a supplementary approach to determine the risk of premature death.

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          Most cited references101

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          Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study.

          Visceral adipose tissue (VAT) compartments may confer increased metabolic risk. The incremental utility of measuring both visceral and subcutaneous abdominal adipose tissue (SAT) in association with metabolic risk factors and underlying heritability has not been well described in a population-based setting. Participants (n=3001) were drawn from the Framingham Heart Study (48% women; mean age, 50 years), were free of clinical cardiovascular disease, and underwent multidetector computed tomography assessment of SAT and VAT volumes between 2002 and 2005. Metabolic risk factors were examined in relation to increments of SAT and VAT after multivariable adjustment. Heritability was calculated using variance-components analysis. Among both women and men, SAT and VAT were significantly associated with blood pressure, fasting plasma glucose, triglycerides, and high-density lipoprotein cholesterol and with increased odds of hypertension, impaired fasting glucose, diabetes mellitus, and metabolic syndrome (P range < 0.01). In women, relations between VAT and risk factors were consistently stronger than in men. However, VAT was more strongly correlated with most metabolic risk factors than was SAT. For example, among women and men, both SAT and VAT were associated with increased odds of metabolic syndrome. In women, the odds ratio (OR) of metabolic syndrome per 1-standard deviation increase in VAT (OR, 4.7) was stronger than that for SAT (OR, 3.0; P for difference between SAT and VAT < 0.0001); similar differences were noted for men (OR for VAT, 4.2; OR for SAT, 2.5). Furthermore, VAT but not SAT contributed significantly to risk factor variation after adjustment for body mass index and waist circumference (P < or = 0.01). Among overweight and obese individuals, the prevalence of hypertension, impaired fasting glucose, and metabolic syndrome increased linearly and significantly across increasing VAT quartiles. Heritability values for SAT and VAT were 57% and 36%, respectively. Although both SAT and VAT are correlated with metabolic risk factors, VAT remains more strongly associated with an adverse metabolic risk profile even after accounting for standard anthropometric indexes. Our findings are consistent with the hypothesized role of visceral fat as a unique, pathogenic fat depot. Measurement of VAT may provide a more complete understanding of metabolic risk associated with variation in fat distribution.
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            A New Body Shape Index Predicts Mortality Hazard Independently of Body Mass Index

            Background Obesity, typically quantified in terms of Body Mass Index (BMI) exceeding threshold values, is considered a leading cause of premature death worldwide. For given body size (BMI), it is recognized that risk is also affected by body shape, particularly as a marker of abdominal fat deposits. Waist circumference (WC) is used as a risk indicator supplementary to BMI, but the high correlation of WC with BMI makes it hard to isolate the added value of WC. Methods and Findings We considered a USA population sample of 14,105 non-pregnant adults ( ) from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 with follow-up for mortality averaging 5 yr (828 deaths). We developed A Body Shape Index (ABSI) based on WC adjusted for height and weight: ABSI had little correlation with height, weight, or BMI. Death rates increased approximately exponentially with above average baseline ABSI (overall regression coefficient of per standard deviation of ABSI [95% confidence interval: – ]), whereas elevated death rates were found for both high and low values of BMI and WC. ( – ) of the population mortality hazard was attributable to high ABSI, compared to ( – ) for BMI and ( – ) for WC. The association of death rate with ABSI held even when adjusted for other known risk factors including smoking, diabetes, blood pressure, and serum cholesterol. ABSI correlation with mortality hazard held across the range of age, sex, and BMI, and for both white and black ethnicities (but not for Mexican ethnicity), and was not weakened by excluding deaths from the first 3 yr of follow-up. Conclusions Body shape, as measured by ABSI, appears to be a substantial risk factor for premature mortality in the general population derivable from basic clinical measurements. ABSI expresses the excess risk from high WC in a convenient form that is complementary to BMI and to other known risk factors.
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              Adiposity and cancer at major anatomical sites: umbrella review of the literature

              Objective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer. Design Umbrella review of systematic reviews and meta-analyses. Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references. Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer. Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m2 increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality. Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.
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                Author and article information

                Contributors
                Role: doctoral student of nutrition
                Role: research fellow
                Role: masters student of nursing
                Role: postdoctoral fellow
                Role: associate professor of nutrition
                Journal
                BMJ
                BMJ
                BMJ-UK
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2020
                23 September 2020
                : 370
                : m3324
                Affiliations
                [1 ]Food Safety Research Center (salt), Semnan University of Medical Sciences, Semnan, Iran
                [2 ]Department of Community Nutrition, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, PO Box 14155/6117, Tehran, Iran
                [3 ]Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
                [4 ]Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
                [5 ]Nursing Care Research Center, Semnan University of Medical Sciences, Semnan, Iran
                [6 ]Clinical Nutrition and Risk Factor Modification Centre, St Michael’s Hospital, Toronto, Ontario, Canada
                [7 ]Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
                [8 ]Toronto 3D Knowledge Synthesis & Clinical Trials Unit, St Michael’s Hospital, Toronto, Ontario, Canada
                Author notes
                Correspondence to: S Shab-Bidar s_shabbidar@ 123456tums.ac.ir
                Author information
                http://orcid.org/0000-0002-0167-7174
                Article
                jaya052590
                10.1136/bmj.m3324
                7509947
                32967840
                7d92014d-c148-4187-864f-a9576b980bfd
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 11 August 2020
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                Research

                Medicine
                Medicine

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