Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: Collaborative analysis of 58 prospective studies

David Wormser, Stephen Kaptoge, Emanuele Di Angelantonio, Angela M. Wood, Lisa Pennells, Alex Thompson, Nadeem Sarwar, Jorge R. Kizer, Debbie A. Lawlor, Børge G. Nordestgaard, Paul Ridker, Veikko Salomaa, June Stevens, Mark Woodward, Naveed Sattar, Rory Collins, Simon G. Thompson, Gary Whitlock, John Danesh, A. R. FolsomL. E. Chambless, J. Stevens, D. B. Panagiotakos, C. Pitsavos, C. Chrysohoou, C. Stefanadis, R. Atkins, E. L.M. Barr, J. E. Shaw, P. Z. Zimmet, P. H. Whincup, S. G. Wannamethee, R. W. Morris, S. Kiechl, J. Willeit, F. Oberhollenzer, A. Mayr, S. Ebrahim, D. A. Lawlor, J. Yarnell, J. Gallacher, P. J. Nietert, S. E. Sutherland, D. L. Bachman, J. E. Keil, K. J. Mukamal, J. R. Kizer, I. H. De Boer, A. Tybjærg-Hansen, B. G. Nordestgaard, R. Frikke-Schmidt, S. Giampaoli, L. Palmieri, S. Panico, D. Vanuzzo, L. Pilotto, A. Gómez De La Cámara, M. A. Rubio, D. G. Blazer, J. M. Guralnik, C. L. Phillips, K. T. Khaw, V. Salomaa, K. Harald, P. Jousilahti, E. Vartiainen, R. B. D’Agostino, R. S. Vasan, C. S. Fox, M. J. Pencina, H. R. Dankner, A. Chetrit, F. Lubin, L. Wilhelmsen, H. Eriksson, K. Svärdsudd, L. Welin, A. Rosengren, L. Wilhelmsen, G. Lappas, H. Eriksson, C. Björkelund, L. Lissner, C. Bengtsson, T. E. Strandberg, V. Salomaa, R. S. Tilvis, T. A. Miettinen, Y. Kiyohara, H. Arima, Y. Doi, T. Ninomiya, J. M. Dekker, G. Nijpels, C. D.A. Stehouwer, E. B. Rimm, J. K. Pai, H. Iso, A. Kitamura, K. Yamagishi, H. Noda, D. Deeg, J. L. Poppelaars, A. R. Folsom, B. M. Psaty, S. Shea, A. Döring, W. Koenig, C. Meisinger, W. M.M. Verschuren, A. Blokstra, H. B. Bueno-De-Mesquita, L. Wilhelmsen, A. Rosengren, G. Lappas, A. Fletcher, R. F. Gillum, M. Mussolino, E. B. Rimm, S. E. Hankinson, J. E. Manson, J. K. Pai, K. W. Davidson, S. Kirkland, J. A. Shaffer, M. R. Korin, A. Kitamura, H. Iso, S. Sato, S. J.L. Bakker, R. T. Gansevoort, H. L. Hillege, P. Amouyel, D. Arveiler, A. Evans, J. Ferrières, E. Barrett-Connor, D. L. Wingard, R. Bettencourt, J. Witteman, I. Kardys, H. Tiemeier, A. Hofman, H. Tunstall-Pedoe, R. Tavendale, G. D.O. Lowe, M. Woodward, B. V. Howard, Y. Zhang, L. Best, J. Umans, A. Onat, G. Hergenç, G. Can, H. Nakagawa, M. Sakurai, K. Nakamura, Y. Morikawa, I. Njølstad, E. B. Mathiesen, M. L. Løchen, T. Wilsgaard, J. ørnlöv, J. Sundström, U. Risérus, E. Ingelsson, S. Wassertheil-Smoller, J. E. Manson, E. Brunner, M. Shipley, P. Ridker, J. Buring, M. Walker, S. Watson, M. Alexander, A. S. Butterworth, R. Collins, E. Di Angelantonio, O. H. Franco, P. Gao, R. Gobin, P. Haycock, S. Kaptoge, S. R. Kondapally Seshasai, S. Lewington, L. Pennells, N. Sarwar, A. Thompson, S. G. Thompson, M. Walker, S. Watson, I. R. White, A. M. Wood, D. Wormser, J. Danesh

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Background Guidelines differ about the value of assessment of adiposity measures for cardiovascular disease risk prediction when information is available for other risk factors. We studied the separate and combined associations of body-mass index (BMI), waist circumference, and waist-to-hip ratio with risk of first-onset cardiovascular disease. Methods We used individual records from 58 cohorts to calculate hazard ratios (HRs) per 1 SD higher baseline values (4·56 kg/m² higher BMI, 12·6 cm higher waist circumference, and 0·083 higher waist-to-hip ratio) and measures of risk discrimination and reclassification. Serial adiposity assessments were used to calculate regression dilution ratios. Results Individual records were available for 221 934 people in 17 countries (14 297 incident cardiovascular disease outcomes; 1·87 million person-years at risk). Serial adiposity assessments were made in up to 63 821 people (mean interval 5·7 years [SD 3·9]). In people with BMI of 20 kg/m² or higher, HRs for cardiovascular disease were 1·23 (95% CI 1·17-1·29) with BMI, 1·27 (1·20-1·33) with waist circumference, and 1·25 (1·19-1·31) with waist-to-hip ratio, after adjustment for age, sex, and smoking status. After further adjustment for baseline systolic blood pressure, history of diabetes, and total and HDL cholesterol, corresponding HRs were 1·07 (1·03-1·11) with BMI, 1·10 (1·05-1·14) with waist circumference, and 1·12 (1·08-1·15) with waist-to-hip ratio. Addition of information on BMI, waist circumference, or waist-to-hip ratio to a cardiovascular disease risk prediction model containing conventional risk factors did not importantly improve risk discrimination (C-index changes of-0·0001,-0·0001, and 0·0008, respectively), nor classification of participants to categories of predicted 10-year risk (net reclassification improvement-0·19%,-0·05%, and-0·05%, respectively). Findings were similar when adiposity measures were considered in combination. Reproducibility was greater for BMI (regression dilution ratio 0·95, 95% CI 0·93-0·97) than for waist circumference (0·86, 0·83-0·89) or waist-to-hip ratio (0·63, 0·57-0·70). Interpretation BMI, waist circumference, and waist-to-hip ratio, whether assessed singly or in combination, do not importantly improve cardiovascular disease risk prediction in people in developed countries when additional information is available for systolic blood pressure, history of diabetes, and lipids.

Original languageEnglish (US)
Pages (from-to)1085-1095
Number of pages11
JournalThe Lancet
Issue number9771
StatePublished - 2011

Bibliographical note

Funding Information:
AT has been a consultant for GlaxoSmithKline, and is now an employee of Roche. JRK and his institution have received research grants from the National Heart, Lung and Blood Institute, and diaDexus; and JRK has received payment for lectures from Merck. DAL's institution has received funding from Department of Health Policy Research Programme and the British Heart Foundation. PR's institution has received research grants from the National Institutes of Health, the National Cancer Institute, AstraZeneca, Novartis, and Merck. PR is listed as a co-inventor on patents relating to the use of inflammatory biomarkers in cardiovascular disease that are held by the Brigham and Women's Hospital and have been licensed to Siemens and AstraZeneca; and has served as a consultant to Genzyme, Vascular Biogenics, Boerringher Ingelheim, and Amylin. NSat's institution has received research grants from Allergan. RC and GW's institution has received research funding from Merck, AstraZeneca, Bristol-Myers Squibb, Schering-Plough, Novartis, Bayer, and Solvay. RC's institution has also received travel and accommodation expenses from Merck. JD has been a board member for Merck and Novartis; and has been a consultant for Novartis, Merck, GlaxoSmithKline, and Pfizer. JD's institution has received research grants from the British Heart Foundation, BUPA Foundation, Denka, diaDexus, European Union, Evelyn Trust, Fogarty International Centre, GlaxoSmithKline, Merck, National Heart, Lung and Blood Institute, National Institute of Neurological Disorders and Stroke, Novartis, Pfizer, Roche, UK Biobank, UK Medical Research Council, and Wellcome Trust. All other members of the writing committee declare that they have no conflicts of interest.

Funding Information:
The Emerging Risk Factors Collaboration Coordinating Centre is underpinned by a programme grant from the British Heart Foundation ( RG/08/014 ) and grants from the UK Medical Research Council. Various sources have supported recruitment, follow-up, and laboratory measurements in the 122 cohorts contributing to the Emerging Risk Factors Collaboration. Investigators of several of these studies have contributed to a list naming some of these funding sources.

Publisher Copyright:
© 2011, Lancet Publishing Group. All rights reserved.


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