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

doi:10.1016/S0140-6736(11)60105-0

Meta-Analysis

. 2011 Mar 26;377(9771):1085-95.

doi: 10.1016/S0140-6736(11)60105-0.

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

Collaborators, Affiliations

Collaborators

Emerging Risk Factors Collaboration:
A R Folsom, L 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 Sr, R S Vasan, C S Fox, M J Pencina, 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 Ärnlöv, 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

Affiliation

¹ Emerging Risk Factors Collaboration Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK. erfc@phpc.cam.ac.uk

PMID: 21397319
PMCID: PMC3145074
DOI: 10.1016/S0140-6736(11)60105-0

Meta-Analysis

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

Emerging Risk Factors Collaboration et al. Lancet. 2011.

. 2011 Mar 26;377(9771):1085-95.

doi: 10.1016/S0140-6736(11)60105-0.

Collaborators

Emerging Risk Factors Collaboration:
A R Folsom, L 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 Sr, R S Vasan, C S Fox, M J Pencina, 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 Ärnlöv, 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

Affiliation

¹ Emerging Risk Factors Collaboration Coordinating Centre, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK. erfc@phpc.cam.ac.uk

PMID: 21397319
PMCID: PMC3145074
DOI: 10.1016/S0140-6736(11)60105-0

Abstract

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/m(2) 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/m(2) 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.

Funding: British Heart Foundation and UK Medical Research Council.

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Figures

**Figure 1**
HRs for coronary heart disease and ischaemic stroke across quantiles of baseline BMI, waist circumference, and waist-to-hip ratio Regression analyses were stratified, where appropriate, by sex. Adjusted study-specific log HRs were combined by multivariate random-effects meta-analysis. Y-axes are shown on a log scale. Reference groups are the second deciles in the plots for coronary heart disease and the first quintiles in the plots for ischaemic stroke. HR=hazard ratio. BMI=body-mass index. *Intermediate risk factors were systolic blood pressure, history of diabetes, and total and HDL cholesterol.

**Figure 2**
HRs for coronary heart disease (A) and ischaemic stroke (B) per 1 SD higher baseline values of BMI, waist circumference, and waist-to-hip ratio, according to age, sex, and BMI at baseline Analyses for coronary heart disease were based on up to 203 338 participants from 51 studies, and analyses for ischaemic stroke were based on up to 122 914 participants from 25 studies. HRs are presented per 4·56 kg/m² higher BMI, 12·6 cm higher waist circumference, and 0·083 higher waist-to-hip ratio (ie, 1 SD higher baseline values). Study-specific HRs were adjusted for age at baseline and smoking status, and stratified, where appropriate, by sex. Analyses were restricted to participants with BMI of 20 kg/m² or higher. X-axes are shown on a log scale. p values for interaction were calculated by use of continuous values of variables, when appropriate. HRs for coronary heart disease, initially adjusted for age, sex, and smoking status, and then additionally adjusted for BMI, were 1·31 (1·24–1·37) and 1·23 (1·15–1·32), respectively, with waist circumference, and 1·29 (1·23–1·35) and 1·21 (1·16–1·26), respectively, with waist-to-hip ratio. HRs for ischaemic stroke, initially adjusted for age, sex, and smoking status, and then additionally adjusted for BMI, were 1·26 (1·19–1·33) and 1·26 (1·16–1·36), respectively, with waist circumference, and 1·25 (1·19–1·32) and 1·18 (1·13–1·24), respectively, with waist-to-hip ratio. BMI=body-mass index. HR=hazard ratio.

**Figure 3**
HRs for coronary heart disease across thirds of waist circumference (A) and waist-to-hip ratio (B) by baseline values of BMI Analyses were based on 203 338 participants (7750 cases) from 51 studies. Analyses were restricted to participants with BMI of 20 kg/m² or higher. Regression analyses were adjusted for age at baseline and smoking status, and stratified, where appropriate, by sex. Adjusted study-specific log HRs were combined by multivariate random-effects meta-analysis. Y-axes are shown on a log scale. Reference groups are the lowest third of waist circumference or waist-to-hip ratio in the bottom third of BMI. Results were similar for the full BMI range. BMI=body-mass index. HR=hazard ratio.

**Figure 4**
Changes in C-index for cardiovascular disease risk prediction from addition of adiposity measures or conventional risk factors to a model containing age and sex only Analyses were based on 144 795 participants (8347 cardiovascular events) in 39 studies. Analyses were restricted to participants with BMI of 20 kg/m² or higher. BMI=body-mass index. *Reference C-index was 0·6741 (95% CI 0·6685 to 0·6798) for the model including age and stratified by sex. †p=0·0001 for change in C-index after addition of waist circumference into the model with age, sex, and BMI. ‡p<0·0001 for change in C-index after addition of waist-to-hip ratio into the model with age, sex, and BMI. §Smoking status, systolic blood pressure, and history of diabetes. ¶Smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol.

**Figure 5**
Changes in C-index for cardiovascular disease risk prediction from addition of adiposity measures or lipid markers to a non-lipid-based model Analyses were based on 144 795 participants (8347 cardiovascular events) in 39 studies. Analyses were restricted to participants with BMI of 20 kg/m² or higher. BMI=body-mass index. *Reference C-index was 0·7238 (95% CI 0·7186 to 0·7291) for the model including age, smoking status, systolic blood pressure, and history of diabetes, and stratified by sex. †p=0·175 for change in C-index after addition of waist circumference into the reference model plus BMI. ‡p<0·0001 for change in C-index after addition of waist-to-hip ratio into the reference model plus BMI.

**Figure 6**
Changes in C-index for cardiovascular disease risk prediction from omission of individual risk factors from a full model containing Framingham risk score covariates plus BMI, waist circumference, or waist-to-hip ratio Analyses were based on 144 795 participants (8347 cardiovascular events) in 39 studies. Analyses were restricted to participants with BMI of 20 kg/m² or higher. BMI=body-mass index. *Framingham risk score covariates include age, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol, and model was stratified by sex. †Reference C-index of 0·7324 (95% CI 0·7272 to 0·7375). ‡Reference C-index of 0·7324 (95% CI 0·7273 to 0·7376). §Reference C-index of 0·7333 (95% CI 0·7281 to 0·7384).

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Comment in

Size still matters…but not in the way we once thought.
Huxley RR, Jacobs DR Jr. Huxley RR, et al. Lancet. 2011 Mar 26;377(9771):1051-2. doi: 10.1016/S0140-6736(11)60239-0. Lancet. 2011. PMID: 21397321 No abstract available.
Risk factors: little need to incorporate obesity measures in calculations of cardiovascular disease risk.
Mearns BM. Mearns BM. Nat Rev Cardiol. 2011 May;8(5):241. doi: 10.1038/nrcardio.2011.52. Epub 2011 Mar 29. Nat Rev Cardiol. 2011. PMID: 21451470 No abstract available.
Cardiovascular endocrinology: Cardiovascular risk-general versus abdominal adiposity.
Koch L. Koch L. Nat Rev Endocrinol. 2011 Jun;7(6):312. doi: 10.1038/nrendo.2011.62. Epub 2011 Apr 12. Nat Rev Endocrinol. 2011. PMID: 21487431 No abstract available.
Body-mass index, abdominal adiposity, and cardiovascular risk.
Yusuf S, Anand S. Yusuf S, et al. Lancet. 2011 Jul 16;378(9787):226-7; author reply 228. doi: 10.1016/S0140-6736(11)61120-3. Lancet. 2011. PMID: 21763930 No abstract available.
Body-mass index, abdominal adiposity, and cardiovascular risk.
Gonçalves FB, Koek M, Verhagen HJ, Niessen WJ, Poldermans D. Gonçalves FB, et al. Lancet. 2011 Jul 16;378(9787):227; author reply 228. doi: 10.1016/S0140-6736(11)61121-5. Lancet. 2011. PMID: 21763933 No abstract available.

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References

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1. Yusuf S, Hawken S, Ôunpuu S, on behalf of the INTERHEART Study Investigators Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study. Lancet. 2005;366:1640–1649. - PubMed

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[1] Ferket BS, Colkesen EB, Visser JJ. Systematic review of guidelines on cardiovascular risk assessment: which recommendations should clinicians follow for a cardiovascular health check? Arch Intern Med. 2010;170:27–40. - PubMed

[2] Ferket BS, Colkesen EB, Visser JJ. Systematic review of guidelines on cardiovascular risk assessment: which recommendations should clinicians follow for a cardiovascular health check? Arch Intern Med. 2010;170:27–40. - PubMed

[3] WHO Consultation of Obesity . Obesity: preventing and managing the global epidemic. World Health Organization; Geneva, Switzerland: 2000. - PubMed

[4] WHO Consultation of Obesity . Obesity: preventing and managing the global epidemic. World Health Organization; Geneva, Switzerland: 2000. - PubMed

[5] National Institutes of Health Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes Res. 1998;6(suppl 2):51S–209S. - PubMed

[6] National Institutes of Health Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes Res. 1998;6(suppl 2):51S–209S. - PubMed

[7] Cooney MT, Dudina AL, Graham IM. Value and limitations of existing scores for the assessment of cardiovascular risk: a review for clinicians. J Am Coll Cardiol. 2009;54:1209–1227. - PubMed

[8] Cooney MT, Dudina AL, Graham IM. Value and limitations of existing scores for the assessment of cardiovascular risk: a review for clinicians. J Am Coll Cardiol. 2009;54:1209–1227. - PubMed

[9] Yusuf S, Hawken S, Ôunpuu S, on behalf of the INTERHEART Study Investigators Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study. Lancet. 2005;366:1640–1649. - PubMed

[10] Yusuf S, Hawken S, Ôunpuu S, on behalf of the INTERHEART Study Investigators Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study. Lancet. 2005;366:1640–1649. - PubMed

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

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

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