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A Meta-analysis of 21 Cohort Studies Including More Than 300 000 Persons

Rik P. Bogers, PhD; Wanda J. E. Bemelmans, PhD; Rudolf T. Hoogenveen, MSc; Hendriek C. Boshuizen, PhD; Mark Woodward, PhD; Paul Knekt, PhD; Rob M. van Dam, PhD; Frank B. Hu, MD, PhD; Tommy L. S. Visscher, PhD; Alessandro Menotti, MD, PhD; Roland J. Thorpe Jr, PhD; Konrad Jamrozik, DPhil; Susanna Calling, MD, PhD; Bjørn Heine Strand, PhD; Martin J. Shipley, MSc; for the BMI-CHD Collaboration Investigators

Arch Intern Med. 2007;167(16):1720-1728.

Background  The extent to which moderate overweight (body mass index [BMI], 25.0-29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI,  30.0) are associated with increased risk of coronary heart disease (CHD) through adverse effects on blood pressure and cholesterol levels is unclear, as is the risk of CHD that remains after these mediating effects are considered.

Methods  Relative risks (RRs) of CHD associated with moderate overweight and obesity with and without adjustment for blood pressure and cholesterol concentrations were calculated by the members of a collaboration of prospective cohort studies of healthy, mainly white persons and pooled by means of random-effects models (RRs for categories of BMI in 14 cohorts and for continuous BMI in 21 cohorts; total N = 302 296).

Results  A total of 18 000 CHD events occurred during follow-up. The age-, sex-, physical activity–, and smoking-adjusted RRs (95% confidence intervals) for moderate overweight and obesity compared with normal weight were 1.32 (1.24-1.40) and 1.81 (1.56-2.10), respectively. Additional adjustment for blood pressure and cholesterol levels reduced the RR to 1.17 (1.11-1.23) for moderate overweight and to 1.49 (1.32-1.67) for obesity. The RR associated with a 5-unit BMI increment was 1.29 (1.22-1.35) before and 1.16 (1.11-1.21) after adjustment for blood pressure and cholesterol levels.

Conclusions  Adverse effects of overweight on blood pressure and cholesterol levels could account for about 45% of the increased risk of CHD. Even for moderate overweight, there is a significant increased risk of CHD independent of these traditional risk factors, although confounding (eg, by dietary factors) cannot be completely ruled out.

Author Affiliations: Centre for Prevention and Health Services Research (Drs Bogers, Bemelmans, and Visscher and Mr Hoogenveen) and Expertise Centre for Methodology and Information Services (Dr Boshuizen), National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Epidemiology and Biostatistics Division, The George Institute, Sydney, Australia (Dr Woodward); Department of Health and Functional Capacity, National Public Health Institute, Helsinki, Finland (Dr Knekt); Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts (Drs van Dam and Hu); Institute for Health Sciences, Faculty of Earth and Life Sciences, Vrije Universiteit, Amsterdam, the Netherlands (Drs van Dam and Visscher); Association for Cardiac Research, Rome, Italy (Dr Menotti); Division of Geriatric Medicine and Gerontology, Center on Aging and Health, and the Center for Health Disparities Solutions, The Johns Hopkins Medical Institutions, Baltimore, Maryland (Dr Thorpe); School of Population Health, University of Queensland, Herston, Australia (Dr Jamrozik); Department of Clinical Sciences in Malmö, Epidemiological Research Group, Lund University, Malmö University Hospital, Malmö, Sweden (Dr Calling); Division of Epidemiology, Norwegian Institute of Public Health, Oslo (Dr Strand); and Department of Epidemiology and Public Health, University College London, London, England (Mr Shipley).

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