Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2014 Mar 15;383(9921):970-83.
doi: 10.1016/S0140-6736(13)61836-X. Epub 2013 Nov 22.

Metabolic Mediators of the Effects of Body-Mass Index, Overweight, and Obesity on Coronary Heart Disease and Stroke: A Pooled Analysis of 97 Prospective Cohorts With 1·8 Million Participants

Collaborators
Free PMC article
Meta-Analysis

Metabolic Mediators of the Effects of Body-Mass Index, Overweight, and Obesity on Coronary Heart Disease and Stroke: A Pooled Analysis of 97 Prospective Cohorts With 1·8 Million Participants

Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects) et al. Lancet. .
Free PMC article

Abstract

Background: Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors.

Methods: We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57,161 coronary heart disease and 31,093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m(2), or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators.

Findings: The HR for each 5 kg/m(2) higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m(2)) and obesity (BMI ≥30 kg/m(2)) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m(2)), with 50% (44-58) of the excess risk of overweight and 44% (41-48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69-155) for overweight and 69% (64-77) for obesity.

Interpretation: Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits.

Funding: US National Institute of Health, UK Medical Research Council, National Institute for Health Research Comprehensive Biomedical Research Centre at Imperial College Healthcare NHS Trust, Lown Scholars in Residence Program on cardiovascular disease prevention, and Harvard Global Health Institute Doctoral Research Grant.

Figures

Figure 1
Figure 1
Hazard ratios per 5 kg/m2 higher body-mass index adjusted for different combinations of mediators in coronary heart disease and stroke All hazard ratios were also adjusted for confounders as described in Methods. The appendix (pp 19–36) shows cohort-specific hazard ratios.
Figure 2
Figure 2
Stratified analyses of HRs per 5 kg/m2 higher body-mass index, with and without adjustment for mediators in CHD (A) and stroke (B) p values were meta-regression p values between groups. Results are presented for all three mediators combined. The appendix (pp 73–90) shows HRs with adjustment for combinations of one and two mediators. CHD=coronary heart disease. HR=hazard ratio
Figure 3
Figure 3
Percentage of excess risk per 5 kg/m2 higher body-mass index mediated through different combinations of metabolic risk factors in coronary heart disease and stroke

Comment in

Similar articles

See all similar articles

Cited by 237 articles

See all "Cited by" articles

References

    1. Lozano R, Naghavi M, Foreman K. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2095–2128. - PubMed
    1. Whitlock G, Lewington S, Sherliker P, the Prospective Studies Collaboration Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083–1096. - PMC - PubMed
    1. Wormser D, Kaptoge S, Di Angelantonio E, the Emerging Risk Factors Collaboration Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet. 2011;377:1085–1095. - PMC - PubMed
    1. Singh GM, Danaei G, Farzadfar F, the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group. Asia-Pacific Cohort Studies Collaboration (APCSC) the Diabetes Epidemiology: Collaborative analysis of Diagnostic criteria in Europe (DECODE) the Emerging Risk Factor Collaboration (ERFC) the Prospective Studies Collaboration (PSC) The age-specific quantitative effects of metabolic risk factors on cardiovascular diseases and diabetes: a pooled analysis. PLoS One. 2013;8:e65174. - PMC - PubMed
    1. Poirier P, Giles TD, Bray GA, the American Heart Association. the Obesity Committee of the Council on Nutrition. Physical Activity, and Metabolism Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898–918. - PubMed

Publication types

Feedback