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

The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects)

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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/m2, 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/m2 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/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), 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.

Original languageEnglish
Pages (from-to)970-983
Number of pages14
JournalThe Lancet
Volume383
Issue number9921
DOIs
Publication statusPublished - 2014 Jan 1

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Coronary Disease
Body Mass Index
Obesity
Stroke
Cholesterol
Blood Pressure
Blood Glucose
Risk Adjustment
Western Australia
North America
New Zealand
Cohort Studies
Maintenance
Prospective Studies
Hypertension
Weights and Measures

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects). / 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. In: The Lancet. 2014 ; Vol. 383, No. 9921. pp. 970-983.
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title = "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",
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/m2, 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/m2 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/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), 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.",
author = "{The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects)} and Yuan Lu and Kaveh Hajifathalian and Majid Ezzati and Mark Woodward and Rimm, {Eric B.} and Goodarz Danaei and Randi Selmer and Strand, {Bjorn H.} and A. Dobson and A. Hozawa and A. Nozaki and Akira Okayama and A. Rodgers and A. Tamakoshi and Zhou, {B. F.} and B. Zhou and Yao, {C. H.} and Jiang, {C. Q.} and Gu, {D. F.} and D. Heng and Giles, {Graham G.} and Shan, {G. L.} and G. Whitlock and H. Arima and Kim, {H. C.} and H. Christensen and H. Horibe and H. Maegawa and H. Tanaka and Hirotsugu Ueshima and Zhang, {H. Y.} and Kim, {I. S.} and I. Suh and Fuh, {J. L.} and J. Lee and Jean Woo and Xie, {J. X.} and J. Zhou and K. Hughes and K. Jamrozik and K. Nakachi and K. Sakata and K. Shimamoto and Chen, {L. Q.} and Liu, {L. S.} and M. Hobbs and M. Iida and M. Kagaya and Divitini, {Mark L.} and M. Luszcz",
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language = "English",
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pages = "970--983",
journal = "The Lancet",
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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. / The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects).

In: The Lancet, Vol. 383, No. 9921, 01.01.2014, p. 970-983.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke

T2 - A pooled analysis of 97 prospective cohorts with 1·8 million participants

AU - The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects)

AU - Lu, Yuan

AU - Hajifathalian, Kaveh

AU - Ezzati, Majid

AU - Woodward, Mark

AU - Rimm, Eric B.

AU - Danaei, Goodarz

AU - Selmer, Randi

AU - Strand, Bjorn H.

AU - Dobson, A.

AU - Hozawa, A.

AU - Nozaki, A.

AU - Okayama, Akira

AU - Rodgers, A.

AU - Tamakoshi, A.

AU - Zhou, B. F.

AU - Zhou, B.

AU - Yao, C. H.

AU - Jiang, C. Q.

AU - Gu, D. F.

AU - Heng, D.

AU - Giles, Graham G.

AU - Shan, G. L.

AU - Whitlock, G.

AU - Arima, H.

AU - Kim, H. C.

AU - Christensen, H.

AU - Horibe, H.

AU - Maegawa, H.

AU - Tanaka, H.

AU - Ueshima, Hirotsugu

AU - Zhang, H. Y.

AU - Kim, I. S.

AU - Suh, I.

AU - Fuh, J. L.

AU - Lee, J.

AU - Woo, Jean

AU - Xie, J. X.

AU - Zhou, J.

AU - Hughes, K.

AU - Jamrozik, K.

AU - Nakachi, K.

AU - Sakata, K.

AU - Shimamoto, K.

AU - Chen, L. Q.

AU - Liu, L. S.

AU - Hobbs, M.

AU - Iida, M.

AU - Kagaya, M.

AU - Divitini, Mark L.

AU - Luszcz, M.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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/m2, 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/m2 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/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), 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.

AB - 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/m2, 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/m2 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/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), 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.

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JO - The Lancet

JF - The Lancet

SN - 0140-6736

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