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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.

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.

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    Source

    Lancet (London, England) 383:9921 2014 Mar 15 pg 970-83

    MeSH

    Biomarkers
    Blood Glucose
    Blood Pressure
    Body Mass Index
    Cholesterol
    Coronary Disease
    Humans
    Obesity
    Overweight
    Risk Factors
    Stroke

    Pub Type(s)

    Journal Article
    Meta-Analysis
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24269108

    Citation

    Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects), et al. "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." Lancet (London, England), vol. 383, no. 9921, 2014, pp. 970-83.
    Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects), Lu Y, Hajifathalian K, et al. 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. Lancet. 2014;383(9921):970-83.
    Lu, Y., Hajifathalian, K., Ezzati, M., Woodward, M., Rimm, E. B., & Danaei, G. (2014). 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. Lancet (London, England), 383(9921), pp. 970-83. doi:10.1016/S0140-6736(13)61836-X.
    Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (BMI Mediated Effects), et al. 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. Lancet. 2014 Mar 15;383(9921):970-83. PubMed PMID: 24269108.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - ,, AU - Lu,Yuan, AU - Hajifathalian,Kaveh, AU - Ezzati,Majid, AU - Woodward,Mark, AU - Rimm,Eric B, AU - Danaei,Goodarz, Y1 - 2013/11/22/ PY - 2013/11/26/entrez PY - 2013/11/26/pubmed PY - 2014/3/29/medline SP - 970 EP - 83 JF - Lancet (London, England) JO - Lancet VL - 383 IS - 9921 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/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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/24269108/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(13)61836-X DB - PRIME DP - Unbound Medicine ER -