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.
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.
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DOI：
10.1016/s0140-6736(13)61836-x
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发表时间：
2014-03-15
期刊：
影响因子：
168.9
通讯作者：
Danaei, Goodarz
中科院分区：
文献类型：
--
作者：
Lu, Yuan;Hajifathalian, Kaveh;Ezzati, Majid;Woodward, Mark;Rimm, Eric B.;Danaei, Goodarz
体重指数(BMI)和糖尿病在全球范围内有所增加，而全球平均血压和胆固醇在过去30年里下降或保持不变。我们量化了BMI对冠心病和中风的影响中有多少是通过血压、胆固醇和血糖来调节的，以及有多少是独立于这些因素的。我们汇集了97项前瞻性队列研究的数据，这些研究在1948年至2005年期间总共招募了180万名参与者，其中包括57例 161例冠心病和31例 093中风事件。对于每个队列，我们排除了年龄在18岁以下、体重指数低于20公斤/平方米、或有冠心病或中风病史的参与者。我们估算了在对所有可能的血压、胆固醇和血糖组合进行调整和不进行调整的情况下，体重指数对冠心病和中风的风险比(HR)。我们用随机效应模型合并了人力资源，并计算了中介调整后的超额风险衰减。校正混杂因素后，BMI每增加5 kg/m2，冠心病的HR为1.27(95%CI为1.23~1.31)，卒中的HR为1.18(1.14~1.22)。对3个代谢危险因素的额外调整使冠心病和卒中的HR分别降至1.15(1.12-1.18)和1.04(1.01-1.08)，提示46%(95%CI 42-50)的冠心病和76%(65-91)的BMI超额危险是由这些因素调节的。血压是最重要的中介因素，占冠心病额外风险的31%(28-35)，中风的65%(56-75)。在亚洲和西方队列(北美、西欧、澳大利亚和新西兰)之间，这三个中介中介的超额风险百分比没有显著差异。超重(BMI≥25~30 kg/m2)和肥胖(BMI≥30 kg/m2)与正常体重(BMI≥20~25 kg/m2)相比，冠心病和中风的风险显著增加，其中50%(44-58)的超重风险(44-58)和44%(41-48)的肥胖风险(41-48)由所选的三个中介因素调节。卒中的超重比例为98%(69-155)，肥胖比例为69%(-77)。降低高血压、胆固醇和血糖的干预措施可能会解决与高BMI相关的大约一半的冠心病额外风险和四分之三的中风额外风险。为了充分受益，需要保持最佳的体重。美国国立卫生研究院、英国医学研究理事会、帝国理工学院NHS信托基金的国家卫生研究所综合生物医学研究中心、罗恩学者心血管疾病预防常驻计划以及哈佛大学全球卫生研究所博士研究补助金。
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. 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. 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. 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. 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.