Sources and magnitudes of relative risks for the effects of metabolic risk factors on disease-specific mortality.

aSee Danaei et al. [61] for sensitivity to using RRs from systematic reviews of other epidemiological studies.bFor these risk factor�Cdisease pairs, RRs in the source were reported for all ages combined. We used median age at event and the age pattern of excess risk from another risk factor and the same disease (e.g., age pattern of total serum cholesterol and ischemic stroke was applied to LDL and ischemic stroke) or from the same risk factor and another disease (e.g., age pattern of excess risk for SBP and all cardiovascular diseases was applied to SBP and hypertensive disease) to estimate RRs for each age category.cWe used a null association in those 70-y-old and older because RRs in two large meta-analyses of prospective studies [95], [97] were not statistically significant from null, and did not show consistent benefits for lower total cholesterol in these ages. There is some evidence from clinical trials that statins reduce the risk of stroke in older ages [98]. However, statins may reduce stroke mortality through other, non-cholesterol mechanisms such as stabilization of atherosclerotic plaques [99]. In the sensitivity analysis for high LDL cholesterol and ischemic stroke, we used an RR of 1.12 in these age groups.dThis category includes rheumatic heart disease, acute and subacute endocarditis, cardiomyopathy, other inflammatory cardiac diseases, valvular disorders, aortic aneurysm, pulmonary embolism, conduction disorders, peripheral vascular disorders, and other ill-defined cardiovascular diseases.eWe used meta-analyses of studies with measured weight and height because using self-reported weight and height can lead to bias in estimated RRs. The correlation between self-reported and measured weight, as found in selected studies [100], [101], does not remove the possibility of bias because even with perfect correlation, the absolute bias in self-reported weight and height may be a function of its true value.fThe RRs reported for Asian and Australia�CNew Zealand populations were not significantly different in this meta-analysis providing empirical evidence on absence of significant effect modification in the multiplicative scale by ethnicity. A meta-analysis of studies in Europe and North America included studies [102] with self-reported height and weight and was thus not used in this analysis. The RRs reported in that meta-analysis ranged from 1.02 to 1.26 and the average RR weighted by number of cases was 1.07 per kg/m2 which is almost equal to the RR for 60- to 69-y-olds in this analysis.APCSC, Asia-Pacific Cohorts Studies Collaboration; PSC, Prospective Studies Collaboration.a. 有关其他流行病学研究的系统综述中使用相对风险（Relative Risk, RR）的敏感性分析，请参见Danaei等人[61]的研究。 b. 针对此类危险因素-疾病配对，源文献中仅报告了全年龄段合并的相对风险。我们采用事件发生时的中位年龄，以及另一危险因素与同一疾病的超额风险年龄模式（例如，将总血清胆固醇与缺血性脑卒中的年龄模式应用于低密度脂蛋白（Low-Density Lipoprotein, LDL）与缺血性脑卒中），或同一危险因素与另一疾病的超额风险年龄模式（例如，将收缩压（Systolic Blood Pressure, SBP）与所有心血管疾病的超额风险年龄模式应用于收缩压与高血压病），以此估算各年龄组的相对风险。 c. 我们将70岁及以上人群的关联设为无效，因为两项大型前瞻性研究荟萃分析[95]、[97]显示，其相对风险与无效值无统计学差异，且未观察到更低的总胆固醇水平能带来一致的获益。现有临床试验证据表明，他汀类药物（statins）可降低老年人群的脑卒中风险[98]。不过，他汀类药物可能通过非胆固醇依赖的其他机制降低脑卒中死亡率，例如稳定动脉粥样硬化斑块（atherosclerotic plaques）[99]。在针对高低密度脂蛋白与缺血性脑卒中的敏感性分析中，我们将该年龄组的相对风险设为1.12。 d. 该类别涵盖风湿性心脏病、急性与亚急性心内膜炎、心肌病、其他炎性心脏病、瓣膜疾病、主动脉瘤、肺栓塞、传导障碍、外周血管疾病，以及其他定义不明的心血管疾病。 e. 我们采用了经测量体重与身高的研究的荟萃分析结果，因为使用自我报告的体重与身高可能会导致相对风险估算出现偏倚。如部分已入选研究[100]、[101]所示，自我报告与实测体重间的相关性并不能消除偏倚发生的可能：即便二者完全相关，自我报告的体重与身高的绝对偏倚仍可能随其真实值变化而变化。 f. 本次荟萃分析中，亚洲及澳大利亚-新西兰人群报告的相对风险无显著差异，这为乘法尺度上未出现具有统计学意义的种族效应修饰提供了实证依据。一项纳入欧洲与北美研究的荟萃分析[102]采用了自我报告的身高与体重，因此未被纳入本次分析。该荟萃分析报告的相对风险范围为1.02至1.26，按病例数加权的平均相对风险为每kg/m² 1.07，与本次分析中60至69岁年龄组的相对风险几乎一致。 APCSC，亚太队列研究协作组（Asia-Pacific Cohorts Studies Collaboration）；PSC，前瞻性研究协作组（Prospective Studies Collaboration）。