低密度脂蛋白胆固醇累积暴露对新发急性心肌梗死影响的前瞻性队列研究

目的:探讨低密度脂蛋白胆固醇(LDL-C)累积暴露对新发急性心肌梗死(AMI)的影响。方法:以开滦研究中满足标准的观察对象组成研究队列。依据多次LDL-C测量值计算的LDL-C升高累积暴露时间及LDL-C累积暴露值(cumLDL-C)进行分组,采用log-rank检验比较不同LDL-C升高累积暴露时间组及LDL-C累积暴露值组在随访期间新发AMI累积发病率的差异,采用多因素Cox回归模型分析不同LDL-C累积暴露对新发AMI的影响,分别删除服用降脂药、降压药、降糖药人群后,重复Cox回归模型,进行敏感性分析。结果:51407例观察对象纳入研究,平均年龄(52.70±11.92)岁,其中男性39120例(75.12%),平均随访(6.84±0.89)年。LDL-C升高累积暴露0年有37941例(73.81%),累积暴露2年有9361例(18.21%),累积暴露4年有3205例(6.23%),累积暴露6年有900例(1.75%)。LDL-C升高累积暴露0年、2年、4年、6年人群的AMI累积发病率分别为0.73%、1.12%、1.50%和2.10%,差异有统计学意义(χ2=36.87,P<0.001)。经多因素Cox回归分析显示,校正其他混杂因素后,与LDL-C升高累积暴露0年相比,LDL-C升高累积暴露2年、4年、6年人群发生AMI的HR(95%CI)分别是1.28(1.00~1.63)、1.61(1.15~2.25)、2.08(1.23~3.51);与cumLDL-C第一分位组相比,cumLDL-C第二分位组、第三分位组发生AMI的HR(95%CI)分别1.19(0.91~1.55)、1.39(1.08~1.80)。增加校正2006年度单次LDL-C测量值后,与LDL-C升高累积暴露0年相比,LDL-C升高累积暴露2年、4年、6年人群发生AMI的HR(95%CI)分别是1.29(1.00~1.65)、1.64(1.13~2.38)、2.15(1.20~3.84);与cumLDL-C第一分位组相比,cumLDL-C第二分位组、第三分位组发生AMI的HR(95%CI)分别1.18(0.89~1.56)、1.37(1.01~1.86)。分别删除服用降脂药、降压药、降糖药人群后,进行敏感性分析,结果与以上主要研究结果趋势一致。结论:LDL-C的长期变化呈“累积暴露”现象,LDL-C累积暴露是AMI的危险因素,且独立于单次LDL-C测量值。

A Prospective Cohort Study of the Effect of Cumulative Exposure to Low Density Lipoprotein Cholesterol on New-onset Acute Myocardial Infarction

Objectives:To explore the effect of cumulative exposure to low density lipoprotein cholesterol(LDL-C)on new onset acute myocardial infarction(AMI).Methods:We enrolled participants from the Kailuan group,who met the specific criteria for this study.Participants were grouped according to the different years of cumulative exposure to elevated LDL-C(cumLDL-C)calculated by the repeated LDL-C measured values.Log-rank test was performed to compare cumulative incidence of AMI in different cumLDL-C groups during the follow-up period.Multivariate Cox regression analysis was conducted to explore the effect of cumLDL-C on new onset AMI.The sensitivity analysis was performed after deleting the participants taking lipid-lowering drugs,antihypertensive drugs and hypoglycemic drugs.Results:51407 participants were included in this study,with an average age of(52.70±11.92)years.Among them,39120(75.12%)were males.According to cumulative exposure years of elevated LDL-C,the participants were divided into four groups:cumulative exposure 0 years,n=37941(73.81%),cumulative exposure 2 years,n=9361(18.21%),cumulative exposure 4 years,n=3205(6.23%);cumulative exposure 6 years,n=900(1.75%).The cumulative incidence of AMI in each group was 0.73%,1.12%,1.50%,2.10%,respectively(χ2=36.87,P<0.001).After adjusting confounding factors,multivariate Cox regression analysis showed that compared with the participants in cumulative exposure with elevated LDL-C 0 years group,HR(95%CI)of the other groups of new onset AMI were 1.28(1.00-1.63),1.61(1.15-2.25),and 2.08(1.23-3.51),respectively.Compared with the cumLDL-C 1st tertile subgroup,HR(95%CI)of the 2nd and 3rd tertile groups of new onset AMI were 1.19(0.91-1.55)and 1.39(1.08-1.80),respectively.After further adjusting the LDL-C value measured at 2006 health examination,compared with the participants in cumulative exposure with elevated LDL-C 0 years group,HR(95%CI)of the other groups of new onset AMI were 1.29(1.00-1.65),1.64(1.13-2.38),2.15(1.20-3.84),respectively.Compared with the cumLDL-C 1st tertile subgroup,HR(95%CI)of the 2nd and 3rd tertile subgroups of new onset AMI were 1.18(0.89-1.56),1.37(1.01-1.86),respectively.Results of the sensitivity analysis were similar as above.Conclusions:The long-term change of LDL-C shows"cumulative exposure"effect,and cumulative exposure to LDL-C is a risk factor for new onset AMI,independent of single LDL-C measurement.