Björkbacka Harry, Alm Ragnar, Persson Margaretha, Hedblad Bo, Nilsson Jan, Fredrikson Gunilla Nordin
From the Department of Clinical Sciences, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
Arterioscler Thromb Vasc Biol. 2016 Apr;36(4):765-71. doi: 10.1161/ATVBAHA.115.306938. Epub 2016 Feb 25.
Previous smaller studies have indicated inverse associations between autoantibodies to oxidized low-density lipoprotein epitopes, and cardiovascular disease. The present study investigated associations between autoantibodies against the apolipoprotein B-100 peptides p45 and p210, respectively, and risk of incident cardiovascular disease in a large population-based cohort.
Apolipoprotein B-100 autoantibodies were analyzed by ELISA in a prospective study, including 5393 individuals (aged 46-68 years) belonging to the cardiovascular arm of the Malmö Diet and Cancer study with a follow-up time of >15 years. Subjects that suffered an acute coronary event during follow-up (n=382) had lower levels at baseline of IgM autoantibodies recognizing the native and malondialdehyde-modified apolipoprotein B-100 peptides p45 and p210 and also lower IgG levels recognizing native p210, whereas no association was found with risk for stroke (n=317). Subjects in the highest compared with lowest tertile of IgM-p45MDA (hazard ratio [95% confidence interval]: 0.72 [0.55, 0.94]; P=0.017) and IgG-p210native (hazard ratio [95% confidence interval]: 0.73 [0.56, 0.97]; P=0.029) had lower risk for incident coronary events after adjustment for cardiovascular risk factors in Cox proportional hazard regression models. Moreover, subjects with high levels of IgG-p210native were less likely to have carotid plaques as assessed by ultrasonography at baseline (odds ratio=0.81, 95% confidence interval 0.70-0.95, P=0.008 after adjustment for risk factors).
This large prospective study demonstrates that subjects with high levels of apolipoprotein B-100 autoantibodies have a lower risk of coronary events supporting a protective role of these autoantibodies in cardiovascular disease.
以往规模较小的研究表明,氧化型低密度脂蛋白表位自身抗体与心血管疾病之间存在负相关。本研究在一个大型人群队列中,分别调查了抗载脂蛋白B-100肽p45和p210自身抗体与心血管疾病发病风险之间的关联。
在一项前瞻性研究中,采用酶联免疫吸附测定法(ELISA)分析了5393名(年龄46 - 68岁)属于马尔默饮食与癌症研究心血管队列的个体的载脂蛋白B-100自身抗体,随访时间超过15年。随访期间发生急性冠状动脉事件的受试者(n = 382),识别天然和丙二醛修饰的载脂蛋白B-100肽p45和p210的IgM自身抗体在基线时水平较低,识别天然p210的IgG水平也较低,而未发现与中风风险(n = 317)有关联。在Cox比例风险回归模型中,校正心血管危险因素后,IgM-p45MDA最高三分位数组与最低三分位数组相比的受试者(风险比[95%置信区间]:0.72[0.55, 0.94];P = 0.017)以及IgG-p210天然型最高三分位数组与最低三分位数组相比的受试者(风险比[95%置信区间]:0.73[0.56, 0.97];P = 0.029)发生冠状动脉事件的风险较低。此外,基线时通过超声检查评估,IgG-p210天然型水平高的受试者颈动脉斑块形成的可能性较小(优势比 = 0.81,95%置信区间0.70 - 0.95,校正危险因素后P = 0.008)。
这项大型前瞻性研究表明,载脂蛋白B-100自身抗体水平高的受试者发生冠状动脉事件的风险较低,支持这些自身抗体在心血管疾病中起保护作用。