2nd Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece; Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece.
Michaelidion Cardiac Center, University of Ioannina, Ioannina, Greece; Department of Cardiology, 1st IKA General Hospital, Athens, Greece.
J Clin Lipidol. 2018 Mar-Apr;12(2):338-347. doi: 10.1016/j.jacl.2017.12.004. Epub 2017 Dec 19.
Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease (CVD), and proinflammatory interleukin-1 (IL-1) genotypes may influence Lp(a)-mediated CVD events. The genotype IL-1(+) is associated with higher rates of inflammation than IL-1(-) genotype. Targeting IL-1β was recently shown to decrease CVD events independent of low-density lipoprotein-cholesterol levels.
The objective of the study is to assess the modulatory effect of IL-1 genotypes on risk mediated by Lp(a) METHODS: We assessed whether IL-1 genotypes modulate the effect of Lp(a) on major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke/transient ischemic attack) and angiographically determined coronary artery disease (CAD). IL-1 genotypes and Lp(a) were measured in 603 patients without diabetes mellitus undergoing angiography. Major adverse cardiovascular events and CAD were assessed over a median of 45 months.
In multivariable-adjusted analysis, Lp(a) was associated with major adverse cardiovascular events (hazard ratio [HR] [95% confidence interval {CI}]: 2.95 [1.16-7.54], P = .023) and CAD (odds ratio [OR] [95% CI]: 1.84 [1.12-3.03], P = .016) comparing quartile 4 vs quartile 1. In Cox regression analysis, IL-1(+) patients with Lp(a) above the median (>9.2 mg/dL) had a worse event-free cumulative survival (HR [95% CI]: 3.59 [1.07-12.03], P = .039) compared to IL-1(-) patients with Lp(a) below the median. In IL-1(+) patients aged ≤60 years, Lp(a) was also associated with angiographically determined CAD (OR [95% CI]: 2.90 [1.07-7.86], P = .036) comparing quartile 4 vs quartile 1 but not IL-1(-) patients.
Proinflammatory IL-1(+) genotypes modulate the risk of Lp(a) long-term CVD events and CAD. These data suggest that the dual genetic contributions of elevated Lp(a) levels and IL-1(+) genotypes may identify younger subjects at particularly high risk for CVD events.
脂蛋白(a)[Lp(a)]是心血管疾病（CVD）的遗传风险因素，促炎细胞因子白细胞介素-1（IL-1）基因型可能影响 Lp(a)介导的 CVD 事件。IL-1(+)基因型与更高的炎症率相关，而 IL-1(-)基因型则较低。最近的研究表明，靶向 IL-1β 可降低 CVD 事件的发生，而不依赖于低密度脂蛋白胆固醇水平。
本研究旨在评估 IL-1 基因型对 Lp(a)介导的风险的调节作用。
我们评估了 IL-1 基因型是否调节 Lp(a)对主要不良心血管事件（心血管死亡、心肌梗死和卒中和短暂性脑缺血发作）和血管造影确定的冠状动脉疾病（CAD）的影响。在接受血管造影的 603 例无糖尿病患者中，检测了 IL-1 基因型和 Lp(a)。在中位数为 45 个月的时间内，评估了主要不良心血管事件和 CAD。
多变量调整分析显示，Lp(a)与主要不良心血管事件（风险比[HR] [95%置信区间{CI}]：2.95 [1.16-7.54]，P=0.023）和 CAD（比值比[OR] [95% CI]：1.84 [1.12-3.03]，P=0.016）相关，与第 4 四分位与第 1 四分位相比。在 Cox 回归分析中，Lp(a)高于中位数（>9.2mg/dL）的 IL-1(+)患者的无事件累积生存率较差（HR [95% CI]：3.59 [1.07-12.03]，P=0.039）与 Lp(a)低于中位数的 IL-1(-)患者相比。在年龄≤60 岁的 IL-1(+)患者中，Lp(a)也与血管造影确定的 CAD 相关（OR [95% CI]：2.90 [1.07-7.86]，P=0.036），与第 4 四分位与第 1 四分位相比，但与 IL-1(-)患者无关。
促炎的 IL-1(+)基因型调节 Lp(a) 长期 CVD 事件和 CAD 的风险。这些数据表明，升高的 Lp(a)水平和 IL-1(+)基因型的双重遗传贡献可能会识别出处于特别高 CVD 风险的年轻患者。
