Pokrovsky S N, Afanasieva O I, Safarova M S, Balakhonova T V, Matchin Yu G, Adamova I Y U, Konovalov G A, Ezhov M V
Laboratory of Atherosclerosis, Institute of Experimental Cardiology, Federal State Institution "Russian Cardiology Research and Production Center" of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia.
Laboratory of Atherosclerosis, Institute of Experimental Cardiology, Federal State Institution "Russian Cardiology Research and Production Center" of Ministry of Health of the Russian Federation, 15A, 3d Cherepkovskaya Street, Moscow 121552, Russia.
Atheroscler Suppl. 2017 Nov;30:166-173. doi: 10.1016/j.atherosclerosissup.2017.05.004. Epub 2017 May 31.
An elevated lipoprotein(a) (Lp(a)) level is observed in more than 30% of patients with stable ischemic heart disease (SIHD). We conducted an investigation of the effects of specific Lp(a) apheresis on the progression of atherosclerosis in SIHD patients with Lp(a) levels greater than 50 mg/dL.
We prospectively enrolled 15 patients diagnosed with SIHD based on symptom-driven coronary angiography findings, with Lp(a) ≥50 mg/dL and a low density lipoprotein cholesterol (LDL-C) ≤2.5 mmol/L, who were on long-term statin therapy. They underwent weekly Lp(a) apheresis using Lp(a) Lipopak adsorption columns which contain monospecific sheep polyclonal antibodies against human Lp(a). Fifteen age and gender matched SIHD patients receiving atorvastatin monotherapy served as controls. At baseline and 18 months post-treatment, quantitative coronary angiography, intracoronary ultrasound with virtual histology and carotid ultrasound were performed. Lipid profile, including Lp(a), was measured at the scheduled visits, and before and after each apheresis procedure. Levels of high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinases (MMP)-7 and 9, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and 2 were determined at baseline and at the end of the study period.
Each specific Lp(a) apheresis procedure was carried out with two adsorption columns resulting in an average acute decrease in Lp(a) levels of 75% (from 110 ± 22 to 29 ± 16 mg/dL) without significant changes in other plasma components. Lp(a) reduction over the course of 18 months was associated with a decrease in the mean percent diameter stenosis of 5.05% and an increase in minimal lumen diameter of 14%; the mean total atheroma volume was reduced by 4.60 mm (p < 0.05 for all). There was a decrease in absolute common carotid intima-media thickness in the Lp(a) apheresis group of 0.07 ± 0.15 mm both from baseline and compared with the control group (p = 0.01). Levels of hsCRP were reduced by 40% in patients on Lp(a) apheresis without significant changes in the levels of other biomarkers at the end of the study.
Reduction of the atherosclerotic burden in coronary and carotid arteries was observed in patients treated with specific Lp(a) apheresis and statin over 18 months compared with statin therapy alone. These findings support the atherogenic role of Lp(a) and reinforce the need to assess the effects of Lp(a)-lowering on cardiovascular events and mortality. Trial Registration Clinicaltrials.gov (NCT02133807).
超过30%的稳定型缺血性心脏病（SIHD）患者的脂蛋白(a) [Lp(a)]水平升高。我们对Lp(a)水平大于50mg/dL的SIHD患者进行了特异性Lp(a)血液成分分离术对动脉粥样硬化进展影响的研究。
我们前瞻性纳入了15例基于症状驱动的冠状动脉造影结果诊断为SIHD的患者，其Lp(a)≥50mg/dL且低密度脂蛋白胆固醇（LDL-C）≤2.5mmol/L，正在接受长期他汀类药物治疗。他们使用含有抗人Lp(a)单特异性羊多克隆抗体的Lp(a) Lipopak吸附柱每周进行一次Lp(a)血液成分分离术。15例年龄和性别匹配的接受阿托伐他汀单药治疗的SIHD患者作为对照。在基线和治疗后18个月，进行定量冠状动脉造影、虚拟组织学冠状动脉内超声和颈动脉超声检查。在预定访视时以及每次血液成分分离术前和术后测量包括Lp(a)在内的血脂谱。在基线和研究期末测定高敏C反应蛋白（hsCRP）、基质金属蛋白酶（MMP）-7和9以及基质金属蛋白酶组织抑制剂（TIMP）-1和2的水平。
每次特异性Lp(a)血液成分分离术使用两个吸附柱进行，导致Lp(a)水平平均急性下降75%（从110±22降至29±16mg/dL），而其他血浆成分无显著变化。18个月期间Lp(a)的降低与平均直径狭窄百分比降低5.05%和最小管腔直径增加14%相关；平均总动脉粥样硬化体积减少4.60mm（所有p<0.05）。Lp(a)血液成分分离术组的颈总动脉内膜中层绝对厚度从基线开始以及与对照组相比均降低了0.07±0.15mm（p=0.01）。接受Lp(a)血液成分分离术的患者hsCRP水平降低了40%，研究结束时其他生物标志物水平无显著变化。
与单独使用他汀类药物治疗相比，接受特异性Lp(a)血液成分分离术和他汀类药物治疗18个月的患者冠状动脉和颈动脉的动脉粥样硬化负担减轻。这些发现支持Lp(a)的致动脉粥样硬化作用，并强化了评估降低Lp(a)对心血管事件和死亡率影响的必要性。试验注册Clinicaltrials.gov（NCT02133807）。
