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冠状动脉旁路移植术后脂蛋白(a)水平与短期和长期预后的关系:脂蛋白分离术的作用。

Association of lipoprotein(a) level with short- and long-term outcomes after CABG: The role of lipoprotein apheresis.

作者信息

Ezhov Marat V, Afanasieva Olga I, Il'ina Larisa N, Safarova Maya S, Adamova Irina Yu, Matchin Yuri G, Konovalov Gennady A, Akchurin Renat S, Pokrovsky Sergei N

机构信息

Cardiology Research Center, 3rd Cherepkovskaya Street, 15a, 121552, Moscow, Russia.

MEDSI Clinic, Georgian Lane, 3a, 123056, Moscow, Russia.

出版信息

Atheroscler Suppl. 2017 Nov;30:187-192. doi: 10.1016/j.atherosclerosissup.2017.05.011. Epub 2017 May 31.

Abstract

OBJECTIVE

To evaluate the association of lipoprotein(a) [Lp(a)] level with short- and long-term outcomes after coronary artery bypass grafting (CABG) and to assess the effect of a 12 month course of weekly lipoprotein apheresis on vein graft patency and coronary atherosclerosis course in post-CABG patients with hyperlipidemia.

METHODS

This study was performed in patients after successful CABG and consisted of three parts: a) a retrospective part with computed tomography assessment of vein graft patency in patients with first-year recurrence of chest pain after CABG (n = 102); b) a prospective trial with evaluation of cardiovascular outcomes during follow up time up to 15 years in relation to baseline Lp(a) levels (n = 356); c) an 12-months interventional controlled study in 50 patients with low-density lipoprotein cholesterol (LDL-C) levels >2.6 mmol/L prior to the operation despite statin treatment that allocated into 2 groups: active (n = 25, weekly apheresis by cascade plasma filtration (CPF) plus atorvastatin), and control (n = 25, atorvastatin alone).

RESULTS

Patients subjected to computed tomography were divided in two groups: 66 (65%) with at least one vein graft occlusion and 36 (35%) without occlusions. Lp(a) levels were significantly higher in patients with occluded grafts with a median (95% confidence intervals (CI)) of 24 (17-42) mg/dL vs. 12 (6-24) mg/dL in patients with patent grafts, p < 0.01. Over a mean of 8.5 ± 3.5 years (range 0.9-15.0 years), the primary and secondary endpoints were registered in 46 (13%) and 107 (30%) patients, respectively. Patients with Lp(a) ≥30 mg/dL were at significantly greater risk for the primary endpoint (hazard ratio (HR) 2.98, 95% confidence interval (CI) 1.76-5.03, p < 0.001) and secondary endpoint (HR 3.47, 95%CI 2.48-4.85, p < 0.001) than patients with Lp(a) values <30 mg/dL. During the CPF procedure LDL-C levels decreased by 59 ± 14%, Lp(a) levels by 49 ± 15. The frequency of vein graft occlusions at study end was 14.3% (11 of 77) in the apheresis group and 27.4% (23 of 84) in the control group, p < 0.05. Progression of atherosclerosis was obtained in 26 (14.2%) segments of native coronary arteries in the apheresis group and in 50 (25.0%) segments of the control group. Regression signs were found in 30 (16.4%) and 19 (9.5%) segments, stabilization in 127 (69.4%) and 131 (65.5%) segments, respectively (χ = 9.37, p < 0.01). A Lp(a) level higher than 30 mg/dL was associated with a three-fold increased risk of vein grafts occlusion during first year after CABG, p < 0.001.

CONCLUSION

Our data suggest that elevated Lp(a) is associated with a significantly increasing rate of one-year vein graft occlusions and adverse long-term cardiovascular outcomes whereas the use of lipoprotein apheresis improves vein graft patency during the first year after CABG.

摘要

目的

评估脂蛋白(a)[Lp(a)]水平与冠状动脉旁路移植术(CABG)后短期和长期预后的相关性,并评估为期12个月的每周一次脂蛋白分离术对CABG术后高脂血症患者静脉移植物通畅率和冠状动脉粥样硬化进程的影响。

方法

本研究在成功进行CABG的患者中开展,包括三个部分:a)回顾性部分,对CABG术后第一年出现胸痛复发的患者(n = 102)进行计算机断层扫描评估静脉移植物通畅情况;b)前瞻性试验,评估随访长达15年期间与基线Lp(a)水平相关的心血管结局(n = 356);c)一项为期12个月的干预性对照研究,纳入50例术前尽管接受他汀类药物治疗但低密度脂蛋白胆固醇(LDL-C)水平>2.6 mmol/L的患者,分为两组:活性组(n = 25,采用级联血浆滤过(CPF)每周进行一次血液成分分离术加阿托伐他汀)和对照组(n = 25,仅使用阿托伐他汀)。

结果

接受计算机断层扫描评估的患者分为两组:66例(65%)至少有一处静脉移植物闭塞,36例(35%)无闭塞。闭塞移植物患者的Lp(a)水平显著更高,中位数(95%置信区间(CI))为24(17 - 42)mg/dL,而移植物通畅患者为12(6 - 24)mg/dL,p < 0.01。在平均8.5 ± 3.5年(范围0.9 - 15.0年)期间,分别有46例(13%)和107例(30%)患者出现主要终点和次要终点。Lp(a)≥30 mg/dL的患者发生主要终点的风险显著高于Lp(a)值<30 mg/dL的患者(风险比(HR)2.98,95%置信区间(CI)1.76 - 5.03,p < 0.001)和次要终点(HR 3.47,95%CI 2.48 - 4.85,p < 0.001)。在CPF过程中,LDL-C水平降低了59 ± 14%,Lp(a)水平降低了49 ± 15%。研究结束时,血液成分分离术组静脉移植物闭塞的发生率为14.3%(77例中的11例),对照组为27.4%(84例中的23例),p < 0.05。血液成分分离术组有26段(14.2%)自身冠状动脉出现动脉粥样硬化进展,对照组有50段(25.0%)。分别在30段(16.4%)和19段(9.5%)发现了动脉粥样硬化消退迹象,在127段(69.4%)和131段(65.5%)发现了稳定迹象(χ = 9.37,p < 0.01)。Lp(a)水平高于30 mg/dL与CABG术后第一年静脉移植物闭塞风险增加三倍相关,p < 0.001。

结论

我们的数据表明,Lp(a)升高与一年期静脉移植物闭塞率显著增加及不良长期心血管结局相关,而脂蛋白分离术的应用可改善CABG术后第一年的静脉移植物通畅率。

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