Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with very high lipoprotein (a) levels

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Atherosclerosis plus Pub Date : 2022-12-01 DOI:10.1016/j.athplu.2022.07.001
Andreja Rehberger Likozar , Miran Šebeštjen
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引用次数: 3

Abstract

Background and aims

Elevated lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol levels (LDL-C) are significant residual risk factors for cardiovascular events. Treatment with protein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduces the levels of both. Less is known about effects of PCSK9 inhibitors on functional and morphological properties of the arterial wall. The aim of the present study was to determine whether other factors besides decreased LDL-C and Lp(a) are associated with functional (flow-mediated dilation [FMD]) and morphological (carotid intima-media thickness [c-IMT], pulse-wave velocity [PWV]) changes of the arterial wall properties in patients with coronary artery disease (CAD) treated with alirocumab and evolocumab.

Methods

One hundred patients with CAD after myocardial infarction before 55 years and with high Lp(a) were randomised to lipid-lowering therapies without PCSK9 inhibitors (control; N = 31), or with alirocumab 150 mg SC (N = 35) or evolocumab 140 mg SC (N = 34), every 2 weeks. All patients underwent blood sampling for biochemical analyses and ultrasound measurements for FMD, c-IMT and PWV.

Results

There were no significant changes in FMD for the control (10.7% ± 6.6%–11.1% ± 4.4%, p = 0.716) and alirocumab (10.7% ± 5.9%–11.2% ± 5.3%, p = 0.547) groups, while evolocumab promoted significant increase (11.2% ± 6.8%–14.1% ± 6.6%, p < 0.0001). Only in non-smokers and non-diabetics significant improvements in FMD (p < 0.0001) after treatment with PCSK9 inhibitors were observed.

Conclusion

These data show that for patients with CAD and high Lp(a) levels, beneficial effects of PCSK9 inhibitors on the arterial wall properties can be attenuated by specific risk factors, such as smoking and diabetes.

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吸烟和糖尿病会减弱PSCK9抑制剂对非常高脂蛋白(a)水平患者动脉壁特性的有益作用
背景和目的脂蛋白(Lp(a))升高和低密度脂蛋白胆固醇(LDL-C)水平是心血管事件的重要残留危险因素。用蛋白转化酶枯草杆菌蛋白9型(PCSK9)抑制剂治疗可降低两者的水平。目前对PCSK9抑制剂对动脉壁功能和形态特性的影响知之甚少。本研究的目的是确定除了降低LDL-C和Lp(a)外,其他因素是否与alirocumab和evolocumab治疗的冠心病(CAD)患者动脉壁特性的功能(血流介导的扩张[FMD])和形态学(颈动脉内膜-中膜厚度[c-IMT],脉搏波速度[PWV])变化有关。方法100例55岁前高Lp(a)心肌梗死后冠心病患者随机分为无PCSK9抑制剂的降脂治疗组(对照组;N = 31),或alirocumab 150 mg SC (N = 35)或evolocumab 140 mg SC (N = 34),每2周一次。所有患者均接受血液采样进行生化分析和FMD、c-IMT和PWV的超声检测。结果对照组(10.7%±6.6% ~ 11.1%±4.4%,p = 0.716)和alirocumab组(10.7%±5.9% ~ 11.2%±5.3%,p = 0.547) FMD无显著变化,而evolocumab组FMD显著升高(11.2%±6.8% ~ 14.1%±6.6%,p <0.0001)。仅在非吸烟者和非糖尿病患者中FMD有显著改善(p <0.0001)。这些数据表明,对于冠心病和高Lp(a)水平的患者,PCSK9抑制剂对动脉壁特性的有益作用可能会因吸烟和糖尿病等特定危险因素而减弱。
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来源期刊
Atherosclerosis plus
Atherosclerosis plus Cardiology and Cardiovascular Medicine
CiteScore
2.60
自引率
0.00%
发文量
0
审稿时长
66 days
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