Department of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Duesseldorf, Germany.
Department of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty, Heinrich-Heine University, Duesseldorf, Germany; Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom; Department of Vascular Medicine, Surrey and Sussex NHS Healthcare Trust, Redhill, United Kingdom.
Microvasc Res. 2023 Jul;148:104513. doi: 10.1016/j.mvr.2023.104513. Epub 2023 Mar 3.
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively decrease low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events in patients at very high cardiovascular risk. Recent short-term studies suggest a partially LDL-C independent beneficial effect of PCSK9 inhibitor (PCSK9i) therapy on endothelial function and arterial stiffness, whereas it is unknown if this effect persists and what the effect is on microcirculation.
To investigate the effects of PCSK9i therapy on vascular parameters beyond its lipid lowering effect.
In this prospective trial, 32 patients at very high cardiovascular risk and indication for PCSK9i therapy were included. Measurements were performed at baseline and after 6 months of PCSK9i treatment. Endothelial function was assessed as flow-mediated dilation (FMD). Arterial stiffness was measured as pulse wave velocity (PWV) and aortic augmentation index (AIx). Peripheral tissue oxygenation (StO) as a marker of microvascular function was assessed at the distal extremities using near-infrared spectroscopy camera.
Six months of PCSK9i therapy decreased LDL-C levels from 141 ± 54 to 60 ± 30 mg/dl (-56 ± 21 %, p < 0.001), FMD significantly increased from 5.4 ± 1.7 % to 6.4 ± 1.9 % (+19 ± 10 %, p < 0.001), PWV decreased in male patients significantly from 8.9 ± 2.1 to 7.9 ± 1.5 m/s (-12 ± 9 %, p = 0.025). AIx decreased from 27.1 ± 10.4 % to 23.0 ± 9.7 % (-16 ± 14 %, p < 0.001), StO significantly increased from 67 ± 12 % to 71 ± 11 % (+7 ± 6 %, p = 0.012). Brachial and aortic blood pressure showed no significant changes after six months. There was no correlation between LDL-C reduction and changes in vascular parameters.
Chronic PCSK9i therapy is associated with sustained improvements in endothelial function, arterial stiffness, and microvascular function independent from lipid lowering.
前蛋白转化酶枯草溶菌素 9 抑制剂（PCSK9i）可有效降低低密度脂蛋白胆固醇（LDL-C），降低极高心血管风险患者的心血管事件发生率。近期的短期研究表明，PCSK9 抑制剂（PCSK9i）治疗对内皮功能和动脉僵硬度具有部分 LDL-C 非依赖性的有益作用，然而，尚不清楚这种作用是否持续，以及对微循环的影响如何。
研究 PCSK9i 治疗除降脂作用以外对血管参数的影响。
在这项前瞻性试验中，纳入了 32 例极高心血管风险且需要 PCSK9i 治疗的患者。在基线时和 PCSK9i 治疗 6 个月时进行测量。内皮功能评估采用血流介导的舒张功能（FMD）。动脉僵硬度通过脉搏波速度（PWV）和主动脉增强指数（AIx）进行测量。使用近红外光谱摄像机评估外周组织氧合（StO）作为微血管功能的标志物。
PCSK9i 治疗 6 个月后，LDL-C 水平从 141±54 降至 60±30 mg/dl（-56±21%，p<0.001），FMD 从 5.4±1.7%显著增加至 6.4±1.9%（+19±10%，p<0.001），男性患者的 PWV 从 8.9±2.1 降至 7.9±1.5 m/s（-12±9%，p=0.025）。AIx 从 27.1±10.4%降至 23.0±9.7%（-16±14%，p<0.001），StO 从 67±12%显著增加至 71±11%（+7±6%，p=0.012）。肱动脉和主动脉血压在 6 个月后无显著变化。LDL-C 降低与血管参数变化之间无相关性。
慢性 PCSK9i 治疗与内皮功能、动脉僵硬度和微血管功能的持续改善相关，而与降脂作用无关。
