CarVasCare Research Group (2023-GRIN-34459), Faculta de Enfermería de Cuenca, Universidad de Castilla-La Mancha, Cuenca, Spain.
Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile.
Eur J Clin Invest. 2024 Oct;54(10):e14269. doi: 10.1111/eci.14269. Epub 2024 Jun 21.
Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction.
A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness.
Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: -2.61 m/s [95% CI: -3.70, -1.52]; ES: -1.62 [95% CI: -2.53, -.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics.
The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction.
动脉粥样硬化是导致死亡率的主要原因，需要有效控制高胆固醇血症，特别是升高的低密度脂蛋白胆固醇（LDL-C）。前蛋白转化酶枯草溶菌素/ kexin 9 抑制剂（PCSK9i）的出现彻底改变了降脂治疗。PCSK9i 可显著降低 LDL-C 并带来心血管益处，特别是在他汀类药物不耐受或无反应的患者中。然而，PCSK9i 的潜在多效性作用，尤其是对动脉僵硬度的影响，仍是研究的课题。本系统评价和荟萃分析旨在深入了解 PCSK9i 的潜在多效性作用，特别是对动脉健康的影响。主要目的是分析 PCSK9i 对动脉僵硬度的影响，超越传统的降脂指标，为降低心血管风险提供更全面的方法。
系统检索了主要数据库、临床试验注册处和灰色文献。纳入标准包括接受 PCSK9i 增强降脂治疗的前瞻性队列研究中的成年人，重点是通过脉搏波速度（PWv）测量的动脉僵硬度。采用随机效应荟萃分析、敏感性分析和荟萃回归模型评估在降脂干预中添加 PCSK9i 对动脉僵硬度的综合影响。
有 5 项研究（158 名参与者）符合纳入标准，表明在降脂干预中添加 PCSK9i 后 PWv 显著降低（平均差异：-2.61m/s [95% CI：-3.70，-1.52]；ES：-1.62 [95% CI：-2.53，-.71]）。亚组分析和荟萃回归模型提示可能存在基于性别的和基于基线 PWv 的差异，强调了患者的个体特征。
荟萃分析提供了强有力的证据，表明在降脂干预中添加 PCSK9i 可显著改善动脉僵硬度，表明除了降低 LDL-C 之外，还具有更广泛的血管益处。
