Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
School of Biomedical Engineering and Imaging Sciences, Kings College London, London, UK.
Eur J Clin Invest. 2024 May;54(5):e14168. doi: 10.1111/eci.14168. Epub 2024 Jan 18.
In this study we used Mendelian randomization (MR) to investigate the potential causal association of lipoprotein (a) [Lp(a)] levels with pulse wave velocity (PWV).
Genetic variants associated with Lp(a) were retrieved from the UK Biobank GWAS (N = 290,497). A non- overlapping GWAS based on a European cohort (N = 7,000) was used to obtain genetic associations with PWV (outcome) and utilized two different measures for the same trait, brachial-ankle (baPWV) and carotid-femoral (cfPWV) PWV. We applied a two-sample MR using the inverse variance weighting method (IVW) and a series of sensitivity analyses for 170 SNPs that were selected as instrumental variables (IVs).
Our analyses do not support a causal association between Lp(a) and PWV for neither measurement [β(baPWV) = -.0005, p = .8 and β(cfPWV) = -.006, p = .16]. The above findings were consistent across sensitivity analyses including weighted median, mode-based estimation, MR-Egger regression and MR-PRESSO.
We did not find evidence indicating that Lp(a) is causally associated with PWV, the gold standard marker of arterial stiffness.
本研究采用孟德尔随机化（MR）方法，探讨脂蛋白（a）[Lp(a)]水平与脉搏波速度（PWV）之间潜在的因果关联。
从英国生物银行 GWAS（N=290497）中检索与 Lp(a)相关的遗传变异。利用基于欧洲队列的非重叠 GWAS（N=7000）获得与 PWV（结局）相关的遗传关联，并利用两种不同的方法测量同一特征，即肱踝脉搏波速度（baPWV）和颈股脉搏波速度（cfPWV）。我们应用两样本 MR 方法，采用逆方差加权法（IVW）和一系列敏感性分析，对 170 个被选为工具变量（IVs）的 SNP 进行分析。
我们的分析结果不支持 Lp(a)与 PWV 之间存在因果关系，无论是使用 baPWV 还是 cfPWV 测量[baPWV：β=-0.0005，p=0.8；cfPWV：β=-0.006，p=0.16]。敏感性分析结果包括加权中位数、基于模式的估计、MR-Egger 回归和 MR-PRESSO，结果均一致。
我们没有发现证据表明 Lp(a)与动脉僵硬度的金标准标志物 PWV 之间存在因果关系。
