Association of Lipoprotein(a) with arterial stiffness: A Mendelian randomization study

Abstract Background 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). Methods 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). Results Our analyses do not support a causal association between Lp(a) and PWV for neither measurement [β iwv (baPWV) = −.0005, p = .8 and β iwv (cfPWV) = −.006, p = .16]. The above findings were consistent across sensitivity analyses including weighted median, mode‐based estimation, MR‐Egger regression and MR‐PRESSO. Conclusion We did not find evidence indicating that Lp(a) is causally associated with PWV, the gold standard marker of arterial stiffness.