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.

Keywords: Lp(a); Mendelian randomization; PWV; arterial stiffness; causal association; general population.