Relationship Between Mean Platelet Volume and Cardiac Hypertrophy and Mediating Effect of Vanillic Acid Glycine Levels in Plasma Metabolites: A Mendelian Randomization Study

Background There is growing evidence that platelet‐related parameters can influence a wide range of cardiovascular diseases. However, the effect of platelet‐related parameters on cardiac hypertrophy is unknown. To verify this, the present study proposes to use Mendelian randomization (MR) to explore bidirectional causality between multiple platelet‐related parameters and cardiac hypertrophy and to assess the potential mediating role of plasma metabolites. Methods Single‐nucleotide polymorphisms (SNPs), the instrumental variable required for the study, were obtained through the public genome‐wide association study (GWAS) database, and samples were obtained from European populations. We obtained summary statistics of cardiac hypertrophy (4113 cases, 839,403 controls) after GWAS meta‐analysis of two independent datasets. In this study, we mainly used the inverse variance weighted (IVW) method to assess the causal effect; two‐step MR analysis was used to assess the mediating effect. Results MR analysis showed a positive causal relationship between mean platelet volume (MPV) and the risk of cardiac hypertrophy (odds ratio, 1.72 for cardiac hypertrophy per one‐standard‐deviation increment in MPV; 95% confidence interval, 1.24 to 2.38; p = 0.001). Multivariate MR showed that the risk role of MPV in promoting cardiac hypertrophy persisted after adjustment for other platelet parameters. Mediation analysis via two‐step MR showed that this effect was partially mediated by vanillic acid glycine levels, with a mediation ratio of 20.4% (95% confidence interval, 3.7% to 40.7%). Conclusions This study revealed a positive causal relationship between MPV and cardiac hypertrophy risk, partly mediated by plasma vanillic acid glycine levels.