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The Role of Iron and Other Micronutrients in Arterial Stiffness: Univariable and Multivariable Mendelian Randomization

Year: 2025

Type: article

Abstract: Background: Prior research on the relationship between iron status and arterial stiffness is limited, with causality still unclear. However, understanding these connections is crucial for improving the prevention and management of arterial stiffness. Therefore, this study aimed to examine the impact of iron status and other micronutrients on arterial stiffness risk using Mendelian randomization (MR) approaches. Methods: MR was performed utilizing genome-wide association studies (GWAS) data from European populations to investigate the causal link between various nutrients (iron, etc.) and arterial stiffness index. We selected the random-effects inverse-variance weighting (IVW) approach for the primary analysis and conducted numerous sensitivity tests to ensure accuracy. Results: This study found a causal effect of genetically predicted high levels of serum iron (β = 0.069, 95% confidence interval (CI) [0.031 to 0.107], pFDR = 1.87 × 10-3) [false discovery rate, FDR], ferritin (β = 0.143, 95% CI [0.050 to 0.235], pFDR = 8.28 × 10-3), and transferrin saturation (β = 0.053, 95% CI [0.025 to 0.080], pFDR = 1.29 × 10-3) on arterial stiffness index. There was no evidence of reverse causality. Associations derived from multivariate MR analyses remained significant after adjusting for potential confounders. Zinc and carotene levels may be inversely linked with arterial stiffness. Conclusions: This study provides a genetic basis for the causal relationship between elevated iron status and increased arterial stiffness, suggesting the important role of micronutrients in the disease process.

Source: Reviews in Cardiovascular Medicine

DOI: 10.31083/rcm27920