Qiao Weishen, Liu Qi, Ding Hongyu, Wang Gang, Sun Yufei, Yao Zhibo, Huang Xingtao, Wang Xuedong, Fu Chao, Hou Jingbo
Department of Cardiology Organization, The Second Affiliated Hospital of Harbin Medical University, 150001 Harbin, Heilongjiang, China.
Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, 150001 Harbin, Heilongjiang, China.
Rev Cardiovasc Med. 2025 May 20;26(5):27920. doi: 10.31083/RCM27920. eCollection 2025 May.
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.
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.
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], = 1.87 × 10) [false discovery rate, FDR], ferritin (β = 0.143, 95% CI [0.050 to 0.235], = 8.28 × 10), and transferrin saturation (β = 0.053, 95% CI [0.025 to 0.080], = 1.29 × 10) 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.
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.
先前关于铁状态与动脉僵硬度之间关系的研究有限，因果关系仍不明确。然而，了解这些联系对于改善动脉僵硬度的预防和管理至关重要。因此，本研究旨在使用孟德尔随机化（MR）方法研究铁状态和其他微量营养素对动脉僵硬度风险的影响。
利用来自欧洲人群的全基因组关联研究（GWAS）数据进行MR分析，以研究各种营养素（铁等）与动脉僵硬度指数之间的因果关系。我们选择随机效应逆方差加权（IVW）方法进行主要分析，并进行了多次敏感性测试以确保准确性。
本研究发现，基因预测的高水平血清铁（β = 0.069，95%置信区间[CI][0.031至0.107]， = 1.87×10）[假发现率，FDR]、铁蛋白（β = 0.143，95%CI[0.050至0.235]， = 8.28×10）和转铁蛋白饱和度（β = 0.053，95%CI[0.025至0.080]， = 1.29×10）对动脉僵硬度指数有因果效应。没有反向因果关系的证据。在调整潜在混杂因素后，多变量MR分析得出的关联仍然显著。锌和胡萝卜素水平可能与动脉僵硬度呈负相关。
本研究为铁状态升高与动脉僵硬度增加之间的因果关系提供了遗传基础，表明微量营养素在疾病过程中的重要作用。
