Table_1_Association between copper intake and essential hypertension: dual evidence from Mendelian randomization analysis and the NHANES database.docx

BackgroundAlthough previous studies have identified an association between trace elements and essential hypertension, the specific trace elements involved and the mechanisms of their association remain unclear. This study aimed to elucidate the relationship between various human trace elements and essential hypertension, thereby addressing existing gaps in the research.
MethodsThis study employed two-sample, multivariate, and inverse Mendelian randomization (MR) analyses to investigate the causal relationship between 15 human trace elements as exposure factors and essential hypertension as the outcome. The analysis revealed a statistically significant association between copper intake and essential hypertension. Further validation was conducted using logistic regression models based on data from the National Health and Nutrition Examination Survey (NHANES).
ResultsEighteen trace elements were initially identified through searches in the GWAS database and PubMed. After screening, 15 trace elements were selected as potential exposure factors. MR analysis, utilizing the 2021 genome-wide dataset for essential hypertension, identified copper as a risk factor, showing a positive association with hypertension. Subsequent logistic regression analyses based on NHANES data further confirmed a significant association between dietary copper intake and the risk of essential hypertension, except for the 0.80–1.08 mg/d group in model 3 (p < 0.05). Restricted cubic spline (RCS) analysis indicated a nonlinear relationship between copper intake and the risk of developing essential hypertension.
ConclusionThis study demonstrates a significant association between copper intake and the development of essential hypertension. The findings suggest that higher copper intake is linked to an increased risk of hypertension, underscoring the need to monitor copper intake levels in the prevention and management of this condition.

研究背景：尽管既往研究已证实微量元素与原发性高血压之间存在关联，但所涉及的具体微量元素及其关联机制仍未明确。本研究旨在阐明人体多种微量元素与原发性高血压的关联，以期填补当前该领域的研究空白。
研究方法：本研究采用两样本、多变量及逆孟德尔随机化（Mendelian Randomization, MR）分析，以15种人体微量元素作为暴露因素，以原发性高血压作为结局指标，探究二者间的因果关系。分析结果显示，铜摄入量与原发性高血压之间存在统计学显著性关联。本研究还基于美国国家健康与营养调查（National Health and Nutrition Examination Survey, NHANES）的数据，通过logistic回归模型开展了进一步验证。
研究结果：本研究首先在全基因组关联研究（Genome-Wide Association Study, GWAS）数据库及PubMed中检索得到18种微量元素，经筛选后选取15种作为潜在暴露因素。利用2021年原发性高血压全基因组数据集开展MR分析，结果表明铜为高血压的危险因素，二者呈正相关。后续基于NHANES数据的logistic回归分析进一步证实，除模型3中0.80–1.08 mg/d组外，膳食铜摄入量与原发性高血压发病风险间存在显著关联（p < 0.05）。限制性立方样条（Restricted Cubic Spline, RCS）分析显示，铜摄入量与原发性高血压发病风险之间存在非线性关联。
研究结论：本研究证实铜摄入量与原发性高血压的发生存在显著关联。研究结果表明，更高的铜摄入量与高血压发病风险升高相关，这提示在该疾病的预防与管理中，监测铜摄入量水平具有重要意义。