射血分数保留人群中全身铁参数与左心室结构和功能的相互作用：一项两样本双向孟德尔随机化研究
Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population: a two-sample bidirectional Mendelian randomization study.
作者信息
Ma Xiong-Bin, Liu Yong-Ming, Lv Yan-Lin, Qian Lin
机构信息
The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China.
Geriatric Cardiovascular Department and Gansu Clinical Research Center for Geriatric Diseases, First Hospital of Lanzhou University, Gansu, China.
出版信息
J Geriatr Cardiol. 2024 Jan 28;21(1):64-80. doi: 10.26599/1671-5411.2024.01.006.
BACKGROUND
Left ventricular (LV) remodeling and diastolic function in people with heart failure (HF) are correlated with iron status; however, the causality is uncertain. This Mendelian randomization (MR) study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction population.
METHODS
Transferrin saturation (TSAT), total iron binding capacity (TIBC), and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association studies. Individuals without myocardial infarction history, HF, or LV ejection fraction (LVEF) < 50% ( = 16,923) in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome dataset. The dataset included LV end-diastolic volume, LV end-systolic volume, LV mass (LVM), and LVM-to-end-diastolic volume ratio (LVMVR). We used a two-sample bidirectional MR study with inverse variance weighting (IVW) as the primary analysis method and estimation methods using different algorithms to improve the robustness of the results.
RESULTS
In the IVW analysis, one standard deviation (SD) increased in TSAT significantly correlated with decreased LVMVR (β = -0.1365; 95% confidence interval [CI]: -0.2092 to -0.0638; = 0.0002) after Bonferroni adjustment. Conversely, no significant relationships were observed between other iron and LV parameters. After Bonferroni correction, reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT (β = -0.0699; 95% CI: -0.1087 to -0.0311; = 0.0004). No heterogeneity or pleiotropic effects evidence was observed in the analysis.
CONCLUSIONS
We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.
背景
心力衰竭（HF）患者的左心室（LV）重构和舒张功能与铁状态相关；然而，因果关系尚不确定。这项孟德尔随机化（MR）研究调查了射血分数保留人群中全身铁参数与LV结构和功能之间的双向因果关系。
方法
从公开的全基因组关联研究的荟萃分析中提取转铁蛋白饱和度（TSAT）、总铁结合力（TIBC）以及血清铁和铁蛋白水平作为铁参数的工具变量。英国生物银行心血管磁共振成像研究中无心肌梗死病史、HF或左心室射血分数（LVEF）<50%（n = 16,923）的个体构成结局数据集。该数据集包括左心室舒张末期容积、左心室收缩末期容积、左心室质量（LVM）以及LVM与舒张末期容积之比（LVMVR）。我们采用双样本双向MR研究，以逆方差加权（IVW）作为主要分析方法，并使用不同算法的估计方法来提高结果的稳健性。
结果
在IVW分析中，经Bonferroni校正后，TSAT增加一个标准差（SD）与LVMVR降低显著相关（β = -0.1365；95%置信区间[CI]：-0.2092至-0.0638；P = 0.0002）。相反，未观察到其他铁参数与LV参数之间存在显著关系。经Bonferroni校正后，反向MR分析显示LVEF增加一个SD与TSAT降低显著相关（β = -0.0699；95%CI：-0.1087至-0.0311；P = 0.0004）。分析中未观察到异质性或多效性效应的证据。
结论
我们在射血分数保留人群中证明了TSAT与LV重构和功能之间存在因果关系。
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