BACKGROUND:This study focused on circulating plasma protein profiles to identify mediators of hypertension-driven myocardial remodeling and heart failure.METHODS:A Mendelian randomization design was used to investigate the causal impact of systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure on 82 cardiac magnetic resonance traits and heart failure risk. Mediation analyses were also conducted to identify potential plasma proteins mediating these effects.RESULTS:Genetically proxied higher SBP, DBP, and pulse pressure were causally associated with increased left ventricular myocardial mass and alterations in global myocardial wall thickness at end diastole. Elevated SBP and DBP were linked to increased regional myocardial radial strain of the left ventricle (basal anterior, mid, and apical walls), while higher SBP was associated with reduced circumferential strain in specific left ventricular segments (apical, mid-anteroseptal, mid-inferoseptal, and mid-inferolateral walls). Specific plasma proteins mediated the impact of blood pressure on cardiac remodeling, with FGF5 (fibroblast growth factor 5) contributing 2.96% (P=0.024) and 4.15% (P=0.046) to the total effect of SBP and DBP on myocardial wall thickness at end diastole in the apical anterior segment and leptin explaining 15.21% (P=0.042) and 23.24% (P=0.022) of the total effect of SBP and DBP on radial strain in the mid-anteroseptal segment. Additionally, FGF5 was the only mediator, explaining 4.19% (P=0.013) and 4.54% (P=0.032) of the total effect of SBP and DBP on heart failure susceptibility.CONCLUSIONS:This mediation Mendelian randomization study provides evidence supporting specific circulating plasma proteins as mediators of hypertension-driven cardiac remodeling and heart failure.

中文翻译：

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循环血浆蛋白作为高血压驱动的心脏重构调节剂的鉴定：孟德尔随机化研究

背景：本研究重点关注循环血浆蛋白谱，以确定高血压驱动的心肌重塑和心力衰竭的介质。方法：采用孟德尔随机化设计来研究收缩压（SBP）、舒张压（DBP）的因果影响和脉压对 82 种心脏磁共振特征和心力衰竭风险的影响。还进行了中介分析，以确定介导这些影响的潜在血浆蛋白。结果：基因代理的较高收缩压、舒张压和脉压与左心室心肌质量增加和舒张末期心肌壁厚度改变存在因果关系。收缩压和舒张压升高与左心室（基底前壁、中壁和心尖壁）局部心肌径向应变增加有关，而较高的收缩压与特定左心室节段（心尖、中前间壁、中前壁）周向应变减少相关。下间隔和中下侧壁）。特定血浆蛋白介导血压对心脏重塑的影响，其中 FGF5（成纤维细胞生长因子 5）对 SBP 和 DBP 对心肌壁厚度的总影响分别贡献 2.96% ( P = 0.024) 和 4.15% ( P = 0.046)。心尖前段舒张末期和瘦素解释了SBP 和 DBP 对中前间段径向应变的总影响的15.21% ( P = 0.042) 和 23.24% ( P = 0.022)。此外，FGF5 是唯一的中介因素，解释了 SBP 和 DBP 对心力衰竭易感性总影响的 4.19%（P = 0.013）和 4.54%（P = 0.032）。 结论：这项中介孟德尔随机化研究提供了支持特定循环血浆的证据蛋白质作为高血压驱动的心脏重塑和心力衰竭的介质。