Supplementary Material for: Differences in iron kinetics during cardiac load between patients with atrial fibrillation and those with sinus rhythm

Introduction: The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all elderly individuals develop AF. Moreover, risk factors such as hypertension and diabetes do not always lead to AF, even in severe conditions such as pneumonia. We aimed to examine iron kinetics, including ferritin, in patients with AF and individuals in normal sinus rhythm (NSR) using peripheral blood samples.
Methods: This case-control study included 178atients who visited the outpatient clinic of a cardiovascular and arrhythmia specialist at the National Center for Geriatrics and Gerontology between August and October 2023. Patients with missing iron-related blood tests and those with pacemaker implantation were excluded. Iron parameters (ferritin, free iron, transferrin saturation) were compared between AF (n = 53) and NSR (n = 125) groups.
Results: The AF group had higher Log brain natriuretic peptide (BNP) levels, indicating increased cardiac load (AF 2.18 vs NSR 1.53). However, there were no significant differences in iron parameters between the AF and NSR groups. After matching for age, sex, and coronary artery disease, the AF group showed an increasing trend in ferritin and a decreasing trend in free iron with BNP elevation, suggesting chronic inflammation. In contrast, the NSR group showed no significant changes in iron parameters with BNP elevation.
Conclusion: Patients with AF are more likely to have elevated ferritin levels and decreased free iron levels during cardiac overload. Thus, they are more likely to present with chronic inflammation associated with cardiac overload in AF. Future studies should investigate the mechanisms underlying this phenomenon and its implications for AF treatment.

引言：心房颤动（atrial fibrillation, AF）的患病率随年龄增长而升高。尽管多数房颤病例由肺静脉附近的异常电冲动引发，但并非所有老年人都会罹患房颤。此外，诸如高血压、糖尿病等危险因素即便在肺炎等严重病症下，也并非总会导致房颤发生。本研究旨在通过外周血样本，对比心房颤动患者与正常窦性心律（normal sinus rhythm, NSR）个体的铁代谢动力学指标，包括铁蛋白。
方法：本病例对照研究纳入了2023年8月至10月期间，在日本国立老年医学与老年病研究中心心血管与心律失常专科门诊就诊的178例患者。排除了铁相关血液检测缺失及已植入心脏起搏器的患者。将心房颤动组（n=53）与正常窦性心律组（n=125）的铁代谢参数（铁蛋白、游离铁、转铁蛋白饱和度）进行对比。
结果：心房颤动组的对数转换脑钠肽（brain natriuretic peptide, BNP）水平更高，提示心脏负荷增加（心房颤动组为2.18，正常窦性心律组为1.53）。然而，两组间的铁代谢参数并无显著差异。在匹配年龄、性别与冠状动脉疾病情况后，心房颤动组随BNP水平升高，铁蛋白呈上升趋势，游离铁呈下降趋势，该现象提示存在慢性炎症。与之相反，正常窦性心律组的铁代谢参数未随BNP水平升高出现显著变化。
结论：心房颤动患者在心脏负荷增加时，更易出现铁蛋白水平升高与游离铁水平降低的情况，即更易伴随与心脏负荷相关的慢性炎症。未来的研究应进一步阐明该现象的潜在机制及其在心房颤动治疗中的应用价值。