Low Serum Ferritin Might Predict Incident Heart Failure: But Why and Is It Clinically Useful?
Low Serum Ferritin Might Predict Incident Heart Failure: But Why and Is It Clinically Useful?
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低血清铁蛋白可能预测心力衰竭的发生：但为什么以及它在临床上有用吗？
DOI：
10.1016/j.jchf.2023.12.012
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Cleland JGF
中科院分区：
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作者：
Cleland JGF
ARIC(社区动脉粥样硬化风险)研究是一项正在进行的纵向队列研究，从1987年到1989年期间，从美国的4个中心招募了15,792名年龄在45岁-之间的社区成年人。1先前对1,063名参与者(平均年龄：53岁；62%女性)进行的基线测量分析发现，与其他人一样，血清铁蛋白与新诊断心力衰竭的风险之间呈U型关系，新诊断心力衰竭的风险被定义为任何提及(原发的、继发的或偶然的)出院或死亡记录，1血清铁蛋白为121μg/L时的风险最低点。在第五次随访(2011-2013年)中采集样本的女性(56%)现在报告了血清铁蛋白与心力衰竭风险之间的线性负相关关系，主要是心力衰竭和保留的左心室射血分数。1这两份报告之间差异的原因可能包括年龄的差异(因此疾病的患病率)、随访时间的差异(21年对7年)、心力衰竭诊断的变化、引入裁决、事件的数量(144vs293)、应用的统计方法，或者铁蛋白检测的差异。血清铁蛋白降低50%(测量单位不可用)的心力衰竭风险仅增加20%(每1000名患者发生2-3次事件--年随访)，这可能不是心力衰竭预防策略的临床有用补充，但尽管如此，铁状态和结果之间的关系仍然具有科学意义。铁对大多数生命形式都是剧毒的，但少量是必不可少的。2生物系统已经进化，以防止过量铁的吸收，并安全地储存少量铁。铁蛋白存在于每一种细胞类型中，形成一个由多个轻链和重链组成的蛋白质纳米笼子，这些轻链和重链捕获并存储处于非反应性但容易获得的状态的铁。轻链的产生受细胞内铁量的调节。重链的产生既受铁的调节，也受促炎蛋白肿瘤坏死因子(TNF)的调节。在健康状态下，只有一小部分铁耗竭的铁蛋白被分泌到血浆中，而且它似乎几乎完全来自巨噬细胞，巨噬细胞主要通过消化衰老的红细胞来获得铁。然而，在心血管疾病患者中，肿瘤坏死因子的分泌增加增加了铁蛋白重链和海普西丁的产生，这阻止了细胞输出铁，导致细胞内铁积累，从而增加了铁蛋白轻链和重链。细胞内铁蛋白的增加会导致其释放增加。因此，低血清铁蛋白需要低水平的细胞内铁和低丰度的肿瘤坏死因子。对于慢性病患者，血清铁蛋白和肌钙蛋白一样，可能是一种
The ARIC (Atherosclerosis Risk In Communities) study is an ongoing longitudinal cohort that enrolled 15,792 communitydwelling adults aged 45-64 years from 4 centers in the United States between 1987 and 1989. 1 A previous analysis using baseline measurements on a subset of 1,063 participants (mean age: 53 years; 62% women) found, as have others, a U-shaped relationship between serum ferritin and the risk of a new diagnosis of heart failure defined as any mention (primary, secondary, or incidental) on hospital discharge or death records, 1 with a nadir of risk at a serum ferritin of 121 μg/L. A new analysis from ARIC, including 3,472 participants (mean age: 74 years; 56% women) with samples taken at the fifth follow-up visit (2011-2013) now reports a linear inverse relationship between serum ferritin and the risk of heart failure, predominantly with heart failure and preserved left ventricular ejection fraction. 1 Explanations for discrepancies between these 2 reports might include differences in age (and therefore prevalence of disease), differences in duration of follow-up (21 years vs 7 years), changes in what constitutes a diagnosis of heart failure, introduction of adjudication, the number of events (144 vs 293), statistical methods applied, or differences in ferritin assays. The risk of heart failure for a 50% lower serum ferritin (measurement units not available) increased by only 20%(2-3 events per 1,000 patient-years of follow-up), which is probably not a clinically useful addition to a heart failure prevention strategy, but nonetheless the relationship between iron status and outcome remains of scientific interest.Iron is extremely toxic to most forms of life but in small amounts is essential. 2 Biological systems have evolved to prevent the absorption of excess iron and to store small amounts safely. Ferritin, present in every cell type, forms a protein nanocage composed of multiple light and heavy chains that trap and store iron in a nonreactive but readily available state. Production of light chains is regulated by the amount of intracellular iron. Production of heavy chains is regulated both by iron and by the pro-inflammatory protein tumor necrosis factor (TNF). In health, only a small amount of iron-depleted ferritin is secreted into the plasma, and it seems almost entirely derived from macrophages, which acquire iron mainly by digesting senescent erythrocytes. 2 However, in patients with cardiovascular disease, increased secretion of TNF increases the production of ferritin heavy chains and of hepcidin, which prevents cells from exporting iron, leading to intracellular iron accumulation, thereby increasing both ferritin light and heavy chains. Increases in intracellular ferritin then lead to its increased release. Accordingly, a low serum ferritin requires low levels of both intracellular iron and low abundance of TNF. For patients with chronic disease, serum ferritin, like troponin, may be a