The association between ferritin levels and all-cause mortality in stroke patients

 Who approved this useless research that predicts mortality rather than prevents it? They need to be fired!

The association between ferritin levels and all-cause mortality in stroke patients

Xuefen Xia¹Jiongjiong Liu²Wenqiang Fang¹Zhibo Chen¹Jie Wang^3*Huiqin Xu^1*

• ¹Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
• ²Department of General Practice, Fuyang Hospital Affiliated to Anhui Medical University, Anhui, China
• ³Department of Endocrinology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Purpose: The purpose of study was to describe the association between ferritin and all-cause mortality of cases with stroke.

Methods: Clinical data derived from Multiparameter Intelligent Monitoring in Intensive Care were analyzed. The primary endpoint was 30-day mortality. The potential prognostic roles of Ferritin L were analyzed by Cox proportional hazard models. The independent prognostic roles of Ferritin L in the cases were analyzed by smooth curve fitting.

Results: Concerning 30-day mortality, the HR (95% CI) for a high Ferritin (≥373) was 1.925 (1.298, 2.854; p = 0.00113), compared to a low ferritin (< 373). After adjusting for multiple confounders, the HR (95% CI) for a high Ferritin (≥373) was 1.782 (1.126, 2.820; p = 0.01367), compared to a low Ferritin (< 373). A non-linear association between Ferritin and 30-day mortality was found. Using recursive algorithm and two-piecewise linear regression model, inflection point (IP) was calculated, which was 2,204. On the left side of the IP, there was a positive relationship between Ferritin and 30-day mortality, and the effect size, 95% CI and p value were 1.0006 (1.0004, 1.0009) p < 0.0001, respectively. On the right of the IP, the effect size, 95% CI and p value were 1.0000 (1.0000, 1.0000) and 0.3107, respectively.

Conclusion: Ferritin was associated with increased risk of stroke; it is important to further examine the association if the increased uric acid would increase the outcome of stroke in a longitudinal study. The non-linear relationship between Ferritin and all-cause mortality of stroke was observed. Ferritin was a risk factor for the outcome of stroke when ferritin was <2204.

1 Introduction

Stroke, a neurological deficit originating from cerebrovascular causes, disrupts blood supply to part of the brain, potentially inducing irreversible damage to deprived neural tissues and consequently triggering substantial morbidity and mortality worldwide (1–3). With various subtypes, including ischemic and hemorrhagic strokes, each presenting unique pathophysiology, risk factors, and outcomes, stroke management demands rigorous attention to detail, a comprehension of its multifaceted nature, and often, a patient-centric approach to care (4). While acute phase interventions, both medical and/or surgical, followed by rehabilitative strategies, remain fundamental to stroke management, a prudent understanding and investigation of potential prognostic markers are pivotal to interpret, forecast, and possibly enhance patient outcomes (3–5).

Ferritin, a cellular protein that binds and sequesters iron, is traditionally recognized as an indicator of iron stores within the body (6, 7). Elevated serum ferritin levels, aside from implications in iron metabolism disorders, have also been acknowledged as an acute-phase reactant, often elevating in situations of systemic inflammation, cellular injury, and specific disease states (8). Within cardiovascular diseases, elevated ferritin levels have been associated with adverse outcomes, highlighting its potential utility as a prognostic marker (9). Furthermore, emerging data insinuate that ferritin, through its involvement in iron metabolism and its capacity to induce oxidative stress, might participate in the pathophysiological cascade following ischemic cell death and in propagating secondary injury mechanisms post-stroke. Nevertheless, the explicit association between ferritin levels and outcomes in stroke patients warrants further elucidation. While stroke instigates a complex interplay of inflammatory, oxidative, and neurodegenerative processes, defining the role of ferritin—both as a marker and a participant in this cascade—requires meticulous investigation (10, 11). Given the pathophysiological complexity and heterogeneity among stroke patients, it is imperative to discern whether ferritin levels maintain a consistent, independent association with outcomes or simply reflect the inflammatory and oxidative processes that prevail following cerebral ischemia or hemorrhage (12, 13).

This study commences an exploration into the association between serum ferritin levels and all-cause mortality in stroke patients, delving into the complexities of stroke subtypes and coexisting variables that could potentially influence this relationship. By unraveling these associations, we aim to enhance our understanding of stroke pathophysiology, potentially facilitating the development of novel prognostic and therapeutic strategies aimed at mitigating the profound impact of this formidable neurological challenge. In this study, we utilized real-world data obtained from the latest Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) database to assess the association between ferritin and stroke patient outcomes, adjusting for various potential confounders.

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