Serum Ferritin Concentrations Are Not Modified in the Acute Phase of Ischemic Stroke
1998; Lippincott Williams & Wilkins; Volume: 29; Issue: 1 Linguagem: Inglês
10.1161/01.str.29.1.258
ISSN1524-4628
AutoresA. Armengou, Antoni Dávalos, José Manuel Fernández‐Real, José Castillo,
Tópico(s)Folate and B Vitamins Research
ResumoHomeStrokeVol. 29, No. 1Serum Ferritin Concentrations Are Not Modified in the Acute Phase of Ischemic Stroke Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherPDF/EPUBSerum Ferritin Concentrations Are Not Modified in the Acute Phase of Ischemic Stroke Arola Armengou and Antoni Dávalos José Manuel Fernandez-Real José Castillo Arola ArmengouArola Armengou Section of Neurology, Hospital Universitari Doctor Josep Trueta, Girona, Spain and Antoni DávalosAntoni Dávalos Section of Neurology, Hospital Universitari Doctor Josep Trueta, Girona, Spain José Manuel Fernandez-RealJosé Manuel Fernandez-Real Section of Endocrinology, Hospital Universitari Doctor Josep Trueta, Girona, Spain José CastilloJosé Castillo Service of Neurology, Hospital Xeral de Galicia, Santiago de Compostela, Spain Originally published1 Jan 1998https://doi.org/10.1161/01.STR.29.1.258Stroke. 1998;29:258–260To the Editor: Three major molecular events in brain damage from cerebrovascular occlusion are at present the focus of interest: calcium overload, excessive acidosis, and enhanced production of free radicals. Free radicals are generated in increased amounts under ischemic conditions and react with and damage proteins, nucleic acids, and membrane lipids, disrupting cellular integrity.1 This oxygen radical activity is especially intense during reperfusion after sustained ischemia. The generation of radical hydroxyl, the most toxic and reactive of free radicals, is catalyzed by ferrous iron released from intracellular stores during ischemia; thus, the sensitivity of neurons to oxidative stress depends on the availability of iron in the ischemic focus.23 Iron is released from large transport proteins, particularly from ferritin, which accounts for one third to three quarters of brain iron.4 In the absence of inflammation, cancer, and infectious diseases, the serum concentration of ferritin is thought to be directly proportional to tissue iron stores and can be used to assess their size.5Despite the theoretical importance of iron in oxidative brain injury, very little direct evidence exists to implicate iron in stroke. In experimental models, iron depletion or chelation reduces ischemia-reperfusion–induced edema and metabolic failure.67 We found in 67 patients with acute ischemic stroke that high serum ferritin levels within the first 48 hours after stroke onset were associated with a poor prognosis, independent of the stress response.8 Using the same protocol, we have recently reproduced these results in a different and larger series of 103 patients (A. Dávalos, personal communication, European Stroke Conference, Amsterdam, the Netherlands, 1997). Median serum ferritin concentrations were 383 μg/L (quartiles, 158 and 442) in 40 patients with poor outcome and 218 μg/L (quartiles, 129 and 345) in 63 with good outcome (P=.004). Because ferritin concentrations in both studies were measured only once, usually several hours after stroke onset, an early increase due to the acute-phase response was not completely ruled out. The aim of this study was to demonstrate that serum ferritin concentrations were not modified during the acute phase (5 days) of ischemic stroke and that they were not related to stress and inflammatory reactions.We studied prospectively a group of 34 consecutive patients (mean age 69±8 years; 14 males and 20 females) with an acute ischemic stroke of <8 hours in duration. Blood samples were collected at admission (mean time from stroke onset, 4.9±1.4 hours); at 12, 24, and 48 hours; and at day 5 from the onset of symptoms. Laboratory parameters measured for the purpose of this study were serum ferritin, cortisol, and C-reactive protein. In addition, leucocyte count and plasma fibrinogen were determined in the first blood sample. Diabetes was recorded in 9 patients, hypertension in 16, atrial fibrillation in 12, and ischemic heart disease in 2. The type of stroke was large-artery atherothrombotic infarct in 12 patients, cardioembolic in 11, lacunar in 6, and of unknown origin in 5. The mean Canadian Stroke Scale score at admission was 5.5±2.7. One patient died on the second day of hospitalization, and 6 patients had infectious or inflammatory diseases during the 5-day study period.Comparisons for paired measures (Wilcoxon rank test) showed no statistical differences between the concentrations of ferritin at admission and those obtained at each time interval during the first 48 hours, whereas cortisol values decreased significantly and C-reactive protein showed a moderate increase after the first 24 hours from stroke onset (Figure). In those patients with infectious or inflammatory diseases, ferritin concentrations were stable during the early acute phase but increased significantly after 24 hours from stroke onset, as did C-reactive protein. Ferritin values did not correlate with leucocyte count and fibrinogen concentrations at inclusion (Spearman coefficients of .083 and .19, respectively; P=NS). The correlations between ferritin values and cortisol and C-reactive protein values of each sample obtained during the study period were not significant (coefficients, <0.25; P=NS).Our results confirm that serum ferritin concentrations are not associated with the stress reaction and the acute phase response. The nonsignificant rise in serum ferritin during the first 2 days after stroke is of insufficient magnitude to explain the large difference in ferritin levels between the patients with good prognoses and those with bad prognoses reported by our group.8 These findings suggest that serum ferritin can provide a reliable index of iron stores in acute stroke patients without infectious or inflammatory diseases. Therefore, the association between increased concentrations of ferritin and poor outcome found in our previous investigations could be attributed to a potentially increased availability of iron in the ischemic area. A later increase of ferritin in some patients after the second day was consistent with stroke comorbidity. However, serum ferritin may be primarily an indicator of other vascular risk factors themselves related to stroke prognosis. Iron overload may elevate the risk of atherosclerotic diseases by promoting the oxidation of LDL cholesterol.9 High serum ferritin concentrations in the early acute phase of stroke could also result from inflammatory changes or infections preceding cerebral ischemia that have been recognized as risk factors for stroke and transient ischemic attack.10 Nevertheless, in this study the lack of association of serum ferritin on admission with other analytical parameters such as leucocyte count, fibrinogen, and C-reactive protein, which have been all related to previous chronic inflammation in patients with ischemic vascular diseases,11 makes this mechanism improbable. Serum ferritin determination should be included in future investigations on prognostic factors in acute ischemic stroke.Download figureDownload PowerPoint Figure 1. Median values and quartiles of serum ferritin (top panel), plasmatic cortisol (middle), and C-reactive protein (bottom) concentrations at each interval from symptom onset in 34 patients with acute ischemic stroke. Numbers indicate probability values (Wilcoxon rank test) of the comparisons between the concentrations of laboratory parameters at admission and those obtained at each time interval. References 1 Schmidley JW. Free radicals in central nervous system ischemia. Stroke..1990; 25:7-12.Google Scholar2 Reif DW. Ferritin as a source of iron for oxidative damage. Free Radic Biol Med..1992; 12:417-427.CrossrefMedlineGoogle Scholar3 Chan PH. Role of oxidants in ischemic brain damage. Stroke..1996; 27:1124-1129.CrossrefMedlineGoogle Scholar4 Connor JR. Cellular and regional maintenance of iron homeostasis in the brain: normal and diseased states. In: Riederer P, Youdin MBH, eds. Iron in Central Nervous System Disorders. Springer-Verlag/Wien, New York, NY: 1993:1-18.Google Scholar5 Salonen JT. The role of iron as a cardiovascular risk factor. Curr Opin Lipidol..1993; 4:277-282.CrossrefGoogle Scholar6 Patt A, Horesh IR, Berger EM, Harken AH, Repine JE. Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. J Pediatr Surg..1990; 25:224-228.CrossrefMedlineGoogle Scholar7 Davis S, Helfaer MA, Traystman RJ, Hurn PD. Parallel antioxidant and antiexcitotoxic therapy improves outcome after incomplete global cerebral ischemia in dogs. Stroke..1997; 28:198-205.CrossrefMedlineGoogle Scholar8 Dávalos A, Fernandez-Real JM, Ricart W, Soler S, Molins A, Planas E, Genís D. Iron-related damage in acute ischemic stroke. Stroke..1994; 25:1543-1546.CrossrefMedlineGoogle Scholar9 Salonen JK, Nyssönen K, Korpela H, Tuomilehto J, Seppänen R, Salonen R. High stored iron levels are associated with excess risk of myocardial infarction in eastern Finnish men. Circulation..1992; 86:803-811.CrossrefMedlineGoogle Scholar10 Grau A, Buggle F, Heindl S, Steichen-Wiehn C, Banerjee T, Maiwald M, Rohlfs M, Suhr H, Fiehn W, Becher H, Hacke W. Recent infection as a risk factor for cerebrovascular ischemia. Stroke..1995; 26:373-379.CrossrefMedlineGoogle Scholar11 Grau A, Buggle F, Becher H, Werle E, Hacke W. The association of leukocyte count, fibrinogen, and C-reactive protein with vascular risk factors and ischemic vascular diseases. Thromb. Res..1996; 82:245-255.CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. 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Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetailsCited By Rajendran S, Periyasamy S, Manjuladevi M and George N (2019)(2020) Evaluation of Serum Ferritin as a Prognostic Marker in Acute Hemorrhagic Stroke, Journal of Neurosciences in Rural Practice, 10.1055/s-0039-1700597, 11, (72-77) Kusvuran Ozkan A, Umit Yemisci O, Nur Saracgil Cosar S, Oztop P and Turhan N (2015) Can High-Sensitivity C-Reactive Protein and Ferritin Predict Functional Outcome in Acute Ischemic Stroke? A Prospective Study, Topics in Stroke Rehabilitation, 10.1310/tsr2006-528, 20:6, (528-536), Online publication date: 1-Nov-2013. Chakraborty B, Vishnoi G, Goswami B, Gowda S, Chowdhury D and Agarwal S (2013) Lipoprotein(a), Ferritin, and Albumin in Acute Phase Reaction Predicts Severity and Mortality of Acute Ischemic Stroke in North Indian Patients, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2012.10.013, 22:7, (e159-e167), Online publication date: 1-Oct-2013. García-Yébenes I, Sobrado M, Moraga A, Zarruk J, Romera V, Pradillo J, Perez de la Ossa N, Moro M, Dávalos A and Lizasoain I (2012) Iron overload, measured as serum ferritin, increases brain damage induced by focal ischemia and early reperfusion, Neurochemistry International, 10.1016/j.neuint.2012.09.014, 61:8, (1364-1369), Online publication date: 1-Dec-2012. Choi K, Park M, Kim J, Nam T, Choi S, Kim B, Kim M and Cho K (2011) The serum ferritin level is an important predictor of hemorrhagic transformation in acute ischaemic stroke, European Journal of Neurology, 10.1111/j.1468-1331.2011.03564.x, 19:4, (570-577), Online publication date: 1-Apr-2012. Üstündağ M, Orak M, Güloğlu C, Öztürk E, Tamam Y and Kale E (2017) The Role of Serum Ferritin, Pro-Brain Natriuretic Peptide and Homocysteine Levels in Determining Ischaemic Stroke Subtype, Severity and Mortality, Hong Kong Journal of Emergency Medicine, 10.1177/102490791001700103, 17:1, (13-21), Online publication date: 1-Jan-2010. Erdemoglu A and Ozbakir S (2002) Serum ferritin levels and early prognosis of stroke, European Journal of Neurology, 10.1046/j.1468-1331.2002.00472.x, 9:6, (633-637), Online publication date: 1-Nov-2002. Dávalos A and Castillo J (2001) Progressing Stroke Current Review of Cerebrovascular Disease, 10.1007/978-1-4684-0001-4_16, (169-181), . January 1998Vol 29, Issue 1 Advertisement Article InformationMetrics Copyright © 1998 by American Heart Associationhttps://doi.org/10.1161/01.STR.29.1.258 Originally publishedJanuary 1, 1998 PDF download Advertisement
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