Published online before print October 7, 2004, doi: 10.1161/01.STR.0000145487.89910.12
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(Stroke. 2004;35:2435.)
© 2004 American Heart Association, Inc.
Letters to the Editor |
Serum Albumin Level as a Predictor of Ischemic Stroke Outcome
Divison of Neurology, Department of Medicine, National University Hospital, Singapore
To the Editor:
We read with great interest the recent article by Dr Dziedzic et al1 on the relationship between serum albumin level and ischemic stroke outcome. Even though low serum albumin has been associated with an increased incidence of stroke in epidemiologic studies,2 a high serum albumin level in acute stroke patients was described, for the first time, to decrease the risk of poor outcome among hospitalized patients. The neuroprotective effects of endogenous albumin on the capillary microcirculation in the early reperfusion phase were proposed to explain the cellular mechanism of this association, and the role of exogenous albumin therapy in stroke recovery was briefly reviewed.
It is important to recognize the role of serum albumin as a marker of clinical outcomes in vascular disease. Apart from stroke, serum albumin has been associated with adverse vascular events in patients with cardiac3 and renal4 diseases. Among hospitalized patients, hypoalbuminemia was found to be associated with frequent hospitalizations, higher mortality, and re-admission,5 and an independent prognostic factor for all deaths among healthy middle-aged individuals in population studies.6 Serum albumin is regulated by factors influencing protein synthesis, breakdown, leakage to the extravascular space, and food intake. In clinical practice, serum albumin is often considered a marker of nutritional status and a negative phase protein that decreases in concentration during injury and sepsis.7
There has been conflicting evidence in the literature on albumin therapy in treating patients with hypoalbuminemia from an underlying vascular disease. Albumin has a molecular weight of about 66 kDa, thus preventing it from passing through the blood-brain barrier by diffusion or by carrier systems through these membranes. Local redistribution, crystalloid dilution, and changes in the metabolism of albumin, which result in ineffective delivery and concentration within the central nervous system, frustrate therapeutic interventions. In septic patients, albumin therapy was not associated with a rise in serum albumin. Instead, a fall in serum albumin was observed and this was hypothesized to be secondary to capillary leakage.8
Until these important questions on albumin therapy are answered in randomized controlled studies, therapeutic options in patients with hypoalbuminemia should be directed toward treating the underlying cause, avoiding or treating salt and water overload, instituting prompt medical and surgical treatment of inflammation and sepsis, and providing appropriate nutritional support to enhance recovery in patients with ischemic strokes.
References
- Dziedzic T, Slowik A, Szczudlik A. Serum albumin level as a predictor of ischemic stroke outcome. Stroke. 2004; 35: 156–158.
[Free Full Text] - Gillum RF, Ingram DD, Makuc DM. Relation between serum albumin concentration and stroke incidence and death: the NHANES I Epidemiologic Follow-up Study. Am J Epidemiol. 1994; 140: 876–888.
[Abstract/Free Full Text] - Schillinger M, Exner M, Mlekusch W, Amighi J, Sabeti S, Schlager O, Wagner O, Minar E. Serum albumin predicts cardiac adverse events in patients with advanced atherosclerosis-interrelation with traditional cardiovascular risk factors. Thromb Haemost. 2004; 91: 610–618.[Medline] [Order article via Infotrieve]
- Cooper BA, Penne EL, Bartlett LH, Pollock CA. Protein malnutrition and hypoalbuminemia as predictors of vascular events and mortality in ESRD. Am J Kidney Dis. 2004; 43: 61–66.[CrossRef][Medline] [Order article via Infotrieve]
- Herrmann FR, Saqfran C, Levkoff SE, Minaker KL. Serum albumin level on admission as a predictor of death, length of stay, and readmission. Arch Intern Med. 1992; 152: 125–130.[Abstract]
- Phillips A, Shaper AG, Whincup PH. Assocation between serum albumin and mortality from cardiovascular disease, cancer and other causes. Lancet. 1989; 2: 1434–1436.[CrossRef][Medline] [Order article via Infotrieve]
- Liao WS, Jefferson LS, Taylor JM. Changes in plasma albumin concentration, synthesis rate, and mRNA level during acute inflammation. Am J Physiol. 1986; C928–C934.
- Margarson MP, Soni NC. Changes in serum albumin concentration and volume expanding effects following a bolus of albumin 20% in septic patients. Br J Anaesth. 2004; 92: 821–826.
[Abstract/Free Full Text]
Department of Neurology, Collegium Medicum, Jagiellonian University, Krakow, Poland
Response:
We thank Dr Seet and colleagues for their thoughtful comments to our article. We agree that hypoalbuminemia appears to be a predictor of poor prognosis in different clinical settings and even in apparently healthy individuals.1 It is still unknown in which way hypoalbuminemia can impair the prognosis. The mechanisms responsible for this phenomenon are not limited to energy depletion only, but can be also related to impaired immune and endocrine response, as well as extracellular water expansion.2 On the other hand, experimental studies revealed a beneficial effect of albumin infusion in animal models of cerebral ischemia and it was suggested that this neuroprotective effect is mediated by multiple specific actions of albumin including antioxidative properties, influence on endothelial functions, and venular perfusion.3,4 Which of the above-mentioned mechanisms of albumin action are relevant to human stroke remains to be established.
Albumin belongs to negative acute phase proteins. In our study we measured albumin level within 36 hours after stroke onset. We can’t exclude that acute phase response accompanying ischemic stroke can to some degree decrease albumin level in this time period. Inflammatory reaction defined as C-reactive protein level was found to be the most pronounced 3 to 7days after stroke onset.5 Davalos et al found fall in albumin concentration between day 1 and day 7 of stroke (40.7±4.6 versus 39.5±5.3 g/L) with borderline statistical significance (P=0.05).6 Other authors observed significant decrease in albumin level 2 and 4 weeks after stroke onset and this phenomenon couldn’t be explained by acute phase reaction.7 Unfortunately there is a lack of studies investigating changes in serum albumin level during acute phase of stroke.
Could albumin infusion be beneficial in human stroke? We share some concerns of Dr Seet and colleagues that this form of the therapy could be ineffective. However, we think that promising results of animal studies warrant the attempt to conduct clinical trials. In our opinion, 2 issues can be addressed in clinical studies: first, if correction of hypoalbuminemia (if possible) can influence the stroke outcome; second, if albumin infusion in early stroke in patients with normoalbuminemia can be beneficial as shown in animal models.
References
- Phillips A, Shaper AG, Whincup PH. Association between serum albumin and mortality from cardiovascular disease, cancer, and other causes. Lancet. 1989; 2: 1434–1436.[CrossRef][Medline] [Order article via Infotrieve]
- Franch-Arcas G. The meaning of hypoalbuminaemia in clinical practice. Clin Nutr. 2001; 20: 265–269.[CrossRef][Medline] [Order article via Infotrieve]
- Belayev L, Pinard E, Nallet H, Seylaz J, Liu Y, Riyamongkol P, Zhao W, Busto R, Ginsberg MD. Albumin therapy of transient focal cerebral ischemia: in vivo analysis of dynamic microvascular responses. Stroke. 2002; 33: 1077–1084.
[Abstract/Free Full Text] - Belayev L, Liu Y, Zhao W, Busto R, Ginsberg MD. Human albumin therapy of acute ischemic stroke: marked neuroprotective efficacy at moderate doses and with a broad therapeutic window. Stroke. 2001; 32: 553–560.
[Abstract/Free Full Text] - Acalovschi D, Wiest T, Hartmann M, Farahmi M, Mansmann U, Auffarth GU, Grau AJ, Green FR, Grond-Ginsbach C, Schwaninger M. Multiple levels of regulation of the interleukin-6 system in stroke. Stroke. 2003; 34: 1864–1869.
[Abstract/Free Full Text] - Davalos A, Ricart W, Gonzalez-Huix F, Soler S, Marrugat J, Molins A, Suner R, Genis D. Effect of malnutrition after acute stroke on clinical outcome. Stroke. 1996; 27: 1028–1032.
[Abstract/Free Full Text] - Gariballa SE, Parker SG, Taub N, Castleden CM. Influence of nutritional status on clinical outcome after acute stroke. Am J Clin Nutr. 1998; 8: 275–281.
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