Hypoalbuminemia in Acute Ischemic Stroke Patients: Frequency and Correlates

ORIGINAL ARTICLE Hypoalbuminemia in acute ischemic stroke patients: frequency and correlates

T Dziedzic, J Pera, A Slowik, EA Gryz-Kurek, and A Szczudlik

Department of Neurology, Collegium Medicum, Jagiellonian University, Krakow, Poland

Objective: Hypoalbuminemia in acute stroke patients is associated with increased mortality and morbidity. The aim of our study was to determine the frequency and correlates of hypoalbuminemia in unselected cohort of patients with acute cerebral infarction. Design: Prospective study. Setting: University hospital. Subjects: Seven hundred and five consecutive ischemic stroke patients. Methods: Albumin and other serum protein fractions were measured within 36 h after stroke using electrophoresis. Results: Hypoalbuminemia defined as serum albumin level o35 g/l was found in 45.5% of patients. Serum albumin level correlates significantly with age (r ¼À0.13, Po0.01), Scandinavian Stroke Scale score (r ¼ 0.14, Po0.01), body temperature on admission (r ¼ 0.14, Po0.01), leukocyte count (r ¼À0.17, Po0.01), fasting glucose (r ¼À0.16, Po0.01), total cholesterol (r ¼ 0.14, Po0.01), a1-globulin (r ¼À0.48, Po0.01), a2-globulin (r ¼À0.49, Po0.01), b-globulin (r ¼À0.26, Po0.01) and g-globulin (r ¼À0.35, Po0.01). Conclusions: Hypoalbuminemia is a frequent finding in acute stroke patients and it is associated with more severe stroke and pro-inflammatory pattern of serum protein electrophoresis. European Journal of Clinical Nutrition (2007) 61, 1318–1322; doi:10.1038/sj.ejcn.1602643; published online 24 January 2007

Keywords: stroke; albumin; cerebral ischemia

Introduction The goal of our study was to determine the frequency and correlates of hypoalbuminemia in unselected cohort of acute Low serum albumin level is frequently found in hospitalized stroke patients. older persons. Hypoalbuminemia was reported in up to 19% of stroke patients (Davalos et al., 1996; Gariballa et al., 1998; Davis et al., 2004). Stroke patients with hypoalbuminemia Materials and methods at admission had increased risk of infective complications (Gariballa et al., 1998; Dziedzic et al., 2006), death (Gariballa This study was a part of the prospective study investigating et al., 1998; Davis et al., 2004) and poor functional outcome the influence of serum albumin on stroke outcome (Dziedzic (Davalos et al., 1996; Gariballa et al., 1998). et al., 2004). All patients admitted between June 2000 and April 2003 with a diagnosis of ischemic stroke were eligible for this study, regardless of age, stroke etiology and concomitant diseases. The inclusion criteria were (1) first- ever stroke and (2) admission delay of less than 24 h from Correspondence: Dr T Dziedzic, Department of Neurology, Collegium onset of symptoms. Patients with transient ischemic attack Medicum, Jagiellonian University, 31-503 Krako´w, ul. Botaniczna 3, Poland. E-mail: [email protected] were excluded from the study. Contributors: TD, JP, AS contributed to the study design. TD, JP, AS, EAG-K Arterial hypertension was diagnosed when its presence was contributed to the data collection. TD, JP, AS contributed to the data documented in medical records or when at least two interpretation. TD, JP contributed to the statistical analysis. TD contributed to readings of blood pressure were X140 mm Hg (systolic) or the draft preparation. Received 26 October 2006; revised 30 November 2006; accepted 30 X90 mm Hg (diastolic) after the acute phase of stroke. November 2006; published online 24 January 2007 Ischemic heart disease was diagnosed when there was a Hypoalbuminemia in acute ischemic stroke patients T Dziedzic et al 1319 history of angina pectoris or myocardial infarction. Diabetes cal deficit on admission measured in SSS than normoalbu- mellitus was diagnosed if its presence was documented in minemic subjects. medical records or patient was taking insulin or an oral Serum albumin level correlates significantly with age hypoglycemic agents or patients fulfilled the WHO criteria (r ¼À0.13, Po0.01), SSS score (r ¼ 0.14, Po0.01) (Figure 1), for diabetes 2 weeks after stroke onset (Alberti and Zimmet, body temperature on admission (r ¼À0.14, Po0.01), leuko- 1998). A patient was defined as a smoker if there was a cyte count (r ¼À0.17, Po0.01), fasting glucose (r ¼À0.16, history of cigarette smoking during the last 5 years. Po0.01), total cholesterol (r ¼ 0.14, Po0.01), LDL-cholesterol All patients underwent head computed tomography (CT) (r ¼ 0.12, Po0.01), HDL-cholesterol (r ¼ 0.09, Po0.01), scan within 24 h after stroke onset. a1-globulin (r ¼À0.48, Po0.01), a2-globulin (r ¼À0.49, Stroke severity on admission was assessed using Scandina- Po0.01), b-globulin (r ¼À0.26, Po0.01) and g-globulin vian Stroke Scale (SSS) (Scandinavian Stroke Study Group, (r ¼À0.35, Po0.01). 1985). Severe stroke was defined as SSS score p25. On univariate analysis, age was associated with increased Total serum protein, fasting glucose and cholesterol were risk of hypoalbuminemia (odds ratio (OR): 1.02, 95% measured within 36 h after stroke onset. Total serum protein confidence interval (CI): 1.00–1.03) and smoking was level was determined using Hitachi analyzer, and serum associated with decreased risk of hypoalbuminemia (OR: protein fractions (albumin, a-, b-, g-globulin) were measured 0.64, 95% CI: 0.45–0.91). Smokers were, however, signifi- using electrophoresis (Beckman Instruments, Fullerton, cantly younger than non-smokers (62.1711.5 vs 72.3711.9, USA). Total cholesterol, high-density lipoprotein (HDL), Po0.01). After adjusting for age, smoking was no longer cholesterol and triglycerides were determined by enzymatic significantly associated with risk of hypoalbuminemia method (Boeringher Mannheim) using analyzer RA-1000. (OR: 0.73, 95% CI: 0.50–1.06). Male gender (OR: 1.19, 95% Low-density lipoprotein (LDL) cholesterol was calculated CI: 0.88–1.62), hypertension (OR: 1.16, 95% CI: 0.85–1.60), by the Friedewald formula. Fasting glucose was measured diabetes mellitus (OR: 1.25, 95% CI: 0.87–1.80), ischemic by automated chemistry analyzer (Hitachi 917, Basel, heart disease (OR: 1.02, 95% CI: 0.75–1.37), myocardial Switzerland). infarction (OR: 1.11, 95% CI: 0.71–1.75) and atrial fibrilla- The study protocol was approved by the local Bioethics tion (OR: 0.95, 95% CI: 0.66–1.37) were not associated with Committee and informed consent was obtained from all risk of hypoalbuminemia. patients. To determine if hypoalbuminemia independently predicts The w2-test was used to compare proportions and Mann– stroke severity we created logistic regression model with Whitney’s test to compare continuous variables between dichotomised SSS score (p25) as dependent variable and groups. Spearman rank correlation test was used for correla- with hypoalbuminemia (serum albumin o35 g/l), age (con- tion analysis. Values of less than 0.05 were considerate to tinuous variable), atrial fibrillation and triglyceride (conti- indicate statistical significance. To determine the relation- nuous variable) as independent variables. Triglyceride and ship between hypoalbuminemia and stroke severity we used atrial fibrillation were put into the model, because we logistic regression analysis. previously demonstrated that these factors could influence stroke severity (Dziedzic et al., 2004a). Triglyceride level does not change significantly during stroke (Yan et al., 2005). Results Therefore, triglyceride concentration measured in acute stroke are likely to reflect pre-stroke value. Hypoalbumine- Seven hundred and five patients (age range 19–99 years) with mia (OR: 1.73, 95% CI: 1.23–2.43), age (OR: 1.03, 95% CI: first-ever ischemic stroke admitted to our stroke unit within 1.02–1.05) and triglyceride (OR: 0.68, 95% CI: 0.53–0.88), 24 h after stroke onset were included. They were recruited but not atrial fibrillation (OR: 1.41, 95% CI: 0.95–2.09) were from 979 patients with ischemic stroke hospitalized in our independently associated with severe stroke. stroke unit in the study period. Hypoalbuminemia defined as serum albumin level o35 g/l was found in 321 from 705 patients (45.5%). One hundred Discussion and sixty-seven patients had serum albumin level o30 g/l (23.7%). We found high frequency of hypoalbuminemia in unselected The characteristics of patients with hypoalbuminemia and cohort of acute stroke patients. Previous studies reported those with normoalbuminemia are shown in Table 1. significantly lower frequency of hypoalbuminemia in stroke The patients with hypoalbuminemia were older and less patients. Davalos et al. (1996) assessed malnutrition in 104 frequently smoker when compared with patients with patients with acute ischemic and hemorrhagic stroke. Serum normoalbuminemia. The patients with hypoalbuminemia albumin level was measured within 24 h after stroke onset, had significantly higher fasting glucose, leukocyte count, a-, and hypoalbuminemia (serum albumin level o35 g/l) was b-, g-globulin level and body temperature on admission observed in 7.7% of patients. Gariballa et al. (1998) found and lower total cholesterol and LDL-cholesterol level. The serum albumin concentration o35 g/l in 19% from 201 patients with hypoalbuminemia had more severe neurologi- ischemic stroke patients. In that study, serum albumin level

European Journal of Clinical Nutrition Hypoalbuminemia in acute ischemic stroke patients T Dziedzic et al 1320 Table 1 The characteristics of stroke patients with hypoalbuminemia and those with normoalbuminemia

Patients with serum albumin Patients with serum albumin P o35 g/l (n ¼ 321) X35 g/l (n ¼ 384)

Mean age (s.d.) (years) 71.1712.0 68.6712.9 0.01 Male, n (%) 138 (43.0) 182 (47.4) 0.24 Hypertension, n (%) 209 (65.1) 263 (68.5) 0.34 Diabetes mellitus, n (%) 74 (23.0) 74 (19.3) 0.22 Ischemic heart disease, n (%) 190 (59.2) 229 (59.6) 0.90 History of myocardial infarction, n (%) 38 (11.8) 50 (13.0) 0.64 Atrial fibrillation, n (%) 72 (22.4) 83 (21.6) 0.79 TIA prior to stroke, n (%) 27 (8.4) 33 (8.6) 0.93 Smoking, n (%) 68 (21.2) 113 (29.4) 0.01 Heart failure, n (%) 85 (26.5) 49 (12.8) o0.01 Renal insufficiency, n (%) 39 (12.1) 19 (4.9) o0.01 Fasting glucose (mmol/l), mean (s.d.) 6.7 (2.7) 5.9 (2.0) o0.01 TC (mmol/l), mean (s.d.) 5.3 (1.5) 5.5 (1.2) o0.01 LDL (mmol/l), mean (s.d.) 3.3 (1.2) 3.5 (1.1) 0.04 TG (mmol/l), mean (s.d.) 1.5 (0.9) 1.5 (0.9) 0.57 HDL (mmol/l), mean (s.d.) 1.4 (0.5) 1.4 (0.4) 0.18 Albumin (g/l), mean (s.d.) 28.8 (3.5) 40.4 (1.8) o0.01 a1-Globulin (g/l), mean (s.d.) 4.4 (1.8) 3.0 (1.5) o0.01 a2-Globulin, (g/l), mean (s.d.) 10.0 (3.0) 7.6 (1.8) o0.01 b-Globulin, (g/l), mean (s.d.) 10.8 (2.9) 9.4 (1.9) o0.01 g-Globulin, (g/l), mean (s.d.) 14.5 (5.2) 11.7 (3.1) o0.01 ESR (mm/h), mean (s.d.) 27.6 (26.1) 25.4 (22.4) 0.50 Leukocyte count (mmÀ3), mean (s.d.) 9491 (3575) 8379 (4175) o0.01 SBP on admission (mm Hg), mean (s.d.) 160 (28) 160 (30) 0.76 DBP on admission (mm Hg), mean (s.d.) 93 (15) 94 (16) 0.74 Body temperature on admission (1C), mean (s.d.) 36.8 (0.6) 36.7 (0.4) o0.01 SSS on admission, mean (s.d.) 28.5 (16.1) 34.2 (15.1) o0.01 Stroke subtype 0.04 TACI, n (%) 58 (18.1) 51 (13.3) 0.07 PACI, n (%) 169 (52.6) 210 (54.7) 0.59 LACI, n (%) 67 (20.9) 67 (17.4) 0.18 POCI, n (%) 25 (7.8) 54 (14.1) 0.01 unknown, n (%) 2 (0.6) 2 (0.5) —

Abbreviations: DBP, diastolic blood pressure; ESR, erythrocyte sedimentation rate; HDL, high-density lipoproteins cholesterol; LACI, lacunar infarction; LDL, low- density lipoproteins cholesterol; PACI, partial anterior circulation infarction; POCI, posterior circulation infarction; SBP, systolic blood pressure; SSS, Scandinavian Stroke Scale; TACI, total anterior circulation infarction; TC, total cholesterol; TG, triglycerides; TIA, transient ischemic attack.

were excluded from the study. Davis et al. (2004) measured serum albumin concentration in 185 patients with cerebral infarction and intracerebral hemorrhage within 24 h after stroke onset. They found hypoalbuminemia (serum albumin level p34 g/l) in 16.2% of patients. The frequency of hypoalbuminemia in our study is also higher than previously reported in patients admitted to Polish hospitals (20.7%) (Dzieniszewski et al., 2005). The difference in frequency of hypoalbuminemia between our study and previous reports could be to partially caused by patients selection (ischemic and hemorrhagic stroke vs only ischemic stroke; selected versus unselected cohort of patients), methods and timing of assessments; however, it does not explain several-fold higher frequency of hypoalbuminemia in Polish patients. Hypoalbuminemia in acute stroke patients could be a result of malnutrition and/or underlying disease processes Figure 1 Serum albumin vs SSS score in stroke patients. such as renal or hepatic insufficiency, uncontrolled heart failure, malignancy, etc. Protein energy malnutrition affects was measured within 48 h after stroke onset. In both the 8–30% of stroke patients on admission (Cairella et al., 2004), above-mentioned studies, patients with some concomitant and low serum albumin at admission is significantly disorders (e.g. liver disease, renal failure, malignancy, etc.) associated with premorbid nutrition (Davis et al., 2004).

European Journal of Clinical Nutrition Hypoalbuminemia in acute ischemic stroke patients T Dziedzic et al 1321 The high frequency of low serum albumin level among our could cause that serum albumin concentration might be stroke patients could be caused by malnutrition. Although influenced by acute-phase reaction. However, previous study our study was not design to investigate nutritional status of (Acalovschi et al., 2003) showed that acute-phase reaction stroke patients, the lower total cholesterol level in hypo- defined as CRP level is most pronounced until 3–7 days after albuminemic patients compared with normoalbuminemic stroke onset. subjects suggests malnutrition in the former. Additional studies are needed to determine the etiology of hypoalbuminemia in Polish stroke patients. Conclusion A few epidemiological studies suggest that low serum albumin level could be associated with increased risk of Results of our study suggest that hypoalbuminemia is a stroke. In one prospective study group with high serum frequent finding in Polish patients with acute stroke and it is albumin (444 g/l) vs low serum albumin (o42 g/l) had associated with more severe stroke and proinflammatory reduced stroke incidence (Gillum et al., 1994). In the cross- pattern of serum protein electrophoresis. sectional Norwegian Oslo Health Study, low albumin (p47 g/l) was associated with increased prevalence of self- reported stroke (OR: 1.83; 95% CI: 1.20–2.78) after adjusting Acknowledgements for age and sex (Hostmark and Tomten, 2006). It is proposed that chronic inflammation is common to The study was supported by grant from Jagiellonian the pathogenesis of malnutrition and vascular disease University. (Kaysen, 2006). Increased level of C-reactive protein (CRP) is independent risk factor for stroke (Rost et al., 2001; Cao et al., 2003). 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