Clinical neuroscience
1447
Plasma levels of copeptin predict 1-year mortality in patients with acute ischemic stroke Chao-Wei Wang, Jian-Ling Wang, Yi Zhang, Qing Li, Shuang-Xi Guo and Si-Bei Ji To evaluate the association between plasma levels of copeptin and 1-year mortality in a cohort of Chinese patients with acute ischemic stroke. We prospectively studied 275 patients with ischemic stroke who were admitted within 24 h after the onset of symptoms. Copeptin and NIH stroke scale (NIHSS) score were measured at the time of admission. The prognostic value of copeptin to predict mortality within 1 year was compared with the NIHSS score and other known outcome predictors. Nonsurvivors had significantly higher copeptin levels on admission compared with survivors (P < 0.0001). Multivariate logistic regression analysis showed that elevated plasma levels of copeptin were an independent stroke mortality predictor, with an adjusted odds ratio of 4.48 [95% confidence interval (CI), 2.18–9.06]. The area under the receiver operating characteristic curve of copeptin was 0.882 (95% CI, 0.847–0.921) for stroke mortality, which yielded a sensitivity of 90.7% and a specificity of 84.5%.
Introduction Stroke is the second leading cause of mortality in China and one of the leading causes of severe morbidity [1]. Currently, the annual cost of stroke care in China is ∼ 40 billion RMB, 10 times higher than the care of cardiovascular diseases [2]. As in other countries, ischemic stroke is the most common type of stroke in China. It is accountable for 43–79% of all strokes. An early risk assessment with an estimate of the severity of disease and prognosis is pivotal for optimized care and allocation of healthcare resources. Vasopressin, a noncardiac plasma marker of cardiovascular disease, is released from the neurohypophysis in response to changes in plasma osmolality and is involved in osmoregulation and cardiovascular homeostasis [3]. However, vasopressin as such is not a useful plasma marker because it rapidly degrades in the circulation. Instead, copeptin, the C-terminal portion of provasopressin, is a 39-amino acid glycopeptide that has been found to be a stable and sensitive surrogate marker for vasopressin (AVP) release [4] and also seems to be useful in cardiovascular disease [5]. Because of the positive association of copeptin with the severity of illness and outcome, copeptin has been proposed as a prognostic marker in acute illness. In fact, it has been shown that copeptin measurement is useful for prognostic assessment in patients with cardiovascular diseases [6]. 0959-4965 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copeptin improved the NIHSS score (area under the curve of the combined model, 0.94; 95% CI, 0.91–0.97; P = 0.011). Elevated plasma copeptin levels at admission were an independent predictor of long-term mortality after ischemic stroke in a Chinese sample, suggesting that these alterations might play a role in the pathophysiology of stroke. NeuroReport 25:1447–1452 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. NeuroReport 2014, 25:1447–1452 Keywords: acute ischemic stroke, Chinese, copeptin, mortality Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China Correspondence to Si-Bei Ji, MD, Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, No. 88, Jiankang Road, Weihui, Henan 453100, People’s Republic of China Tel: + 86 0373 4404351; fax: + 86 0373 4404351; e-mail: [email protected] Received 22 September 2014 accepted 9 October 2014
Katan et al. [7] found that copeptin was a novel, independent prognostic marker improving the currently used risk stratification of stroke patients, whereas Zhang et al. [8] reported that copeptin levels were a novel and complementary biomarker to predict functional outcome after acute ischemic stroke (AIS). The aim of this study was to evaluate the association between plasma levels of copeptin and 1-year mortality in a cohort of Chinese patients with AIS.
Patients and methods We carried out a prospective cohort study at the emergency department of the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. From December 2011 to August 2013, all patients with firstever AIS were included. All patients were admitted within 24 h of experiencing a new focal or global neurological event. AIS was defined according to the WHO criteria. We excluded patients with malignant tumor, intracerebral hemorrhage, a history of recent surgery or trauma during the preceding 2 months, febrile disorders, and systemic infections at study enrollment, and autoimmune diseases with or without immunosuppressive therapy. The controls (100) had a similar age and sex distribution to the AIS patients. The median age of the controls included in this study was 68 [interquartile range (IQR), DOI: 10.1097/WNR.0000000000000290
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1448
NeuroReport 2014, Vol 25 No 18
60–79] years and 49% were women. They had no known diseases and were not using any medication. The present study has been approved by the ethics committee of the First Affiliated Hospital of Xinxiang Medical University. All participants or their relatives were informed of the study protocol and their written informed consent was obtained. The following demographical and clinical data were obtained: sex, age, leukocyte count, thrombocyte count, and history of conventional vascular risk factors (hypertension, diabetes mellitus, atrial fibrillation, hyperlipoproteinemia, smoking habit, and alcohol abuse). All patients received treatment according to the current guidelines. The cause of stroke was determined according to the criteria of the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification [9], which distinguishes large-artery arteriosclerosis cardio embolism, small-artery occlusion, other causative factor, and undetermined causative factor. The severity of stroke was assessed at admission by the National Institutes of Health Stroke Scale (NIHSS) score [10]. A baseline brain computed tomography (CT) and/or MRI scan were performed in all patients at admission. MRI with diffusion-weighted imaging was available in some stroke patients. In those patients, diffusion-weighted imaging lesion volumes were determined by one experienced neurologist unaware of the clinical and laboratory results. The lesion size was calculated by the commonly used semiquantitative method [11]. Lesions were categorized into three sizes to represent typical stroke patterns: (a) small lesion with a volume of less than 10 ml, (b) medium lesion of 10–100 ml, and (c) large lesion with a volume of more than 100 ml [12]. Copeptin measurement
All blood samples were collected on the first day of admission in a fasting state. Blood was obtained from an indwelling venous catheter. Results of the routine blood analyses were recorded. Plasma was frozen at − 70°C. Measurement was performed in a single batch using a commercial sandwich immunoluminometric assay (B.R.A.H.M.S. LUMItest CT-proAVP; B.R.A.H.M.S. AG, Hennigsdorf/Berlin, Germany) as described in detail elsewhere [7]. In our study, the lower detection limit was 0.4 pmol/l and the interassay and intra-assay coefficients of variation were found to be 2.0–4.5 and 2.4–5.7%. The median copeptin level in 100 healthy individuals was 4.1 pmol/l and the 97.5th percentile was 15.8 pmol/l. The median in healthy individuals using this modification was similar to that published in other studies in a Chinese sample (4.3 pmol/l in the study by Dong et al. [13] and 3.9 pmol/l in the study by Zhang et al. [8]). End points and follow-up
Functional outcome was obtained at year 1 according to the modified Rankin Scale (mRS) [14] blinded to copeptin levels. The primary end point of this study was the
functional outcome of stroke patients after 1 year from baseline. The secondary end point in stroke patients was death from any cause within the 1-year follow-up. Outcome assessment at 1 year was performed by one trained medical staff blinded to copeptin levels by a structured follow-up telephone interview with the patient or, if not possible, with the relative. Statistical analysis
Continuous variables were presented as mean ± SD or median (with IQR), and categorical variables as numbers and percentages. Univariate data on demographic and clinical features were compared using the Mann–Whitney U-test or the χ2-test as appropriate. Correlations among continuous variables were assessed by the Spearman rank-correlation coefficient. The influence of copeptin levels on mortality was assessed by logistic regression analysis, after adjusting for other variables, namely, age, sex, vascular risk factors, NIHSS score, stroke types and serum levels of D-dimer, fibrinogen, blood urea nitrogen, creatinine, glucose, and high-sensitivity-C-reactive protein (Hs-CRP). Results were expressed as adjusted odds ratios (ORs) with the corresponding 95% confidence interval (CI). Common logarithmic transformation (i.e. base 10) was performed to obtain a normal distribution for skewed variables (i.e. copeptin concentrations). Receiver operating characteristic curves were utilized to evaluate the accuracy of copeptin to predict death. The Kaplan–Meier cumulative survival curves were compared on the basis of copeptin quartiles. Data were analyzed statistically using STATA 9.2 (Stata Corp., College Station, Texas, USA). All probabilities were two tailed and P value less than 0.05 was considered significant.
Results Patient characteristics
Of consecutive admissions of 401 screened patients, 285 patients with AIS were included (48 with transient ischemic attack, 29 with onset of symptoms > 24 h, 13 without informed consent, six with epileptic seizures, 12 with systemic infections, and eight with a malignant tumor were excluded) and 275 completed follow-up (six lost to follow-up and four withdrew). The median age of patients with ischemic stroke included in this study was 68 (IQR, 60–79) years and 49.1% were women. A total of 198 out of the 275 patients lived in urban areas. In 199 patients, MRI was used to identify stroke, whereas in 128 patients, CT was used to identify stroke. Seventy-five patients died at the 1-year follow-up, and the mortality rate was thus 27.3%. Two-hundred patients were alive, with a median mRS score of 2 (IQR, 1–3). The baseline characteristics of the 275 patients presenting with AIS are described in Table 1. The results indicated that the plasma copeptin levels were significantly (P < 0.0001) higher in AIS patients compared with normal controls (16.1; IQR, 12.2–24.3 pmol/l and 4.1; IQR, 2.8–6.2 pmol/l, respectively). There was a significant correlation between the levels of plasma copeptin and the
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Copeptin predict mortality in stroke Wang et al. 1449
Table 1
Baseline characteristics of patients with stroke
Demographic characteristics N Female sex (%) Age (years) [median (IQR)] Stroke severity [median NIHSS score (IQR)] Admission to hospital (h) [median (IQR)] DWI lesion size (ml) (n) < 10 10–100 > 100 Hospital stay (days) [median (IQR)] TPA-T (n) Vascular risk factors (%) Hypertension Atrial fibrillation Hypercholesterolemia Diabetes mellitus Coronary heart disease Family history for stroke Active smokers Clinical findings [median (IQR)] Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Laboratory findings (IQR) Copeptin (pmol/l) Glucose (mmol/l) Hs-CRP (mg/dl) D-dimer (mg/l) White blood count (×109/l) Blood urea nitrogen (mg/dl) Creatinine (mg/dl) Stroke etiology (%) Small-vessel occlusive Large-vessel occlusive Cardioembolic Other Unknown
AIS
Nonsurvivors
Survivors
Pa
275 49.1 68 (60–79) 10 (6–15) 5.9 (2.7–10.4) 199 135 44 20 40 (20–63) 92
75 46.7 79 (68–88) 19 (12–42) 6.0 (2.8–11.0) 54 14 25 15 30 (14–57) 18
200 50.0 58 (50–66) 5 (2–10) 5.5 (2.5–10.1) 145 121 19 5 45 (25–69) 74
– NS 0.001 < 0.0001 NS
68.7 20.0 30.9 38.2 33.5 16.4 36.4
69.3 21.3 29.3 41.3 33.3 17.3 40.0
68.5 19.5 31.5 37.0 33.5 16.0 35.0
NS NS NS NS NS NS NS
155 (146–168) 85 (80–90)
165 (154–180) 95 (85–100)
148 (135–160) 80 (75–84)
0.006 0.009
16.1 (12.2–24.3) 6.65 (5.44–8.01) 0.98 (0.55–2.44) 2.4 (1.5–3.6) 9.0 (7.2–9.5) 26.5 (16.9–40.8) 1.27 (0.96–1.89)
32.1 (23.2–43.4) 7.03 (6.03–9.12) 1.65 (0.87–3.99) 3.5 (1.9–4.5) 9.4 (7.6–11.0) 31.4 (17.8–53.8) 1.42 (0.98–2.11)
14.3 (11.0–17.2) 6.22 (5.19–6.95) 0.44 (0.28–1.75) 2.0 (1.2–3.1) 8.6 (6.8–8.8) 23.3 (16.2–34.9) 1.23 (0.91–1.64)
< 0.0001 < 0.001 < 0.0001 0.006 0.432 0.008 0.033 NS
20.0 21.8 36.4 11.6 10.2
21.3 22.7 34.7 12.0 9.30
19.5 21.5 37.0 11.5 10.5
< 0.001 < 0.001 < 0.001 0.021 < 0.001
AIS, acute ischemic stroke; DWI, diffusion-weighted imaging; Hs-CRP, high-sensitivity-C-reactive protein; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale; NS, nonsignificant; TPA-T, tissue plasminogen activator-treated. a P value was assessed using the Mann–Whitney U-test or the χ2-test.
At 1 year, 75 patients (27.3%) had died. Nonsurvivors had significantly higher copeptin levels than survivors [32.1 (IQR, 23.2–43.4) vs. 14.3 (IQR, 11.0–17.2) pmol/l; P < 0.0001; Fig. 2]. In logistic regression analysis, we calculated the OR of log-transformed copeptin levels compared with the NIHSS score and other risk factors as presented in Table 2. After adjusting for all other significant predictors, copeptin remained an independent predictor of mortality, with an adjusted OR of 4.48 (95% CI, 2.18–9.06). In the subgroup of patients (n = 199) in whom MRI evaluations were performed, copeptin was an
Fig. 1
r[Spearman]=0.502, P
1447
Plasma levels of copeptin predict 1-year mortality in patients with acute ischemic stroke Chao-Wei Wang, Jian-Ling Wang, Yi Zhang, Qing Li, Shuang-Xi Guo and Si-Bei Ji To evaluate the association between plasma levels of copeptin and 1-year mortality in a cohort of Chinese patients with acute ischemic stroke. We prospectively studied 275 patients with ischemic stroke who were admitted within 24 h after the onset of symptoms. Copeptin and NIH stroke scale (NIHSS) score were measured at the time of admission. The prognostic value of copeptin to predict mortality within 1 year was compared with the NIHSS score and other known outcome predictors. Nonsurvivors had significantly higher copeptin levels on admission compared with survivors (P < 0.0001). Multivariate logistic regression analysis showed that elevated plasma levels of copeptin were an independent stroke mortality predictor, with an adjusted odds ratio of 4.48 [95% confidence interval (CI), 2.18–9.06]. The area under the receiver operating characteristic curve of copeptin was 0.882 (95% CI, 0.847–0.921) for stroke mortality, which yielded a sensitivity of 90.7% and a specificity of 84.5%.
Introduction Stroke is the second leading cause of mortality in China and one of the leading causes of severe morbidity [1]. Currently, the annual cost of stroke care in China is ∼ 40 billion RMB, 10 times higher than the care of cardiovascular diseases [2]. As in other countries, ischemic stroke is the most common type of stroke in China. It is accountable for 43–79% of all strokes. An early risk assessment with an estimate of the severity of disease and prognosis is pivotal for optimized care and allocation of healthcare resources. Vasopressin, a noncardiac plasma marker of cardiovascular disease, is released from the neurohypophysis in response to changes in plasma osmolality and is involved in osmoregulation and cardiovascular homeostasis [3]. However, vasopressin as such is not a useful plasma marker because it rapidly degrades in the circulation. Instead, copeptin, the C-terminal portion of provasopressin, is a 39-amino acid glycopeptide that has been found to be a stable and sensitive surrogate marker for vasopressin (AVP) release [4] and also seems to be useful in cardiovascular disease [5]. Because of the positive association of copeptin with the severity of illness and outcome, copeptin has been proposed as a prognostic marker in acute illness. In fact, it has been shown that copeptin measurement is useful for prognostic assessment in patients with cardiovascular diseases [6]. 0959-4965 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
Copeptin improved the NIHSS score (area under the curve of the combined model, 0.94; 95% CI, 0.91–0.97; P = 0.011). Elevated plasma copeptin levels at admission were an independent predictor of long-term mortality after ischemic stroke in a Chinese sample, suggesting that these alterations might play a role in the pathophysiology of stroke. NeuroReport 25:1447–1452 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. NeuroReport 2014, 25:1447–1452 Keywords: acute ischemic stroke, Chinese, copeptin, mortality Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China Correspondence to Si-Bei Ji, MD, Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, No. 88, Jiankang Road, Weihui, Henan 453100, People’s Republic of China Tel: + 86 0373 4404351; fax: + 86 0373 4404351; e-mail: [email protected] Received 22 September 2014 accepted 9 October 2014
Katan et al. [7] found that copeptin was a novel, independent prognostic marker improving the currently used risk stratification of stroke patients, whereas Zhang et al. [8] reported that copeptin levels were a novel and complementary biomarker to predict functional outcome after acute ischemic stroke (AIS). The aim of this study was to evaluate the association between plasma levels of copeptin and 1-year mortality in a cohort of Chinese patients with AIS.
Patients and methods We carried out a prospective cohort study at the emergency department of the First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. From December 2011 to August 2013, all patients with firstever AIS were included. All patients were admitted within 24 h of experiencing a new focal or global neurological event. AIS was defined according to the WHO criteria. We excluded patients with malignant tumor, intracerebral hemorrhage, a history of recent surgery or trauma during the preceding 2 months, febrile disorders, and systemic infections at study enrollment, and autoimmune diseases with or without immunosuppressive therapy. The controls (100) had a similar age and sex distribution to the AIS patients. The median age of the controls included in this study was 68 [interquartile range (IQR), DOI: 10.1097/WNR.0000000000000290
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1448
NeuroReport 2014, Vol 25 No 18
60–79] years and 49% were women. They had no known diseases and were not using any medication. The present study has been approved by the ethics committee of the First Affiliated Hospital of Xinxiang Medical University. All participants or their relatives were informed of the study protocol and their written informed consent was obtained. The following demographical and clinical data were obtained: sex, age, leukocyte count, thrombocyte count, and history of conventional vascular risk factors (hypertension, diabetes mellitus, atrial fibrillation, hyperlipoproteinemia, smoking habit, and alcohol abuse). All patients received treatment according to the current guidelines. The cause of stroke was determined according to the criteria of the TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification [9], which distinguishes large-artery arteriosclerosis cardio embolism, small-artery occlusion, other causative factor, and undetermined causative factor. The severity of stroke was assessed at admission by the National Institutes of Health Stroke Scale (NIHSS) score [10]. A baseline brain computed tomography (CT) and/or MRI scan were performed in all patients at admission. MRI with diffusion-weighted imaging was available in some stroke patients. In those patients, diffusion-weighted imaging lesion volumes were determined by one experienced neurologist unaware of the clinical and laboratory results. The lesion size was calculated by the commonly used semiquantitative method [11]. Lesions were categorized into three sizes to represent typical stroke patterns: (a) small lesion with a volume of less than 10 ml, (b) medium lesion of 10–100 ml, and (c) large lesion with a volume of more than 100 ml [12]. Copeptin measurement
All blood samples were collected on the first day of admission in a fasting state. Blood was obtained from an indwelling venous catheter. Results of the routine blood analyses were recorded. Plasma was frozen at − 70°C. Measurement was performed in a single batch using a commercial sandwich immunoluminometric assay (B.R.A.H.M.S. LUMItest CT-proAVP; B.R.A.H.M.S. AG, Hennigsdorf/Berlin, Germany) as described in detail elsewhere [7]. In our study, the lower detection limit was 0.4 pmol/l and the interassay and intra-assay coefficients of variation were found to be 2.0–4.5 and 2.4–5.7%. The median copeptin level in 100 healthy individuals was 4.1 pmol/l and the 97.5th percentile was 15.8 pmol/l. The median in healthy individuals using this modification was similar to that published in other studies in a Chinese sample (4.3 pmol/l in the study by Dong et al. [13] and 3.9 pmol/l in the study by Zhang et al. [8]). End points and follow-up
Functional outcome was obtained at year 1 according to the modified Rankin Scale (mRS) [14] blinded to copeptin levels. The primary end point of this study was the
functional outcome of stroke patients after 1 year from baseline. The secondary end point in stroke patients was death from any cause within the 1-year follow-up. Outcome assessment at 1 year was performed by one trained medical staff blinded to copeptin levels by a structured follow-up telephone interview with the patient or, if not possible, with the relative. Statistical analysis
Continuous variables were presented as mean ± SD or median (with IQR), and categorical variables as numbers and percentages. Univariate data on demographic and clinical features were compared using the Mann–Whitney U-test or the χ2-test as appropriate. Correlations among continuous variables were assessed by the Spearman rank-correlation coefficient. The influence of copeptin levels on mortality was assessed by logistic regression analysis, after adjusting for other variables, namely, age, sex, vascular risk factors, NIHSS score, stroke types and serum levels of D-dimer, fibrinogen, blood urea nitrogen, creatinine, glucose, and high-sensitivity-C-reactive protein (Hs-CRP). Results were expressed as adjusted odds ratios (ORs) with the corresponding 95% confidence interval (CI). Common logarithmic transformation (i.e. base 10) was performed to obtain a normal distribution for skewed variables (i.e. copeptin concentrations). Receiver operating characteristic curves were utilized to evaluate the accuracy of copeptin to predict death. The Kaplan–Meier cumulative survival curves were compared on the basis of copeptin quartiles. Data were analyzed statistically using STATA 9.2 (Stata Corp., College Station, Texas, USA). All probabilities were two tailed and P value less than 0.05 was considered significant.
Results Patient characteristics
Of consecutive admissions of 401 screened patients, 285 patients with AIS were included (48 with transient ischemic attack, 29 with onset of symptoms > 24 h, 13 without informed consent, six with epileptic seizures, 12 with systemic infections, and eight with a malignant tumor were excluded) and 275 completed follow-up (six lost to follow-up and four withdrew). The median age of patients with ischemic stroke included in this study was 68 (IQR, 60–79) years and 49.1% were women. A total of 198 out of the 275 patients lived in urban areas. In 199 patients, MRI was used to identify stroke, whereas in 128 patients, CT was used to identify stroke. Seventy-five patients died at the 1-year follow-up, and the mortality rate was thus 27.3%. Two-hundred patients were alive, with a median mRS score of 2 (IQR, 1–3). The baseline characteristics of the 275 patients presenting with AIS are described in Table 1. The results indicated that the plasma copeptin levels were significantly (P < 0.0001) higher in AIS patients compared with normal controls (16.1; IQR, 12.2–24.3 pmol/l and 4.1; IQR, 2.8–6.2 pmol/l, respectively). There was a significant correlation between the levels of plasma copeptin and the
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Copeptin predict mortality in stroke Wang et al. 1449
Table 1
Baseline characteristics of patients with stroke
Demographic characteristics N Female sex (%) Age (years) [median (IQR)] Stroke severity [median NIHSS score (IQR)] Admission to hospital (h) [median (IQR)] DWI lesion size (ml) (n) < 10 10–100 > 100 Hospital stay (days) [median (IQR)] TPA-T (n) Vascular risk factors (%) Hypertension Atrial fibrillation Hypercholesterolemia Diabetes mellitus Coronary heart disease Family history for stroke Active smokers Clinical findings [median (IQR)] Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Laboratory findings (IQR) Copeptin (pmol/l) Glucose (mmol/l) Hs-CRP (mg/dl) D-dimer (mg/l) White blood count (×109/l) Blood urea nitrogen (mg/dl) Creatinine (mg/dl) Stroke etiology (%) Small-vessel occlusive Large-vessel occlusive Cardioembolic Other Unknown
AIS
Nonsurvivors
Survivors
Pa
275 49.1 68 (60–79) 10 (6–15) 5.9 (2.7–10.4) 199 135 44 20 40 (20–63) 92
75 46.7 79 (68–88) 19 (12–42) 6.0 (2.8–11.0) 54 14 25 15 30 (14–57) 18
200 50.0 58 (50–66) 5 (2–10) 5.5 (2.5–10.1) 145 121 19 5 45 (25–69) 74
– NS 0.001 < 0.0001 NS
68.7 20.0 30.9 38.2 33.5 16.4 36.4
69.3 21.3 29.3 41.3 33.3 17.3 40.0
68.5 19.5 31.5 37.0 33.5 16.0 35.0
NS NS NS NS NS NS NS
155 (146–168) 85 (80–90)
165 (154–180) 95 (85–100)
148 (135–160) 80 (75–84)
0.006 0.009
16.1 (12.2–24.3) 6.65 (5.44–8.01) 0.98 (0.55–2.44) 2.4 (1.5–3.6) 9.0 (7.2–9.5) 26.5 (16.9–40.8) 1.27 (0.96–1.89)
32.1 (23.2–43.4) 7.03 (6.03–9.12) 1.65 (0.87–3.99) 3.5 (1.9–4.5) 9.4 (7.6–11.0) 31.4 (17.8–53.8) 1.42 (0.98–2.11)
14.3 (11.0–17.2) 6.22 (5.19–6.95) 0.44 (0.28–1.75) 2.0 (1.2–3.1) 8.6 (6.8–8.8) 23.3 (16.2–34.9) 1.23 (0.91–1.64)
< 0.0001 < 0.001 < 0.0001 0.006 0.432 0.008 0.033 NS
20.0 21.8 36.4 11.6 10.2
21.3 22.7 34.7 12.0 9.30
19.5 21.5 37.0 11.5 10.5
< 0.001 < 0.001 < 0.001 0.021 < 0.001
AIS, acute ischemic stroke; DWI, diffusion-weighted imaging; Hs-CRP, high-sensitivity-C-reactive protein; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale; NS, nonsignificant; TPA-T, tissue plasminogen activator-treated. a P value was assessed using the Mann–Whitney U-test or the χ2-test.
At 1 year, 75 patients (27.3%) had died. Nonsurvivors had significantly higher copeptin levels than survivors [32.1 (IQR, 23.2–43.4) vs. 14.3 (IQR, 11.0–17.2) pmol/l; P < 0.0001; Fig. 2]. In logistic regression analysis, we calculated the OR of log-transformed copeptin levels compared with the NIHSS score and other risk factors as presented in Table 2. After adjusting for all other significant predictors, copeptin remained an independent predictor of mortality, with an adjusted OR of 4.48 (95% CI, 2.18–9.06). In the subgroup of patients (n = 199) in whom MRI evaluations were performed, copeptin was an
Fig. 1
r[Spearman]=0.502, P
