Fevziye Burcu ŞİRİN, Kıvanç KARAMAN, Nesrin Gökben BECEREN, Önder TOMRUK, Özgür ÖNAL, Vedat Ali YÜREKLİ, Hamit Hakan ARMAĞAN, Derya YALÇIN YILMAZ, Abdurrahman ŞİMŞEK

ACİL SERVİSTE GEÇİCİ İSKEMİK ATAK TESPİTİNDE BİYOBELİRTEÇ OLARAK SERUM KOPEPTİN DÜZEYİ: PROSPEKTİF BİR VAKA KONTROL ÇALIŞMASI

Acil Servise (AS) başvuran TİA (Geçici iskemik atak) tanısı almış hastaların plazma kopeptin düzeylerini sağlıklı kontrollerle karşılaştırarak TİA saptamak için kopeptin’in tanısal doğruluğunu araştırmayı amaçladık.Acil servise nörolojik bir semptomla başvuran hastalar arasında ileriye dönük bir vaka kontrol çalışması yaptık. Nörolog tarafından TİA tanısı konan hastalar dahil edildi. 38 hastanın elektrokardiyografi, manyetik rezonans görüntüleme ve karotis doppler ultrasonografi tetkik sonuçları; Acil servis sonuçları (hastaneye yatış, taburculuk), risk grubu dağılımı (ABCD2 puanlarına göre) ve bir yıllık tekrar olay insidansına ilişkin değişkenler karşılaştırıldı. Ayrıca hastaların serum kopeptin düzeyleri sağlıklı kontrollerle karşılaştırıldı.Ortalama kopeptin düzeyi hasta grubunda 435.80 ± 316.45 pg/ml iken kontrol grubunda 770.20 ± 912.53 pg/ml idi. TİA'lı hastaların ortalama kopeptin düzeyi anlamlı olarak daha düşüktü (p = 0.018). TİA tanısında tüm katılımcılarda kopeptin 386.28 pg/ml cut-off değerinde %60.53 duyarlılık ve %68.42 özgüllüğe sahipti. Ayrıca 60 yaş üstü katılımcılarda kopeptin 460.37 pg/ml cut-off değerinde %75.86 duyarlılık ve %72.41 özgüllüğe sahipti.Bildiğimiz kadarıyla bu, bir serum biyobelirteçlerinin TİA tanısında yüksek etkinliğini gösteren ilk çalışmadır. Klinik şüphesi düşük ve kopeptin değeri düşük olan hastalarda acil hekimleri alternatif tanıları araştırmalıdır.

SERUM COPEPTIN LEVEL AS A BIOMARKER FOR DETECTING TRANSIENT ISCHEMIC ATTACK IN THE EMERGENCY ROOM: A PROSPECTIVE CASE-CONTROL STUDY

We aimed to investigate the diagnostic accuracy of copeptin to detect transient ischemic attack (TIA) by comparing the plasma copeptin levels of patients diagnosed with TIA who were admitted to the Emergency Department (ED) with those of healthy controls.We conducted a prospective case-control study among patients admitted to the ED with a neurological symptom. The patients diagnosed with TIA by the neurologist were included. The results of electrocardiography, magnetic resonance imaging, and carotid doppler ultrasonography investigations of 38 patients; the ED outcomes (hospitalization, discharge), the risk group distribution (according to ABCD2 scores), and the variables regarding one-year re-event incidence were compared. Additionally, the serum copeptin levels of the patients were compared to those of healthy controls.The mean copeptin level was 435.80 ± 316.45 pg/ml in the patient group, whereas it was 770.20 ± 912.53 pg/ml in the control group. The mean copeptin level ofpatients with TIA was significantly lower (p = 0.018). In the diagnosis of TIA, copeptin had 60.53% sensitivity and 68.42% specificity at a cut-off value of 386.28 pg/ ml, in all the participants. In addition, in participants above 60 years old, copeptin had 75.86% sensitivity and 72.41% specificity at a cut-off value of 460.37 pg/ml.To the best of our knowledge, this is the first study demonstrating the high efficacy of a serum biomarker in the diagnosis of TIA. Emergency physicians should search for alternative diagnoses in patients with a low degree of clinical suspicion and a lower copeptin value.

PDF

___

1. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke 2009; 40: 2276.
2. Johnston SC, Rothwell PM, Nguyen-Huynh MN, et al. Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack. Lancet 2007; 369: 283–92.
3. Merwick A, Albers GW, Amarenco P, et al. Addition of brain and carotid imaging to the ABCD2 score to identify patients at early risk of stroke after transient ischaemic attack: a multicentre observational study. Lancet Neurol 2010; 9: 1060–9.
4. Cucchiara BL, Messe SR, Sansing L, et al. Lipoprotein‐associated phospholipase A2 and C‐reactive protein for risk‐stratification of patients with TIA. Stroke 2009; 40: 2332–6.
5. Fassbender K, Schmidt R, Mössner R, et al. Pattern of activation of the hypothalamic-pituitary-adrenal axis in acute stroke. Relation to acute confusional state, extent of brain damage, and clinical outcome. Stroke 1994; 25: 1105–8. doi: 10.1161/01.STR.25.6.1105
6. Barreca T, Gandolfo C, Corsini G, et al. Evaluation of the secretory pattern of plasma arginine vasopressin in stroke patients. Cerebrovasc Dis 2001; 11: 113–8.
7. Baumann G, Dingman JF. Distribution, blood transport, and degradation of antidiuretic hormone in man. J Clin Invest. 1976; 57: 1109–16.
8. Robertson GL, Mahr EA, Athar S, et al. Development and clinical application of a new method for the radioimmunoassay of arginine vasopressin in human plasma. J Clin Invest. 1973; 52: 2340–52.
9. Christ-Crain M. Vasopressin and copeptin in health and disease. Rev Endocr Metab Disord 2019; 20: 283–94. doi.org/10.1007/s11154-019-09509-9.
10.Slowik A, Turaj W, Pankiewicz J, et al. Hypercortisolemia in acute stroke is related to the inflammatory response. J Neurol Sci. 2002 Apr 15;196(1-2):27-32. doi: 10.1016/s0022-510x(02)00018-7.
11.Ahmed N, de la Torre B, Wahlgren NG. Salivary cortisol, a biological marker of stress, is positively associated with 24-hour systolic blood pressure in patients with acute ischaemic stroke. Cerebrovasc Dis. 2004;18(3):206-13. doi: 10.1159/000079943.
12.Prabhakaran S, Silver AJ, Warrior L, et al. Misdiagnosis of transient ischemic attacks in the emergency room. Cerebrovasc. Dis. 2008; 26: 630–5.
13.Dolmans LS, Rutten F, Bartelink MEL, et al. Serum biomarkers in patients suspected of transient ischaemic attack in primary care: a diagnostic accuracy study. BMJ Open 2019; 9: e031774. doi: 10.1136/bmjopen-2019-031774
14.Restrepo L, Jacobs MA, Barker PB, et al. Assessment of transient ischemic attack with diffusion- and perfusion-weighted imaging. AJNR Am J Neuroradiol. 2004; 25: 1645–52.
15.Krol AL, Coutts SB, Simon JE, et al. Perfusion MRI abnormalities in speech or motor transient ischemic attack patients. Stroke. 2005; 36: 2487–2489.
16.Carroll BA. Duplex sonography in patients with hemispheric symptoms. J Ultrasound Med. 1989; 8:535–540.
17.Dobsa L, Edozien KC. Copeptin and its potential role in diagnosis and prognosis of various diseases. Biochem Med (Zagreb) 2013; 23(2): 172–90.
18.Xu Q, Tian Y, Peng H, et al. Copeptin as a biomarker for prediction of prognosis of acute ischemic stroke and transient ischemic attack: a meta-analysis. Hypertens Res 2017; 40: 465–71.
19.De Marchis GM, Weck A, Audebert H, et al. Copeptin for the prediction of recurrent cerebrovascular events after transient ischemic attack: results from the CoRisk study. Stroke 2014; 45: 2918–23.
20.Katan M, Nigro N, Fluri F, et al. Stress hormones predict cerebrovascular re-events after transient ischemic attacks. Neurology 2011; 76: 563–6.
21.Purroy F, Suárez-Luis I, Cambray S, et al. The determination of copeptin levels helps management decisions among transient ischaemic attack patients. Acta Neurol Scand 2015; 134: 140–7.
22.Bhattacharya P, Nagaraja N, Rajamani K, et al. Early use of MRI improves diagnostic accuracy in young adults with stroke. J Neurol Sci. 2013; 324(1-2): 62‐4. doi:10.1016/j.jns.2012.10.002