The Association of CHA2DS2-VASc Score and Blood Biomarkers with Ischemic Stroke Outcomes: The Belgrade Stroke Study

et al. (2014) The Association of CHA2DS2-VASc Score and Blood Biomarkers with Ischemic Stroke Outcomes: The Belgrade Stroke Study. PLoS ONE 9(9): e106439. doi:10.1371/journal.pone.0106439 The Association of CHA2DS2-VASc Score and Blood Biomarkers with Ischemic Stroke Outcomes: The Belgrade Stroke Study Tatjana S. Potpara 0 Marija M. Polovina 0 Dijana Djikic 0 Jelena M. Marinkovic 0 Nikola Kocev 0 Gregory Y. H. Lip 0 Ingo Ahrens, University Hospital Medical Centre, Germany 0 1 Faculty of Medicine, University of Belgrade, Belgrade, Serbia, 2 Cardiology Clinic, Clinical Center of Serbia , Belgrade , Serbia , 3 University Clinical Centre Gracanica, Kosovo, Serbia, 4 Institute for Medical Statistic and Informatic, University of Belgrade, Belgrade, Serbia, 5 University of Birmingham Centre for Cardiovascular Sciences, City Hospital , Birmingham , United Kingdom Background: Many blood biomarkers have a positive association with stroke outcome, but adding blood biomarkers to the National Institutes of Health Stroke Scale (NIHSS) did not significantly improve its discriminatory ability. We investigated the association of the CHA2DS2-VASc score with unfavourable functional outcome (defined as a 30-day modified Rankin Scale [mRS] $3) in patients presenting with acute ischemic stroke (AIS), and examined whether the addition of blood biomarkers (troponin I [TnI], fibrinogen, C-reactive protein [CRP]) affects the model discriminatory ability. Methods: We conducted an observational single-centre study of consecutive patients with AIS. All patients were admitted to hospital within 24 hours from the neurological symptoms onset. Results: Of 240 patients (mean age 70.068.9 years), unfavourable 30-day outcome occurred in 92 (38.3%). Patients with mRS$3 were older and more likely to have atrial fibrillation or other comorbidities (all p,0.001). They had higher levels of CRP, fibrinogen, TnI and higher CHA2DS2-VASc and CHADS2 scores (all p,0.05). The adjusted CHA2DS2-VASc score had excellent predictive ability for poor stroke outcome (c-statistic 0.982;95%CI,0.964-1.000, p,0.001). Whilst CRP had the highest sensitivity (83.7%), cardiac TnI was the most specific (97.3%) for prediction of poor stroke outcome (cut-off: . 0.09mg/L). Compared with each of these biomarkers, CHA2DS2-VASc score had significantly better predictive ability for poor stroke outcome (c-statistic for CRP, Fibrinogen and TnI was 0.853;95%CI,0.802-0.895, 0.848;95%CI,0.796-0.891, and 0.792;95%CI,0.736-0.842, all p,0.001, respectively, versus 0.932;95%CI,0.892-0.960, p,0.001 for the CHA2DS2-VASc, all p for the comparisons,0.01). There was no significant difference in the predictive ability of the CHA2DS2-VASc score vs. combinations of the CHA2DS2-VASc and TnI or TnI, fibrinogen and CRP (z statistic 0.369, p = 0.7119; integrated discrimination index 0.00801 and 0.00172, respectively, both p.0.05). Conclusions: The CHA2DS2-VASc score alone reliably predicts 30-day unfavourable outcome of stroke. Adding blood biomarkers to the CHA2DS2-VASc score did not significantly increase the predictive ability of the model. - Data Availability: The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files. Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. Introduction The early prediction of death or disability following acute ischemic stroke (AIS) presently relies upon clinical variables such as age and stroke severity, as measured by the National Institutes of Health Stroke Scale (NIHSS) [1,2]. These predictions are often broadly similar to the experienced stroke physicians clinical judgement [3], and continuous efforts are being made to improve the predictive ability of validated prognostic clinical variables by adding various biomarkers (whether blood, urine or imagingbased) to the original models based on clinical risk factors. Many blood-based biomarkers have been extensively studied as potential predictors of poor stroke outcome. However, most of the associations were relatively weak and no single class of biomarkers had a stronger association than the others [4]. Nevertheless, the effect of cardiac biomarkers was consistent, and a number of studies found an increased mortality in stroke patients with elevated cardiac troponin I (TnI) [57] or troponin T (TnT) [8,9]. Indeed, adding high-sensitivity TnT to several clinical variables including age and stroke severity resulted in incremental discrimination and reclassification of patients in one study [10], whilst another study showed that positive association of many biomarkers (including TnT) became statistically insignificant after adjustment for age and baseline NIHSS, and adding the NTerminal pro-BNP or Interleukin-6 (the only statistically significant biomarkers after the adjustment) to age plus NIHSS made no significant difference to the model discriminatory ability [11]. A recent study showed that the CHADS2 and CHA2DS2-VASc scores, which were originally formulated for risk assessment of stroke in patients with atrial fibrillation (AF) [12], were good predictors of 5-year outcomes in non-AF patients with AIS [13]. The CHA2DS2-VASc score correlated well with stroke severity in AF patients [14], and was a multivariate predictor of 90-day stroke outcome, independently of baseline NIHSS values [15]. The aim of the present study was to investigate the association of the CHA2DS2-VASc score with poor short-term (30-day) functional outcome in patients with AIS, regardless of the heart rhythm, and to examine whether the addition of TnI affects the model discriminatory ability regarding the poor short-term outcome of AIS. We tested the hypothesis that the CHA2DS2VASc score is significantly associated with poor short-term stroke outcome and that adding TnI improves the model predictive ability. Materials and Methods Patient selection and study design An observational single-centre study of consecutive patients presenting with AIS who were admitted to hospital during 2010 was conducted in the University Clinical Centre Gracanica. All patients gave written informed consent, and the University Clinical Centre Gracanica review board approved the study. All patients were admitted to hospital within 24 hours from the neurological symptoms onset. The diagnosis of AIS was established using the clinical evaluation and computed tomography (CT) of the brain within the first 24 hours of the event onset in all patients, and during hospitalization as needed. Patients with unclear timing of symptoms onset and those with haemorrhagic stroke or transient ischemic attack (TIA) were excluded (TIA was defined as a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction) [16]. Patients with a history of prior myocardial in (...truncated)