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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 70.0±8.9 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: >0.09µg/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. [ABSTRACT FROM AUTHOR]