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

-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.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.-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).-VASc score did not significantly increase the predictive ability of the model

Receiver-operator characteristic analyses of the biomarkers and stroke risk scores predictive ability for unfavourable 30-day outcome of ischemic stroke and pairwise comparisons (Table 2).

<p>Receiver-operator characteristic analyses of the biomarkers and stroke risk scores predictive ability for unfavourable 30-day outcome of ischemic stroke and pairwise comparisons (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106439#pone-0106439-t002" target="_blank">Table 2</a>).</p

Crude associations of the CHA₂DS₂-VASc score and combinations of the score plus C-reactive protein, fibrinogen or TnI, or the CHA₂DS₂-VASc score plus all three biomarkers with unfavourable 30-day functional outcome of ischemic stroke and pairwise comparisons of the scores.

<p>CHA₂DS₂-VASc, congestive heart failure or left ventricular ejection fraction ≤40%, hypertension, age ≥75 years, diabetes mellitus, prior stroke or TIA, vascular disease (including myocardial infarction and peripheral artery disease), age >65 years, female gender (1 point each, age ≥75 years and prior stroke/TIA 2 points each); CHA₂DS₂-VASc-CRP, 1 additional point if C-reactive protein was >4 mg/L; CHA₂DS₂-VASc-F, 1 additional point if fibrinogen was >3.7 g/L; CHA₂DS₂-VASc-T, 1 additional point if TnI was >0.09µg/L; CHA₂DS₂-VASc-CRPFT, 1 additional point for each of three biomarkers if above the correspondent cut-off level.</p><p>Crude associations of the CHA₂DS₂-VASc score and combinations of the score plus C-reactive protein, fibrinogen or TnI, or the CHA₂DS₂-VASc score plus all three biomarkers with unfavourable 30-day functional outcome of ischemic stroke and pairwise comparisons of the scores.</p

Crude associations of biomarkers and the CHADS₂, CHA₂DS₂-VASc and HAS-BLED score with unfavourable 30-day outcome of ischemic stroke, predictive ability of each biomarker or score, and pairwise comparisons of each biomarker and stroke risk score predictive ability.

<p>OR, Odds Ratio; CI, Confidence Interval.</p><p>Only biomarkers with p<0.01 regarding unfavourable 30-day functional stroke outcome are shown.</p><p>CRP, C-reactive protein; WBC, white blood cell count; CrCl, creatinine clearance; CHA₂DS₂-VASc, congestive heart failure or left ventricular ejection fraction ≤40%, hypertension, age ≥75 years, diabetes mellitus, prior stroke or TIA, vascular disease (including myocardial infarction and peripheral artery disease), age >65 years, female gender (1 point each, age ≥75 years and prior stroke/TIA 2 points each); CHADS₂, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or TIA (1 point each, prior stroke/TIA 2 points); HAS-BLED, hypertension, abnormal renal or liver function, prior stroke, labile INRs (International Normalized Ratio), elderly (>65 years), concomitant drugs or alcohol use.</p><p>Crude associations of biomarkers and the CHADS₂, CHA₂DS₂-VASc and HAS-BLED score with unfavourable 30-day outcome of ischemic stroke, predictive ability of each biomarker or score, and pairwise comparisons of each biomarker and stroke risk score predictive ability.</p

Baseline blood biomarkers levels in patients with acute ischemic stroke according to favourable (mRS<3) or unfavourable 30-day functional stroke outcome, including in-hospital death (mRS≥3).

<p>Values are presented as n (%) or mean ± standard deviation or median with interquartile range (IQR). C-reactive protein is given in mg/L, fibrinogen in g/L, TnI in μg/L and D-dimer in μg/mL.</p><p>mRS, modified Rankin Scale (patients who died were assigned a mRS of 6); WBC, white blood cell count; CrCl, creatinine clearance; HDL, high density lipoprotein; LDL, low density lipoprotein.</p><p>Baseline blood biomarkers levels in patients with acute ischemic stroke according to favourable (mRS<3) or unfavourable 30-day functional stroke outcome, including in-hospital death (mRS≥3).</p

C-reactive protein, fibrinogen, TnI and D-dimer sensitivity, specificity and associated criterion for unfavourable 30-day outcome of ischemic stroke.

<p>C-reactive protein, fibrinogen, TnI and D-dimer sensitivity, specificity and associated criterion for unfavourable 30-day outcome of ischemic stroke.</p

Pairwise comparison of Receiver-operator characteristic of fully adjusted TnI, ‘classic’ and composed scores for unfavourable 30-day functional outcome of ischemic stroke.

<p>Pairwise comparison of Receiver-operator characteristic of fully adjusted TnI, ‘classic’ and composed scores for unfavourable 30-day functional outcome of ischemic stroke.</p

The adjusted associations of biomarkers, ‘classic’ scores and ‘composed’ scores with unfavourable 30-day functional outcome of ischemic stroke, with model discriminatory ability and goodness of model fit, and pairwise comparison of each model.

<p>OR, Odds Ratio; CI, Confidence Interval; ROC, Receiver Operating Characteristic; IDI – integrated discrimination index.</p><p>Only biomarkers or scores with significant association with unfavourable 30-day functional stroke outcome following adjustment are shown.</p><p>Cardiac TnI and fibrinogen adjusted for other biomarkers (white blood cell count, haemoglobin, haematocrit, C-reactive protein, D-dimer, creatinine clearance, total cholesterol, high-density lipoprotein and low-density lipoprotein), age, gender, body mass index, smoking status, alcohol consumption, NYHA class, atrial fibrillation, history of hypertension, heart failure, diabetes mellitus, chronic kidney disease, prior stroke/TIA, left atrial volume, left ventricular ejection fraction, the presence of mitral annular calcification and symptomatic haemorrhagic transformation of ischemic stroke.</p><p>The CHA₂DS₂-VASc score adjusted for CHADS₂ and HAS-BLED score, all biomarkers, gender, body mass index, smoking status, alcohol consumption, NYHA class, atrial fibrillation, chronic kidney disease, left atrial volume, left ventricular ejection fraction, the presence of mitral annular calcification and symptomatic haemorrhagic transformation of ischemic stroke.</p><p>The CHA₂DS₂-VASc-T and CHA₂DS₂-VASc-CRPFT scores adjusted for all blood biomarkers, gender, body mass index, smoking status, alcohol consumption, NYHA class, atrial fibrillation, chronic kidney disease, left atrial volume, left ventricular ejection fraction, the presence of mitral annulus calcification and symptomatic haemorrhagic transformation of ischemic stroke.</p><p>The adjusted associations of biomarkers, ‘classic’ scores and ‘composed’ scores with unfavourable 30-day functional outcome of ischemic stroke, with model discriminatory ability and goodness of model fit, and pairwise comparison of each model.</p

Baseline characteristic of patients with acute ischemic stroke according to favourable (mRS<3) or unfavourable 30-day functional stroke outcome (mRS≥3), including in-hospital death.

<p>Values are presented as n (%) or mean ± standard deviation or median with interquartile range (IQR).</p><p>mRS, modified Rankin Scale (patients who died were assigned a mRS of 6); NYHA, New York Heart Association; TIA, transient ischemic attack; CHADS₂, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or TIA; CHA₂DS₂-VASc, congestive heart failure or left ventricular ejection fraction ≤40%, hypertension, age ≥75 years, diabetes mellitus, prior stroke or TIA, vascular disease (including myocardial infarction and peripheral artery disease), age >65 years, female gender; HAS-BLED, hypertension, abnormal renal or liver function, prior stroke, labile INRs (International Normalized Ratio), elderly (>65 years), concomitant drugs or alcohol use; MAC, mitral annulus calcification; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker.</p><p>Baseline characteristic of patients with acute ischemic stroke according to favourable (mRS<3) or unfavourable 30-day functional stroke outcome (mRS≥3), including in-hospital death.</p