Comparison of acute versus convalescent stage high-sensitivity C-Reactive protein level in predicting clinical outcome after acute ischemic stroke and impact of erythropoietin

Abstract

Background and aim: Currently, no data on the optimal time point after acute ischemic stroke (IS) at which high-sensitivity C-reactive protein (hs-CRP) level is most predictive of unfavorable outcome. We tested the hypothesis that hs-CRP levels during both acute (48 h after IS) and convalescent (21 days after IS) phases are equally important in predicting 90-day clinical outcome after acute IS. We further evaluated the impact of erythropoietin (EPO), an anti-inflammatory agent, on level of hs-CRP after acute IS.

Methods: Totally 160 patients were prospectively randomized to receive either EPO therapy (group 1, n = 80) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or placebo (group 2, n = 80). Serum level of hs-CRP was determined using ELISA at 48 h and on day 21 after IS and once in 60 healthy volunteers.

Results: Serum level of hs-CRP was substantially higher in all patients with IS than in healthy controls at 48 h and day 21 after IS (all p < 0.001). Levels of hs-CRP did not differ between group 1 and 2 at 48 h and day 21 after IS (all p > 0.5). Multivariate analysis showed that hs-CRP levels (at 48 h and day 21) were independently predictive of 90-day major adverse neurological event (MANE) (defined as recurrent stroke, NIHSS≥8, or death) (all p < 0.03), whereas EPO therapy was independently predictive of reduced 90-day MANE (all p < 0.02).

Conclusion: EPO therapy which was independently predictive of freedom from 90-day MANE did not alter the crucial role of hs-CRP levels measured at 48 h and 21-day in predicting unfavorable clinical outcome after IS.

Figure 1

Receiver operating characteristics (ROC) curve analysis revealed that the serum level of CRP ≥ 2.985 mg/L at 48 h after acute IS was the most powerful predictor of 90-day MANE with a sensitivity of 76.8%, a specificity of 82.7%, p < 0.001.

Figure 2

Spearman's rank test for the correlation between serum level of high-sensitivity C-reactive protein (hs-CRP) and National Institutes Health Stroke Scale (NIHSS) at 48 h after acute ischemic stroke (p < 0.001; r = 0.467).

Figure 3

Spearman's rank test for the correlation between serum level of hs-CRP and modified Ranking Stroke Scale (RSS) at 48 h after acute ischemic stroke (p < 0.001; r = 0.430).

Figure 4

Spearman's rank test for the correlation between serum level of hs-CRP and Barthel index at 48 h after acute ischemic stroke (p < 0.001; r = -0.459).

Figure 5

Spearman's rank test for the correlation between 21 -day serum level of high-sensitivity C-reactive protein (hs-CRP) and National Institutes Health Stroke Scale (NIHSS) at 90-day after acute ischemic stroke (p = 0.003; r = 0.247).