Systemic Inflammatory Response Depends on Initial Stroke Severity but Is Attenuated by Successful Thrombolysis
To the Editor:
We read with interest the article by Audebert et al1 concerning inflammatory response in patients with acute ischemic stroke. The authors describe an association between inflammatory parameters and stroke severity, as well as stroke volume measured by cranial computed tomography (CCT) and magnetic resonance imaging. Moreover, they analyzed in more detail the subgroup of patients receiving thrombolysis and found that the inflammatory markers were significantly lower in patients with improvement after recombinant tissue plasminogen activator treatment.
This is an additional important study concerning inflammation in acute stroke and supports other investigations analyzing C-reactive protein (CRP) in acute ischemic stroke.2–5 The largest study up to now was recently published by Di Napoli et al6 and could demonstrate that elevated levels of CRP were related to the risk of new cardiovascular events.
In general, the findings of the recent study corroborate our results concerning the prognostic relevance of early serial CRP measurements in 127 patients with acute ischemic stroke.5 In our study, the first CRP measurement was performed within 12 hours after symptom onset (mean, 5.0 hours). The second CRP measurement was performed within 24 hours after symptom onset (mean, 19.6 hours). The third was performed 24 hours after the second measurement (mean, 43.1 hours). We also determined the lesion volume on diffusion-weighted imaging (DWI) in a subgroup of 43 patients in which the DWI was performed within 12 hours after symptom onset. However, we only observed a significant association between the third CRP value and the DWI lesion size. In contrast, Audebert et al1 described a significant association between inflammatory response and lesion size already for the first CRP measurement regarding all included patients. These differences might be explained by the use of different imaging techniques: DWI within 12 hours after symptom onset in our investigation and CCT or T2-weighted magnetic resonance imaging in the study by Audebert et al,1 as well as the later CRP determination (first CRP within 24 hours after symptom onset). Furthermore, one possible limitation of the study is the fact that follow-up imaging is not performed in every patient and that the lesion volume measured with early CCT might be underestimated. In our opinion, it would be helpful to know in which proportion of patients only a CCT was performed and how long the time interval between symptom onset, imaging, and the first CRP measurement was. In our opinion, the main novel finding of Audebert et al1 was the observation of significant lower CRP values during follow-up in patients who improve after thrombolysis.
Audebert HJ, Rott MM, Eck T, Haberl RL. Systemic inflammatory response depends on initial stroke severity but is attenuated by successful thrombolysis. Stroke. 2004; 35: 2128–2133.
Muir KW, Weir CJ, Alwan W, Squire IB, Lees KR. C-reactive protein and outcome after ischemic stroke. Stroke. 1999; 30: 981–985.
Di Napoli M, Papa F, Bocola V. Prognostic influence of increased c-reactive protein and fibrinogen levels in ischemic stroke. Stroke. 2001; 32: 133–138.
Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: An independent prognostic factor. Stroke. 2001; 32: 917–924.
Winbeck K, Poppert H, Etgen T, Conrad B, Sander D. Prognostic relevance of early serial c-reactive protein measurements after first ischemic stroke. Stroke. 2002; 33: 2459–2464.
Di Napoli M, Papa F. Inflammation, hemostatic markers, and antithrombotic agents in relation to long-term risk of new cardiovascular events in first-ever ischemic stroke patients. Stroke. 2002; 33: 1763–1771.
We thank Dr Sander for her very interesting comment. She reported a positive correlation of C-reactive protein (CRP) with infarct size in diffusion-weighted (DWI) magnetic resonance imaging in a substudy of 43 patients. This correlation was only seen in the third CRP measurement after >24 hours. This observation fits our findings, but in the analysis of Winbeck et al CRP levels before 12 hours and between 12 and 24 hours were not associated with larger lesion volume. This is in contrast to our results in which the first CRP measurement (mean, 6.8 hours after onset) already had a positive correlation (P<0.05).
A direct comparison of the analyses is difficult for different reasons. The image analysis in Winbeck et al was performed with early DWI scans within 12 hours of onset. It is known that DWI signals are partially reversible. However, volume measurements in computed tomography scans, as mainly used in our sample, can differ in the same patients because of the infarct edema.
The statistical methods were different. In the study of Winbeck et al, the CRP values were dichotomized into 2 groups (< or ≥0.86 mg/dL), whereas in our analysis the Spearman correlation coefficient was used for all values.
The sample of Winbeck et al was smaller, but the analysis was performed prospectively, whereas our study had a retrospective design. The most important message of our study was that in acute stroke, inflammation parameters increase independently of infectious complications, but this inflammatory response can be stopped by successful thrombolysis.