Letters

C reactive protein and acute phase of ischaemic stroke

EDITORHigher C reactive protein concentrations indicate increased risk of coronary and cerebrovascular events in otherwise healthy individuals¹ and a worse prognosis in myocardial infarction² and ischaemic stroke.³ According to Pepys and Berger, the available data support its potential role as a marker of cardiovascular risk.⁴ To be of clinical use, however, the protein must have an independent prognostic value over and above that of the data already routinely available.

In patients with acute myocardial infarction or ischaemic stroke the extent of necrosis is the main but not the only determinant of prognosis. Age and vascular comorbidity are not necessarily related to infarct size but are nevertheless important predictors of prognosis. The reasons for a variable response to the necrotic insult are probably multiple and require a clear understanding as they may represent independent additional determinants of prognosis.

I looked again at data that colleagues and I obtained in a cohort of patients after ischaemic stroke.³ The C reactive protein concentrations increased (5 mg/l) in about three quarters of patients within 24 hours after ischaemic stroke, and higher values were significantly associated with large infarct size (60% (n=87/146) v 26% (n=12/47); P<0.0001, ² test) and worse outcome (36% (n=52) v 9% (n=4); P=0.0008, log rank test). Smaller increases were reported in patients with small infarcts (median 8 mg/l (25th to 75th centile 3.8 to 26.3 mg/l) v 18 mg/l (10 to 35 mg/l); P=0.0002, Mann-Whitney U test) and deep infarcts (8 mg/l (3 to 26 mg/l) v 19 mg/l (10 to 46 mg/l); P<0.0001).

The strong association between infarct size and increased C reactive protein concentrations may result from accurate quantification of cerebral infarction by computed tomography and from a variable intensity of the acute phase response to inflammatory stimuli (in this case, the extent of cerebral infarction). This possibility is suggested by the observation that 24 hour concentrations were much higher in patients with previous raised concentrations.⁵

If the intensity of the acute phase response was not proportional to the intensity of the inflammatory stimulus, the variable increase in the C reactive protein concentration might not just be a consequence of late recanalisation or persistent occlusion of the infarct related artery. Thus the prognostic importance of the 24 hour concentration may be related partly to the extent of the necrosis and partly to the unknown individual determinants of the intensity of the acute phase response. C reactive protein might indicate the inflammatory status during the acute phase of ischaemic stroke and might aid in current challenges posed in secondary prevention.

Mario Di Napoli, consultant neurologist. 
Department of Neurology and Neurorehabilitation, Casa di Cura Villa Pini d'Abruzzo, 661080 Chieti, Italy mariodinapoli{at}katamail.com