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Archived Comments for: Levels of acute phase proteins remain stable after ischemic stroke

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  1. C-reactive protein after acute ischaemic stroke, atherosclerosis and stroke subtypes

    Hedley Emsley, University of Liverpool

    9 March 2007

    We were interested to read the recent report by Elkind and colleagues [1] describing acute phase proteins after ischaemic stroke. This study provides further evidence that CRP concentrations measured using high-sensitivity assays are elevated in stroke patients. In our own study we favoured the use of age-, sex-, and atherosclerosis matched control subjects because all these factors can influence CRP concentrations and other inflammatory markers [2]. We have also previously commented, in relation to another study, that comparisons between stroke patients and healthy controls are likely to lead to overestimation of differences in inflammatory markers [3]. It is surprising that the study by Elkind et al. took no account of the degree of carotid atherosclerosis, particularly given their concluding remark, and comments in the abstract, that inflammatory biomarkers such as CRP are associated with atherosclerosis.

    Whilst we understand that only 21 patients were studied, it is worthy of comment that an unusually large proportion (33%) were classified as having lacunar strokes, whereas only 2 (10%) subjects were classified as having atherosclerotic strokes. The lacunar stroke subtype more typically constitutes 15% in hospital-based series. No data are presented on the acute phase proteins by stroke subtype, presumably in part because the small numbers would militate against any such subgroup analysis. However, whether such elevation in acute phase and inflammatory biomarkers occurs in patients with lacunar, or small vessel disease stroke is clearly of interest given the differences in pathophysiological mechanisms compared with large vessel atherosclerotic stroke. Recent data have been published both in favour of [4] and against [5] an association between elevated CRP and cerebral small vessel disease. Our own recent data suggest that inflammation and increased CRP are particularly associated with the extent of brain injury following stroke [6], so the high incidence of lacunar strokes, with less extensive acute brain injury, may explain why the increase in CRP during the first week in the study by Elkind et al. was not significant.

    Finally, the authors of the current report state that future studies should assess acute phase proteins at longer time intervals after stroke. In fact we reported on 36 acute stroke patients in whom we took serial blood samples up to 12 months [2]. We found median C-reactive protein (CRP) to be elevated, relative to controls (2.08 mg/l), from admission (4.31 mg/l) (p<0.001) until 3 months (2.90 mg/l) (p<0.01), the greatest elevation occurring at 5-7 days (17.67 mg/l) (p<0.001). By 12 months no significant difference were seen between surviving patients and control subjects: but this was of course controlled for atherosclerosis.

    1. Elkind MSV, Coates K, Tai W, Paik MC, Boden-Albala B, Sacco RL. Levels of acute phase proteins remain stable after ischemic stroke. BMC Neurol 2006;6:37

    2. Emsley HCA, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Hallenbeck JM, del Zoppo GJ, Rothwell NJ, Tyrrell PJ, Hopkins SJ. An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. J Neuroimmunol 2003;139:93-101

    3. Emsley HCA, Smith CJ, Georgiou RF, Vail A, Barberan EM, Rothwell NJ, Tyrrell PJ, Hopkins SJ. Interleukin-6 and acute ischaemic stroke. Acta Neurol Scand 2005;112:273-274

    4. van Dijk EJ, Prins ND, Vermeer SE, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM. C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation 2005;112:900-5

    5. Schmidt R, Schmidt H, Pichler M, Enzinger C, Petrovic K, Niederkorn K, Horner S, Ropele S, Watzinger N, Schumacher M, Berghold A, Kostner GM, Fazekas F. C-reactive protein, carotid atherosclerosis, and cerebral small-vessel disease: results of the Austrian Stroke Prevention Study. Stroke 2006;37:2910-6

    6. Smith CJ, Emsley HCA, Vail A, Georgiou RF, Rothwell NJ, Tyrrell PJ, Hopkins SJ. Variability of the systemic acute phase response after ischemic stroke. J Neurol Sci 2006;251:77-81.

    Hedley CA Emsley PhD MRCP

    Clinical Lecturer in Neurology

    Division of Neuroscience,

    The Walton Centre for Neurology & Neurosurgery,

    Lower Lane,

    Liverpool L9 7LJ


    Craig J Smith MD MRCP

    Stroke Association Clinical Fellow

    Division of Medicine and Neuroscience,

    The University of Manchester,

    Hope Hospital,



    Stephen J Hopkins PhD

    Principal Scientist and Honorary Senior Lecturer

    Injury Research,

    Hope Hospital,



    Competing interests