Serum C-Reactive Protein Concentration and Genotype in Relation to Ischemic Stroke Subtype

Background and Purpose— C-reactive protein (CRP) has evolved as an inflammatory risk marker of cardiovascular disease. Several single-nucleotide polymorphisms at the CRP locus have been found to be associated with CRP levels. The aim of the present study was to investigate CRP levels and genetic variants in etiological subtypes of ischemic stroke. Methods— The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) comprises 600 consecutive ischemic stroke cases (18 to 69 years) and 600 matched controls from western Sweden. Stroke subtypes were defined by the TOAST classification. Serum CRP levels were determined by a high-sensitivity immunometric assay. Results— CRP levels were significantly higher for all ischemic stroke subtypes compared with controls, both in the acute phase and at the 3-month follow-up. After adjustment for traditional risk factors, CRP at follow-up was related to higher odds ratios (ORs) of overall ischemic stroke (OR, 1.25; 95% CI, 1.09 to 1.43) and large-vessel disease (OR, 1.48; 95% CI, 1.09 to 2.00). The CRP −286C>T>A, 1059G>C, and 1444C>T single-nucleotide polymorphisms showed significant associations with CRP levels. However, neither CRP genotypes nor haplotypes showed an association to overall ischemic stroke. Conclusions— This is the first large study on CRP in different TOAST subtypes in a young ischemic stroke population. CRP levels differed between etiological subtypes of ischemic stroke both in the acute phase and at the 3-month follow-up. CRP at follow-up was associated with overall ischemic stroke and the large-vessel disease subtype. Genetic variants at the CRP locus were associated with CRP levels, but no association was detected for overall ischemic stroke.

[1]  Á. Chamorro.  Role of Inflammation in Stroke and Atherothrombosis , 2004, Cerebrovascular Diseases.

[2]  À. Rovira,et al.  C-Reactive Protein Predicts Further Ischemic Events in First-Ever Transient Ischemic Attack or Stroke Patients With Intracranial Large-Artery Occlusive Disease , 2003, Stroke.

[3]  Natalia S. Rost,et al.  Plasma Concentration of C-Reactive Protein and Risk of Ischemic Stroke and Transient Ischemic Attack: The Framingham Study , 2001, Stroke.

[4]  S. Humphries,et al.  Human CRP Gene Polymorphism Influences CRP Levels: Implications for the Prediction and Pathogenesis of Coronary Heart Disease , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[5]  J. Volanakis,et al.  Human C-reactive protein: expression, structure, and function. , 2001, Molecular immunology.

[6]  C. Ladenvall,et al.  Family History in Ischemic Stroke Before 70 Years of Age: The Sahlgrenska Academy Study on Ischemic Stroke , 2005, Stroke.

[7]  M. Lathrop,et al.  Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein. , 2002, Cardiovascular research.

[8]  Marc Fisher,et al.  The Ischemic Penumbra: Identification, Evolution and Treatment Concepts , 2003, Cerebrovascular Diseases.

[9]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

[10]  P. Ridker,et al.  High-sensitivity C-reactive protein: clinical importance. , 2004, Current problems in cardiology.

[11]  K. Lees,et al.  C-reactive protein and outcome after ischemic stroke. , 1999, Stroke.

[12]  Farzaneh A. Sorond,et al.  Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis , 2005, The Lancet Neurology.

[13]  C. Enzinger,et al.  Markers of Endothelial and Hemostatic Activation and Progression of Cerebral White Matter Hyperintensities: Longitudinal Results of the Austrian Stroke Prevention Study , 2005, Stroke.

[14]  D. Sander,et al.  Evaluation of C-Reactive Protein Measurement for Assessing the Risk and Prognosis in Ischemic Stroke: A Statement for Health Care Professionals From the CRP Pooling Project Members , 2005, Stroke.

[15]  D. Tregouet,et al.  A new algorithm for haplotype‐based association analysis: the Stochastic‐EM algorithm , 2004, Annals of human genetics.

[16]  C. Carlson,et al.  Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. , 2005, American journal of human genetics.

[17]  M. D. de Maat,et al.  C-reactive protein as a risk factor versus risk marker , 2004, Current opinion in lipidology.

[18]  B. Coull,et al.  Interleukin‐6 and interleukin‐1 receptor antagonist in acute stroke , 1995, Annals of neurology.

[19]  L. Hansson,et al.  A novel common single nucleotide polymorphism in the promoter region of the C-reactive protein gene associated with the plasma concentration of C-reactive protein. , 2005, Atherosclerosis.

[20]  B. Norrving,et al.  Comparison of Clinical and Neuroradiological Findings in First‐Ever Stroke: A Population‐Based Study , 1994, Stroke.

[21]  A. Grau,et al.  Inflammation and Infections as Risk Factors for Ischemic Stroke , 2003, Stroke.

[22]  M. Di Napoli,et al.  Prognostic Influence of Increased C-Reactive Protein and Fibrinogen Levels in Ischemic Stroke , 2001, Stroke.

[23]  T. Spector,et al.  Genetic effects on baseline values of C-reactive protein and serum amyloid a protein: a comparison of monozygotic and dizygotic twins. , 2004, Clinical chemistry.

[24]  D. Allison,et al.  Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level , 2005, Journal of Molecular Medicine.

[25]  J. Pankow,et al.  Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. , 2001, Atherosclerosis.

[26]  N. Cook,et al.  Association of Common CRP Gene Variants with CRP Levels and Cardiovascular Events , 2005, Annals of human genetics.