title: Reduction in High-Sensitivity C-Reactive Protein Levels in Patients with Ischemic Stroke by Statin Treatment: Hs-CRP Sub-Study in J-STARS.
abstract: OBJECTIVE
  The pleiotropic effects of statins on recurrent stroke remain unclear. We investigated the effects of pravastatin on high-sensitivity C-reactive proteins (Hs-CRP) in ischemic stroke, and explored the impact of Hs-CRP on recurrent stroke and vascular events.
  
  
  METHODS
  This randomized open-label trial was ancillary to the J-STARS trial. One thousand and ninety-five patients with non-cardiogenic ischemic stroke were assigned to the pravastatin (n=545) or control groups (n=550). The primary and secondary endpoints were serum Hs-CRP reduction and stroke recurrence, including both ischemic and hemorrhagic ones, respectively. Onset of vascular events and each stroke subtype in relation to Hs-CRP levels were also determined.
  
  
  RESULTS
  In the pravastatin treatment group, Hs-CRP levels (median 711 µg/L, IQR 344-1500) significantly decreased 2 months later (median 592 µg/L, IQR 301-1390), and they remained significantly lower until the end of the study. However, in the control group, baseline Hs-CRP levels were similar to those 2 months later. The reduction of Hs-CRP levels from the baseline to 2 months in the pravastatin group was statistically significant compared with the control (p=0.007). One SD increase in log-transformed Hs-CRP increased the risk of stroke recurrence (HR 1.17, 95% CI 0.97-1.40) and vascular events (HR 1.30, 95% CI 1.12-1.51). With an Hs-CRP cut-off of 1000 µg/L, higher Hs-CRP significantly increased the risk of recurrent stroke (HR 1.50, 95% CI 1.03-2.17)and vascular events (HR 1.68, 95% CI 1.23-2.29).
  
  
  CONCLUSIONS
  In non-cardiogenic ischemic stroke, pravastatin treatment may reduce vascular inflammation as assessed by Hs-CRP, and higher Hs-CRP levels appeared to increase the risk of recurrent stroke and vascular events.
authors.affiliation: Department of Neurology, Tokyo Women's Medical University.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitagawa
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.affiliation: Center for Clinical Research, Kobe University Hospital.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Nagai
authors.affiliation: Foundation for Biomedical Research and Innovation, Translational Research Informatics Center.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kagimura
authors.affiliation: Stroke Center, Kindai University Hospital.
authors.forename: Toshiho
authors.initials: T
authors.lastname: Ohtsuki
authors.affiliation: Division of Biostatistics and Clinical Epidemiology, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences.
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.affiliation: National Cerebral and Cardiovascular Center.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Minematsu
authors.affiliation: Clinical Research Center, International University of Health and Welfare, Center for Brain and Cerebral Vessels, Sanno Hospital and Sanno Medical Center.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Uchiyama
authors.affiliation: National Cerebral and Cardiovascular Center.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Matsumoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D012008:Recurrence; D012306:Risk; D020521:Stroke / Q000097:blood* / Q000188:drug therapy*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002097:C-Reactive Protein; D017035:Pravastatin
keywords: C-reactive protein; Inflammation; Ischemic stroke; Statin