Reduction in High-Sensitivity C-Reactive Protein Levels in Patients with Ischemic Stroke by Statin Treatment: Hs-CRP Sub-Study in J-STARS

Abstract

Aims: 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).Conclusion: 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.

Stabilization of symptomatic carotid atherosclerotic plaques by statins: a clinico-pathological analysis

“…Therefore, further histopathological analyses may reveal a significantly less prominent infiltration by foamy macrophages in patients previously treated with statins. Fourth, we did not measure other biomarkers such as high-sensitivity C-reactive protein, which is associated with the risk of ischemic stroke and vascular events [ 51 ].…”

Long-Term Effect of Pravastatin on Carotid Intima–Media Complex Thickness

“…The J-STARS trial also has other substudies, including those focusing on high-sensitivity C-reactive protein (ClinicalTrials.gov NCT00361699, University Hospital Medical Information Network C000000211), 31 development of dementia, and genetic aspects (University Hospital Medical Information Network C000008055). We will further investigate relationships of carotid IMT with the above topics of interest during statin treatment.…”

Pravastatin Reduces the Risk of Atherothrombotic Stroke when Administered within Six Months of an Initial Stroke Event

“…Secondary endpoints contained the onset of each stroke subtype, myocardial infarction, vascular accident, death, and hospitalization. The diagnostic criteria for each stroke subtype, TIA, myocardial infarction, and vascular accidents were shown in previous reports 6 , 8 , 10 ) . Particularly, stroke and other vascular events were adjudicated by the central event evaluation committees.…”