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Randomized Controlled Trial
. 2017 Oct 1;24(10):1039-1047.
doi: 10.5551/jat.39354. Epub 2017 Mar 7.

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

Kazuo Kitagawa  1 , Naohisa Hosomi  2 , Yoji Nagai  3 , Tatsuo Kagimura  4 , Toshiho Ohtsuki  5 , Hideki Origasa  6 , Kazuo Minematsu  7 , Shinichiro Uchiyama  8 , Masakazu Nakamura  7 , Masayasu Matsumoto  2 ; J-STARS Investigators
Affiliations
Randomized Controlled Trial

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

Kazuo Kitagawa et al. J Atheroscler Thromb. .

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.

Keywords: C-reactive protein; Inflammation; Ischemic stroke; Statin.

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Conflict of interest statement

During the period of this study, Dr. Kitagawa reports receiving grants and lecture fees from Daiichi-Sankyo., Co., Ltd. Dr. Minematsu reports lecture fees from Daiichi Sankyo Co., Ltd. Dr. Uchiyama receives lecture fees from Daiichi Sankyo. Dr. Matsumoto reports grants and lecture fees from Daiichi Sankyo Co., LTD. Other authors had no conflicts of interest.

Figures

Fig. 1.
Fig. 1.
High-sensitivity C-reactive protein (Hs-CRP) level by treatment group. Open and closed circles represent mean with standard errors expressed by error bars. Statistical test was shown as the comparison from baseline within treatment group and between treatment groups in the MMRM model and multiplicity of the comparison was adjusted using Holm's method. *: p < 0.05 vs baseline, #: p < 0.05 vs control group.
Fig. 2.
Fig. 2.
Cumulative incidence of recurrent stroke and all vascular events according to high-sensitivity C-reactive protein (Hs-CRP) level during follow-up. (A) Stroke recurrence according to the tertiles of Hs-CRP. (B) All vascular events according to the tertiles of Hs-CRP. (C) Stroke recurrence according to the cut-off value (1000 µg/L) of Hs-CRP. (D) All vascular events according to the cut-off value (1000 µg/L) of Hs-CRP.
See this image and copyright information in PMC

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