Dataset Information

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

ABSTRACT: 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.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.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).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.

SUBMITTER: Kitagawa K

PROVIDER: S-EPMC5656766 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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

Kitagawa Kazuo K Hosomi Naohisa N Nagai Yoji Y Kagimura Tatsuo T Ohtsuki Toshiho T Origasa Hideki H Minematsu Kazuo K Uchiyama Shinichiro S Nakamura Masakazu M Matsumoto Masayasu M

Journal of atherosclerosis and thrombosis 20170307 10

<h4>Aims</h4>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.<h4>Methods</h4>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). Th ...[more]

PMID: 28302952

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Project description:BackgroundHigh sensitivity C-reactive protein (hsCRP) levels are shown to be influenced by genetic variants in Europeans; however, little is explored in Indian population.MethodsHerein, we comprehensively evaluated association of all previously reported genetic determinants of hsCRP levels, including 18 cis (proximal to CRP gene) and 73 trans-acting (distal to CRP gene) variants in 4,200 North Indians of Indo-European ethnicity. First, we evaluated association of 91 variants from 12 candidate loci with hsCRP levels in 2,115 North Indians (1,042 non-diabetic subjects and 1,073 patients with type 2 diabetes). Then, cis and trans-acting variants contributing maximally to hsCRP level variation were further replicated in an independent 2,085 North Indians (1,047 patients with type 2 diabetes and 1,038 non-diabetic subjects).ResultsWe found association of 12 variants from CRP, LEPR, IL1A, IL6, and IL6R with hsCRP levels in non-diabetic subjects. However, only rs3093059-CRP [β = 0.33, P = 9.6×10⁻⁵] and the haplotype harboring rs3093059 risk allele [β = 0.32 µg/mL, P = 1.4×10⁻⁴/P(perm) = 9.0×10⁻⁴] retained significance after correcting for multiple testing. The cis-acting variant rs3093059-CRP had maximum contribution to the variance in hsCRP levels (1.14%). Among, trans-acting variants, rs1892534-LEPR was observed to contribute maximally to hsCRP level variance (0.59%). Associations of rs3093059-CRP and rs1892534-LEPR were confirmed by replication and attained higher significance after meta-analysis [β(meta) = 0.26/0.22; P(meta) = 4.3×10⁻⁷/7.4×10⁻³ and β(meta) = -0.15/-0.12; P(meta) = 2.0×10⁻⁶/1.6×10⁻⁶ for rs3093059 and rs1892534, respectively in non-diabetic subjects and all subjects taken together].ConclusionIn conclusion, we identified rs3093059 in CRP and rs1892534 in LEPR as major cis and trans-acting contributor respectively, to the variance in hsCRP levels in North Indian population.

Project description:Background The aim of this study was to investigate the association between hsCRP (high-sensitivity C-reactive protein) and prognosis over time after stroke onset. Methods and Results In this prespecified prospective substudy of the Third China National Stroke Registry, a total of 9438 patients with acute ischemic stroke or transient ischemic attack and measured hsCRP were included. Patients were categorized into 3 groups according to the sampling time after index onset (<24 hours, 24-72 hours, 72 hours-8 days). The outcomes consisted of stroke recurrence and combined vascular events within 1 year, and dependence or death defined as modified Rankin Scale score of 3 to 6 at 1 year. The associations between hsCRP and outcomes in different groups were analyzed by using Cox proportional hazards and logistic regression models. The median levels of hsCRP within 24 hours, between 24 and 72 hours and between 72 hours and 8 days were 2.01, 1.72, and 1.72 mg/L, respectively (P < 0.05). Compared with the bottom quartile, patients in the top quartile measured within 72 hours were at increased risk of recurrent stroke (<24 hours: adjusted hazard ratio [HR], 1.57 [95% CI, 1.05-2.35], P = 0.03; 24-72 hours: adjusted HR, 1.60 [95% CI, 1.18-2.17], P = 0.003). Association was attenuated after further adjusting for the Org 10 172 test in the Treatment of Acute Stroke classification (<24 hours: adjusted HR, 1.51 [95% CI, 1.01-2.27]; P = 0.05; 24-72 hours: adjusted HR, 1.55 [95% CI, 1.14-2.10]; P = 0.01). The association only existed in patients with large-artery atherosclerosis (adjusted HR, 1.68 [95% CI, 1.06-2.64]; P = 0.03). However, the association was not found in the hsCRP level measured between 72 hours and 8 days. Similar results were found for the outcome of combined vascular events. Additionally, hsCRP levels measured between 24 and 72 hours were associated with an increased risk of poor functional outcomes. Conclusions Elevated levels of hsCRP measured in the first 72 hours after ischemic stroke or transient ischemic attack but not 72 hours to 8 days, were associated with an increased risk of 1-year stroke recurrence.

Dataset Information

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

Publications

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

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