Elsevier

Clinica Chimica Acta

Volume 413, Issues 23–24, 20 November 2012, Pages 1861-1865
Clinica Chimica Acta

The association of statin therapy and high-sensitivity C‐reactive protein level for predicting clinical outcome in acute non-cardioembolic ischemic stroke

https://doi.org/10.1016/j.cca.2012.07.021Get rights and content

Abstract

Background

Statins reportedly have anti-inflammatory effects aside from their cholesterol-lowering effect. We investigated the effects of statins on serum hs-CRP level and clinical outcome of acute ischemic stroke (IS) patients.

Methods

This prospective cohort study consequently evaluated patients with acute IS in a single medical center. Serum hs-CRP levels were measured at different time points (within 48 h and 30 days post-stroke). The patients' clinical and laboratory data on admission were analyzed.

Results

Total 100 patients with acute IS were divided in the statin group (n = 50) and the non-statin group (n = 50). Serum hs-CRP level was similar in the 2 groups within 48 h after acute IS, but was significantly lower in the statin group on Day 30 compared to the non-statin group (p < 0.05). The statin group also had favorable 3-month outcome compared to the non-statin group (p < 0.05). After adjustments for covariance using stepwise logistic regression, only NIHSS on admission (OR = 1.38, 95% CI = 1.06–1.80; p = 0.02) and hs-CRP in the acute phase (OR = 1.74, 95% CI = 1.30–2.33; p = 0.001) were significantly and independently predictive of 3-month outcome.

Conclusion

Statin therapy reduces serum hs-CRP level and may be associated with favorable 3-month outcome in patients after acute IS.

Highlights

► Statin therapy alters serum hs-CRP level in patient after acute ischemic stroke. ► Statin treatment is associated with good outcome after acute ischemic stroke. ► The hs-CRP level after ischemic stroke is a predictive factor of 3-month outcome.

Introduction

Inflammation plays an important role in the pathogenesis of acute ischemic stroke (IS) [1]. Previous researches suggest that post-stroke inflammatory responses may exacerbate tissue damage after cerebral infarction and contribute to the clinical outcome [2], [3]. Measuring the inflammatory biomarkers that reflect the degree of inflammation may help predict future cardiovascular event after acute IS. Although many inflammatory biomarkers have been reported to be useful in predicting clinical outcome after stroke [4], [5], [6], high-sensitivity C-reactive protein (hs-CRP) remains one of the most widely used in clinical practice [7], [8].

Statins, a 3-hydroxy 3-methyl-glutaryl coenzyme-A reductase inhibitor, is originally used as treatment of hypercholesterolemia [9]. Increasing evidence reveals that statins have anti-inflammatory effects in addition to their cholesterol-lowering effect [10], [11]. Statin therapy has been shown to reduce the severity of acute IS and improve its outcome [12], [13], [14], [15]. The JUPITER Study further demonstrates the primary prevention effect of rosuvastatin in apparently healthy persons without hyperlipidemia but with elevated hs-CRP levels [16].

A recent study reports that statin therapy is associated with reduced platelet activity and favorable clinical outcome in patients after acute IS [17]. However, the study does not show the effects of statins on serum hs-CRP level after IS. Therefore, this prospective cohort study aimed to examine the role serum hs-CRP levels in predicting the outcome of IS patients and the impact of statin therapy on serum hs-CRP level and its clinical outcome.

Section snippets

Study participants

Consecutive acute non-cardioembolic IS patients, age between 18 and 80 y, who were admitted to the Neurology Department of Chang Gung Memorial Hospital-Kaohsiung from July 2010 to June 2011 were evaluated. Acute IS was defined as acute onset loss of focal cerebral function persisting for at least 24 h. The diagnosis of stroke was based on clinical presentation, neurologic examination, and results of brain magnetic resonance imaging (MRI) with diffusion-weighted images (DWI). The etiologic

Baseline characteristics between the patient groups

Of the 50 patients in the statin group, 16 used atorvastatin (6 cases with 40 mg/day and 10 cases with 10 mg/day), 10 fluvastatin (80 mg/day), 16 rosuvastatin (14 cases with 10 mg/day and 2 cases with 5 mg/day), and 8 simvastatin (6 cases with 40 mg/day and 2 cases with 20 mg/day). They took their first dose of statin within 72 h after the onset of stroke. The other 50 patients did not receive statin therapy (non-statin group) before and after the stroke event. Based on the demographic data of the

Discussion

The present study has 3 major findings. First, statin therapy significantly alters serum hs-CRP level in patient after acute IS. Second, patients with statin therapy after acute IS have a higher percentage of good prognosis. Third, hs-CRP level during acute phase of IS (within 48 h) is significantly and independently predictive of the three-month outcome.

As an inflammatory biomarker, hs-CRP independently predicts future cardiovascular events and stroke regardless of low-density lipoprotein

Acknowledgments

This study was supported by grants from the Chang Gung Memorial Hospital Research Project (CMRPG881011) and the National Science Council Research Project (99-2314-B-182-055-MY2). We wish to thank Y.F. Chiang for her valuable technical assistance. Doctor Gene Alzona Nisperos provided language help and writing assistance for this manuscript.

References (32)

  • C.J. Frijns et al.

    Inflammatory cell adhesion molecules in ischemic cerebrovascular disease

    Stroke

    (2002)
  • A.W. Alberts

    Discovery, biochemistry and biology of lovastatin

    Am J Cardiol

    (1988)
  • D.J. Lefer

    Statins as potent antiinflammatory drugs

    Circulation

    (2002)
  • B.R. Kwak et al.

    Statins inhibit leukocyte recruitment: new evidence for their anti-inflammatory properties

    Arterioscler Thromb Vasc Biol

    (2001)
  • M. Moonis et al.

    HMG-CoA reductase inhibitors improve acute ischemic stroke outcome

    Stroke

    (2005)
  • P. Amarenco et al.

    Effects of intense low-density lipoprotein cholesterol reduction in patients with stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

    Stroke

    (2007)
  • Cited by (25)

    • Genetic polymorphisms of MiR-499a (rs3746444) and MiR-196a2 (rs11614913) in ischemic stroke and correlation with risk factors

      2022, Gene Reports
      Citation Excerpt :

      It seemed that miR-499a could influence ischemic stroke by regulating inflammation, fibrinogen, and C-reacting protein (Yang et al., 2012). Another study suggested that patients with the AG and GG genotypes of miR-499a had increased plasma/serum concentrations of C-reacting protein that could result in increased blood pressure, Body Mass Index (BMI), triglycerides, and insulin resistance, while AA carriers had lower C-reacting protein concentrations (Tsai et al., 2012; Luo et al., 2017). With respect to miR-196a2 T>C, the TT genotypes had a protective role against ischemic stroke, while the CC genotypes were associated with an increased risk of ischemic stroke.

    • High-sensitivity C-reactive protein in stroke patients – The importance in consideration of influence of multiple factors in the predictability for disease severity and death

      2017, Journal of Clinical Neuroscience
      Citation Excerpt :

      Although many inflammatory biomarkers have been reported to be useful in predicting clinical outcome after stroke, hsCRP remains one of the most widely used in clinical practice [8–12]. Increased hsCRP has been associated with the development of atherosclerosis, ischaemic attacks, hemorrhagic stroke, as well as disease outcomes [13–17]. Studies suggest that post-stroke inflammatory responses may exacerbate tissue damage after cerebral infarction and affect clinical outcomes [18,19].

    View all citing articles on Scopus
    1

    Contributed equally to this work.

    View full text