Hs-CRP in stroke: A meta-analysis

doi:10.1016/j.cca.2015.11.027

Clinica Chimica Acta

Volume 453, 30 January 2016, Pages 21-27

https://doi.org/10.1016/j.cca.2015.11.027 Get rights and content

Highlights

•
Conflicting results have been reported on hs-CRP and risk of different types of strokes.
•
Individuals with elevated hs-CRP level had 46% excessive risk of ischemic stroke.
•
Subjects with elevated hs-CRP level showed some trend to reduce hemorrhagic stroke risk.
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Association between hs-CRP level and ischemic stroke risk was more pronounced in men.

Abstract

Background

Studies on high-sensitivity C-reactive protein (hs-CRP) and stroke risk have yielded conflicting results.

Objective

To determine whether elevated baseline hs-CRP presents an independent risk for different kinds of strokes by conducting a meta-analysis.

Methods

The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases were systematically searched for prospective observational studies published until January 2015. Studies reporting hs-CRP levels and adjusted risk estimates of different stroke subtypes by hs-CRP were selected. Pooled results were expressed as adjusted risk ratios (RRs), with corresponding 95% confidence intervals (CI) for the highest versus the lowest hs-CRP category.

Results

Twelve studies involving 2269 strokes, of which 2436 were ischemic and 655 were hemorrhagic, were identified from 66,560 participants. When comparing the highest with the lowest hs-CRP category, the pooled RR of ischemic strokes was 1.46 (95% CI 1.27–1.67) in a fixed-effect model. The pooled RRs of all strokes and hemorrhagic stroke were 1.23 (95% CI: 0.997–1.51) and 0.82 (95% CI 0.59–1.13), respectively. The risk of ischemic strokes seemed higher in men (RR 1.66; 95% CI 1.23–2.24).

Conclusions

Elevated baseline hs-CRP levels are independently associated with excessive ischemic stroke risk but exhibit no clear effect on hemorrhagic stroke.

Introduction

Stroke has been identified as the main cause of mortality and disability worldwide [1]. Stroke can be classified into ischemic and hemorrhagic strokes, in accordance with its underlying pathology. About 15 million people suffer from stroke annually [2] of which 87% comprises ischemic stroke [3]. Stroke risk prediction based on conventional risk factors such as blood pressure, diabetes and dyslipidemia remains inadequate. Identification of novel predictive biomarkers would contribute to risk prediction in subjects at the risk of developing stroke.

Inflammation plays an important role in the development of atherosclerosis [4], [5]. C-reactive protein (CRP), an acute-phase reactant produced by hepatocytes, is considered a biomarker of inflammation. Meanwhile, hs-CRP accurately detects low-grade inflammation [6]. Measurement of CRP using high-sensitivity CRP (hs-CRP) assays is widely used in clinical practice, particularly in cardiovascular disease (CVD) risk stratification [7]. A high-level CRP, measured by hs-CRP, has been proposed as a risk factor for ischemic stroke or total stroke [8], [9], [10], [11], [12], [13], [14] in some but not all populations [15], [16], [17], [18], [19]. The conflicting results could be linked to the population studied, with ethnicities, age or gender difference considered [20], [21]. Previous meta-analysis conducted by The Emerging Risk Factors Collaboration suggested that a 1-SD increment in CRP was associated with 46% and 39% greater risk of ischemic stroke and all strokes [22]. A meta-analysis based on the cutoff value of hs-CRP can elucidate the prognostic role of hs-CRP in stroke.

This meta-analysis aims to quantitatively estimate the elevated baseline serum hs-CRP as the cutoff value and the risk of different types of strokes on the basis of a prospective observational study.

Section snippets

Search strategy

This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement [23].We searched online electronic databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from inception to January 2015, with the languages limited to English and Chinese. Potentially relevant studies were identified by the following MeSH terms: ‘C-reactive protein’ OR ‘high-sensitivity CRP’ OR

Literature search

A total of 518 publications were identified from the initial search. After screening the titles and abstracts, 486 records were excluded. Thirty-two full-texts were determined for a thorough assessment. Twenty papers were further excluded. Finally, 12 studies [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19] satisfied the inclusion criteria (Fig. 1).

Study characteristics

The characteristics of the included studies are shown in Table 1. Twelve studies with 66,560 participants were identified. Of

Discussion

The findings of our meta-analysis suggested that an elevated hs-CRP level was associated with an increased risk of ischemic strokes. Subjects exhibiting the highest hs-CRP levels had a 46% greater risk of ischemic stroke; however, no clear effect on hemorrhagic stroke risk prediction was indicated. The risk of ischemic strokes seemed more pronounced in men.

Our study supported the findings of the previous meta-analysis [22]. This meta-analysis found that a per-SD increase in CRP was associated

Conflict of interest

There are no conflicts of interest for any of the authors.

Acknowledgments

This study was supported by the Key R & D special fund of Jiangsu Province (BE2015666).

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View full text

Hs-CRP in stroke: A meta-analysis

Highlights

Abstract

Background

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Search strategy

Literature search

Study characteristics

Discussion

Conflict of interest

Acknowledgments

Lancet

Neuropharmacology

Am. J. Emerg. Med.

Atherosclerosis

Am. J. Prev. Med.

Ann. Epidemiol.

J. Stroke Cerebrovasc. Dis.

Curr. Opin. Pharmacol.

Int. J. Cardiol.

Lancet

Nutr. Metab. Cardiovasc. Dis.

Inflammation in atherosclerosis

Nature

An update on the role of markers of inflammation in atherosclerosis

J. Atheroscler. Thromb.

The use of high-sensitivity assays for C-reactive protein in clinical practice

Nat. Clin. Pract. Cardiovasc. Med.

Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association

Circulation

Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men

N. Engl. J. Med.

C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study

Circulation

Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study

Arch. Intern. Med.

C-reactive protein and prediction of coronary heart disease and global vascular events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

Circulation

Relative value of inflammatory, hemostatic, and rheological factors for incident myocardial infarction and stroke: the Edinburgh Artery Study

Circulation

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Cerebrovasc. Dis.