The role of high-sensitivity C-reactive protein serum levels in the prognosis for patients with stroke: a meta-analysis

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The role of high-sensitivity C-reactive protein serum levels in the prognosis for patients with stroke: a meta-analysis

Liuting Chen¹, Min Wang¹, Chanrui Yang¹, Yefei Wang¹ and Bonan Hou^2*

• ¹The Second Clinical Medical College, Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China
• ²Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, Hangzhou, China

Background: The impact of high-sensitivity C-reactive protein (hs-CRP) as a biomarker of inflammation on the prognosis of stroke patients remains controversial, this study was conducted to evaluate the prognostic value of hs-CRP levels for patients with stroke.

Methods: PubMed, Web of Science, Embase, and Cochrane Library databases were searched from inception to October 28, 2022. Outcome measures were all-cause mortality, recurrent stroke, and poor prognosis. The relationship between the highest versus lowest levels of hs-CRP or per unit increment and outcomes as measured by risk ratio (RR) and corresponding 95% confidence intervals (CI).

Results: A total of 39 articles were eligible for meta-analysis. High hs-CRP levels at admission were associated with mortality among patients with acute ischemic stroke (AIS) [RR = 3.84, 95% CI (2.41 ~ 6.111); p < 0.001], risk of recurrent stroke [RR = 1.88, 95%CI (1.41 ~ 2.52); p < 0.001], and poor prognosis [RR = 1.77, 95% CI (1.59 ~ 1.97); p < 0.001]. The risk ratios for the association of per unit increase in hs-CRP levels with mortality, risk of recurrent stroke, and poor prognosis were as follows, respectively: 1.42 [95% CI (1.19–1.69); p < 0.001], 1.03 [95% CI (1.01–1.04); p = 0.003], and 1.27 [95% CI (1.10–1.47); p = 0.001]. For hemorrhagic stroke (HS), the risk ratios (RR) for the highest versus the lowest (reference) category of hsCRP or per unit increment to all-cause mortality were 4.36 [95% CI (1.38–13.73); p = 0.012] and 1.03 [95% CI (0.98–1.08); p = 0.238].

Conclusion: Hs-CRP levels are strongly associated with mortality, risk of stroke recurrence and poor prognosis in stroke patients. Therefore, hs-CRP levels may contribute to the prognosis prediction of these patients.

1. Introduction

Stroke is the second leading cause of death following ischemic heart disease, accounting for 11.6% of total deaths (1). Particularly, ischemic stroke (IS) makes up around 87% of stroke cases (2). In China, the burden of stroke data in 2020 revealed that the number of deaths related to stroke reached a staggering 2.3 million (3). The wide application of modern secondary prevention therapy may be counterbalanced by a high risk of further vascular events in stroke survivors (4) which has become an increasing burden on public health worldwide. Therefore, it is of great significance to explore key factors affecting the prognosis of patients with stroke to formulate appropriate treatment regimens and optimize healthcare for these patients.

The pathogenesis of stroke mainly includes oxidative stress and inflammation. Inflammatory factors can not only induce cell death responsible for functional injury (5), but also underlie the development of atherosclerosis by regulating macrophages, cytokines, and leukocyte adhesion molecules to induce endothelial dysfunction, plaque formation and rupture, platelet aggregation, and thrombosis (6, 7). Therefore, some inflammatory cytokines are investigated as predictors of functional outcomes after stroke (8).

High-sensitivity C-reactive protein (hs-CRP), which is synthesized and secreted by liver cells, is considered a non-specific biomarker of inflammation (9). Previous meta-analyses have shown that hs-CRP can be used to predict the prognosis of patients with COVID-19 (10), type 2 diabetes (11), or coronary artery disease (12), and they also indicate that the level of hs-CRP is an independent risk factor for different types of stroke (13). However, its use as a biomarker to predict patient prognosis after stroke remains controversial. Zeng et al. (14) showed that a high level of hs-CRP level was an independent predictor of adverse clinical outcomes in patients with stroke. Zhang et al. (15) pointed out that the risk of recurrent stroke in patients with IS increased by 22% with a per unit increase in the level of hs-CRP. However, some studies suggest that elevated hs-CRP levels do not seem to independently affect the outcome in patients with stroke (16).

Furthermore, previous meta-analyses have only focused on the impact of hs-CRP on the mortality (17) or stroke recurrence (18) prognosis of ischemic stroke patients, without considering the overall mortality prognosis of hemorrhagic stroke patients, and lacking analysis of poor outcomes based on mRS scores. Therefore, the present study aims to comprehensively evaluate the prognostic value of hs-CRP levels for patients with stroke by performing a meta-analysis to investigate the correlation between hs-CRP levels with recurrent stroke, mortality, and poor prognosis in patients with ischemic or hemorrhagic stroke.

 

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