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Inflammatory risk factors, biomarkers and associated therapy in ischaemic stroke

Nature Reviews Neurology volume 12, pages 594–604 (2016)Cite this article

Subjects

Key Points

  • The risk of ischaemic stroke is associated with systemic inflammation and inflammatory biomarkers, suggesting a causal relationship

  • Acute infections activate the inflammatory cascade, which might increase the subsequent risk of stroke

  • Chronic infection and infectious burden have been associated with an increased risk of stroke

  • Various inflammatory mechanisms probably have different roles in different subtypes of stroke

  • C-Reactive protein, IL-6 and lipoprotein-associated phospholipase A2 are indicators of chronic inflammation and might be biomarkers of stroke risk

  • Various general and targeted therapeutic strategies that aim to decrease the risk of stroke by reducing inflammation have been studied and remain under investigation

Abstract

Proinflammatory conditions, including acute and chronic infections, have been associated with an increased risk of stroke. The risk of stroke is increased by both the acute and chronic phases of a wide spectrum of proinflammatory conditions, suggesting that the association is related to activation of the inflammatory response rather than the condition itself. Different inflammatory mechanisms probably influence the risk of different stroke subtypes. This hypothesis is supported by observations that high levels of various immune system markers and acute phase reactants in otherwise healthy individuals have also been associated with ischaemic stroke subtypes. C-reactive protein, IL-6 and lipoprotein-associated phospholipase A2 are some of the inflammatory markers that have been associated with stroke risk and prognosis. Multiple epidemiological studies have demonstrated that these markers are associated with the risk of stroke, but the value of these markers in a clinical setting has not yet been proven. Further research is needed to determine whether immune system modulators can lower the risk of stroke in individuals with elevated concentrations of inflammatory markers. Here, we review the association between infection, systemic inflammation, and ischaemic stroke, and discuss the currently recommended preventive methods to decrease the risk of stroke associated with systemic inflammation.

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Figure 1: The contribution of inflammation to the development of an atherosclerotic plaque.
Figure 2: The proposed role of infection and inflammation in acute ischaemic stroke.
Figure 3: Association between acute infection and stroke risk.

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Acknowledgements

The authors acknowledge funding support for work described in this review from the National Institute of Neurological Disorders and Stroke (NINDS R01 NS29993, R01 NS050724, T32 NS07153); the Bristol-Myers Squibb–Sanofi Partnership and diaDexus; and the American Heart Association (Grant-in-Aid 0355596T; Kathleen Scott Fellowship).

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  1. Department of Neurology, College of Physicians and Surgeons, Columbia University, Neurological Institute, 710 West 168th Street, New York, 10032, New York, USA

    Charles C. Esenwa & Mitchell S. Elkind

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C.C.E. researched data for the article. Both authors wrote the article, made substantial contributions to discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Mitchell S. Elkind.

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Competing interests

M.S.E received research support from the Bristol-Myers Squibb–Sanofi Partnership and diaDexus, Inc.; royalties from UpToDate for chapters related to cryptogenic stroke and hemicraniectomy; receives compensation for providing consultative services for Biotelemetry (Cardionet), the Bristol-Myers Squibb–Pfizer Partnership, Boehringer–Ingelheim, and the Sanofi–Regeneron Partnership; serves as the lead Principal Investigator for a Biogen IDEC study of Tysabri® and stroke; and has given expert legal opinions on behalf of Merck (NuvaRing® and stroke litigation), BMS-Sanofi Pharmaceutical Partnership (clopidogrel and stroke litigation), and Hi-Tech Pharmaceuticals (dimethylamylamine and stroke litigation). C.C.E. declares no competing interests.

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Acute phase reactants

Serum proteins whose concentrations increase as a result of an acute inflammatory state.

Arterial dolichoectasia

Pathological dilation and elongation of arteries through chronic vessel wall remodelling.

Lacunar strokes

Occlusions of a deep penetrating artery leading to infarction of a relatively small cerebral territory.

Mendelian randomization

The random assortment of genetic alleles in a person or a population that can be used as a method to study the risk of having that allele.

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Esenwa, C., Elkind, M. Inflammatory risk factors, biomarkers and associated therapy in ischaemic stroke. Nat Rev Neurol 12, 594–604 (2016). https://doi.org/10.1038/nrneurol.2016.125

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