+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis



Blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-lacunar stroke and non-stroke: systematic review and meta-analysis



Cerebrovascular Diseases 37(1): 64-75



The cause of cerebral small vessel disease is not fully understood, yet it is important, accounting for about 25% of all strokes. It also increases the risk of having another stroke and contributes to about 40% of dementias. Various processes have been implicated, including microatheroma, endothelial dysfunction and inflammation. A previous review investigated endothelial dysfunction in lacunar stroke versus mostly non-stroke controls while another looked at markers of inflammation and endothelial damage in ischaemic stroke in general. We have focused on blood markers between clinically evident lacunar stroke and other subtypes of ischaemic stroke, thereby controlling for stroke in general. We systematically assessed the literature for studies comparing blood markers of coagulation, fibrinolysis, endothelial dysfunction and inflammation in lacunar stroke versus non-stroke controls or other ischaemic stroke subtypes. We assessed the quality of included papers and meta-analysed results. We split the analysis on time of blood draw in relation to the stroke. We identified 1,468 full papers of which 42 were eligible for inclusion, including 4,816 ischaemic strokes, of which 2,196 were lacunar and 2,500 non-stroke controls. Most studies subtyped stroke using TOAST. The definition of lacunar stroke varied between studies. Markers of coagulation/fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), fibrinogen, D-dimer) were higher in lacunar stroke versus non-stroke although fibrinogen was no different to non-stroke in the acute phase. tPA and PAI were no different between lacunar and non-lacunar stroke. Fibrinogen and D-dimer were significantly lower in lacunar stroke compared to other ischaemic strokes, both acutely and chronically. Markers of endothelial dysfunction (homocysteine, von Willebrand Factor (vWF), E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM), vascular cellular adhesion molecule-1 (VCAM)) were higher or had insufficient or conflicting data (P-selectin, VCAM) in lacunar stroke versus non-stroke. Compared to other ischaemic stroke subtypes, homocysteine did not differ in lacunar stroke while vWF was significantly lower in lacunar stroke acutely [atherothrombotic standardized mean difference, SMD, -0.34 (-0.61, -0.08); cardioembolic SMD -0.38 (-0.62, -0.14)], with insufficient data chronically. Markers of inflammation (C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)) were higher in lacunar stroke versus non-stroke, although there were no studies measuring TNF-α chronically and the sole study measuring IL-6 chronically showed no difference between lacunar stroke and non-stroke. Compared to other ischaemic stroke subtypes, there was no difference (CRP) or insufficient or conflicting data (TNF-α) to lacunar stroke. IL-6 was significantly lower [atherothrombotic SMD -0.37 (-0.63, -0.10); cardioembolic SMD -0.52 (-0.82, -0.22)] in lacunar stroke acutely, with insufficient data chronically. Lacunar stroke is an important stroke subtype. More studies comparing lacunar stroke to non-lacunar stroke specifically, rather than to non-stroke controls, are needed. Prospective studies with measurements taken well after the acute event are more likely to be helpful in determining pathogenesis. The available data in this review were limited and do not exclude the possibility that peripheral inflammatory processes including endothelial dysfunction are associated with lacunar stroke and cerebral small vessel disease.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 051835420

Download citation: RISBibTeXText

PMID: 24401164

DOI: 10.1159/000356789


Related references

Blood markers of inflammation and endothelial dysfunction in cardioembolic stroke: systematic review and meta-analysis. Biomarkers 22(3-4): 200-209, 2017

Cognitive impairment after lacunar stroke: systematic review and meta-analysis of incidence, prevalence and comparison with other stroke subtypes. Journal of Neurology, Neurosurgery, and Psychiatry 84(8): 893-900, 2013

Endothelial dysfunction in lacunar stroke: a systematic review. Cerebrovascular Diseases 27(5): 519-526, 2009

A systematic review of dynamic cerebral and peripheral endothelial function in lacunar stroke versus controls. Stroke 41(6): E434-E442, 2010

Systematic review and meta-analysis of interventions tested in animal models of lacunar stroke. Stroke 45(2): 563-570, 2014

Lacunar syndromes, small deep infarcts, and final diagnosis of lacunar stroke mechanism The Northern Manhattan Stroke Study. Stroke 28(1): 235, 1997

Family history of stroke is an independent risk factor for lacunar stroke subtype with asymptomatic lacunar infarcts at younger ages. Stroke 42(5): 1196-1200, 2011

Metabolic syndrome relates to lacunar stroke without white matter lesions: a study in first-ever lacunar stroke patients. Cerebrovascular Diseases 29(5): 503-507, 2010

Distinct non-cerebrovascular risk factors for ischemic lacunar stroke and non-lacunar stroke: preliminary results. Genetics and Molecular Research 14(2): 3170-3176, 2016

Coagulation - fibrinolysis abnormilites in lacunar stroke. European Journal of Neurology 10(Suppl. 1): 236, 2003

Admission markers predict lacunar and non-lacunar stroke in young patients. Thrombosis Research 128(1): 14-17, 2011

Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review. Medical Science Monitor Basic Research 23: 97-140, 2017

A raging fire in acute lacunar stroke: inflammation, blood-brain barrier dysfunction and the origin of cerebral microbleeds. Journal of the Neurological Sciences 340(1-2): 1-2, 2014

C-reactive protein as a prognostic marker after lacunar stroke: levels of inflammatory markers in the treatment of stroke study. Stroke 45(3): 707-716, 2014

ACP Journal Club: review: in lacunar stroke, single antiplatelet therapy reduces recurrent stroke more than placebo. Annals of Internal Medicine 163(4): Jc6-Jc6, 2015