WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTStroke is the largest single cause of disability in the UK. While tests based upon biomarkers have been around for decades, interest in the applications of biomarkers has increased greatly in recent years. Biomarkers released into the bloodstream following a stroke are useful not only for understanding the pathogenesis of stroke, but also play a significant role in the development of personalised medicine. The efficacy of current clinical models and imaging techniques for the diagnosis and prognosis of acute stroke could be improved when used in conjunction with blood biomarkers. While several studies have proposed a number of biomarkers associated with acute stroke in humans, there is conflicting information about the significance of implicated markers, and their clinical relevance is unclear. WHAT THIS STUDY ADDSIn an attempt to consolidate the plethora of data in this field, we have conducted a comprehensive systematic review and meta-analysis of proteomic and metabolomic blood biomarkers associated with acute stroke. Our meta-analysis has found eight biomarkers that are significantly associated with the diagnosis and prognosis of acute stroke. Interestingly we also found that CRP, a protein commonly implicated as a strong biomarker of inflammation and stroke, may not have sufficient sensitivity and specificity to be of clinical value, Thus while the biomarkers identified through our study are likely to be biologically informative about the mechanisms of vascular disease, their clinical potential for a blood-based test warrants further investigation. AIMSIdentification of biomarkers for stroke will aid our understanding of its aetiology, provide diagnostic and prognostic indicators for patient selection and stratification, and play a significant role in developing personalized medicine. We undertook the largest systematic review conducted to date in an attempt to characterize diagnostic and prognostic biomarkers in acute ischaemic and haemorrhagic stroke and those likely to predict complications following thrombolysis. METHODSA comprehensive literature search was carried out to identify diagnostic and prognostic stroke blood biomarkers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for each biomarker. RESULTSWe identified a total of 141 relevant studies, interrogating 136 different biomarkers. Three biomarkers (C-reactive protein, P-selectin and homocysteine) significantly differentiated between ischaemic stroke and healthy control subjects. Furthermore, glial fibrillary acidic protein levels were significantly different between haemorrhagic stroke and ischaemic stroke patients (MD 224.58 ng l -1 ; 95% CI 25.84, 423.32; P = 0.03), high levels of admission glucose were a strong predictor of poor prognosis after ischaemic stroke and symptomatic intracerebral haemorrhage post-thrombolysis, glutamate was found to be an indicator of progressive (unstable) stroke (MD 172.65 mmol l -1 , 95% CI 130.54, 214.75; P = 0.00001), D-dimer predicted in-hospi...

Background and Purpose-Quantitative predictions of the risk of cerebral venous thrombosis (CVT) conferred by certaingenotypes have yet to be reliably established. We conducted a comprehensive meta-analysis of all candidate genes studied to assess their genetic contribution to the etiology of CVT. We compared our findings against equivalent analyses for pediatric CVT and adult ischemic stroke. Methods-Databases were searched to August 2010 for all genes investigated in adult CVT, and odds ratios (ORs) for each gene-disease association were calculated. A mendelian randomization strategy was also undertaken to determine whether a causal relation to one gene could be ascertained. Results-We identified 26 case-control studies investigating 6 polymorphisms in 6 genes and included 1183 CVT cases and 5189 controls. Statistically significant associations with CVT were found for factor V Leiden/G1691A (ORϭ2.

ObjectiveFollowing an acute stroke, there is a high risk of recurrence. However, the leading cause of mortality following a stroke is due to coronary artery disease (CAD) and myocardial infarction (MI) but that risk has not been robustly quantified. We sought to reliably quantify the risk of ischaemic heart disease (IHD) in patients presenting with acute ischaemic stroke (AIS) in the absence of a known cardiac history.SettingA meta-analysis study. PubMed, MEDLINE, EMBASE and Google Scholar were searched for potential studies up to October 2015. Included studies reported an acute cerebral ischaemic event and followed for CAD or MI within 1 year in patients without known IHD. Using arcsine transformed proportions for meta-analysis, studies were combined using a generic inverse variance random-effects model to calculate the pooled standardised mean difference and 95% CIs. These were interpreted as the percentage prevalence of CAD or incidence of MI following AIS.Results17 studies with 4869 patients with AIS demonstrated a mean average of asymptomatic CAD in 52%. Anatomical methods of CAD detection revealed a prevalence of asymptomatic ≥50% coronary stenosis in 32% (95% CI 19% to 47%; p<0.00001). 8 studies with 47229 patients with ischaemic stroke revealed an overall risk of MI in the year following stroke of 3% (95% CI 1% to 5%; p<0.00001) despite the absence of any cardiac history.ConclusionsOne-third of patients with ischaemic stroke with no cardiac history have more than 50% coronary stenosis and 3% are at risk of developing MI within a year. Our findings provide a reliable quantitative measure of the risk of IHD following AIS in patients with no cardiac history.

The burden of stroke is disproportionately high in the South Asian subcontinent with South Asian ethnicity conferring a greater risk of ischemic stroke than European ancestry regardless of country inhabited. While genes associated with stroke in European populations have been investigated, they remain largely unknown in South Asians. We conducted a comprehensive meta-analysis of known genetic polymorphisms associated with South Asian ischemic stroke, and compared effect size of the MTHFR C677T-stroke association with effect sizes predicted from homocysteine-stroke association. Electronic databases were searched up to August 2012 for published case control studies investigating genetic polymorphisms associated with ischemic stroke in South Asians. Pooled odds ratios (OR) for each gene-disease association were calculated using a random-effects model. We identified 26 studies (approximately 2529 stroke cases and 2881 controls) interrogating 33 independent genetic polymorphisms in 22 genes. Ten studies described MTHFR C677T (108 with TT genotype and 2018 with CC genotype) -homocysteine relationship and six studies (735 stroke cases and 713 controls) described homocysteine-ischemic stroke relationship. Risk association ORs were calculated for ACE I/D (OR 5.00; 95% CI, 1.17–21.37; p = 0.03), PDE4D SNP 83 (OR 2.20; 95% CI 1.21–3.99; p = 0.01), PDE4D SNP 32 (OR 1.57; 95% CI 1.01–2.45, p = 0.045) and IL10 G1082A (OR 1.44; 95% CI, 1.09–1.91, p = 0.01). Significant association was observed between elevated plasma homocysteine levels and MTHFR/677 TT genotypes in healthy South Asians (Mean difference (ΔX) 5.18 µmol/L; 95% CI 2.03–8.34: p = 0.001). Our results demonstrate that the genetic etiology of ischemic stroke in South Asians is broadly similar to the risk conferred in Europeans, although the dataset is considerably smaller and warrants the same clinical considerations for risk profiling.

No abstract