Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.
Ontology highlight
ABSTRACT:
SUBMITTER: Abraham G
PROVIDER: S-EPMC6925280 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Genomic risk score offers predictive performance comparable to clinical risk factors for ischaemic stroke.
Abraham Gad G Malik Rainer R Yonova-Doing Ekaterina E Salim Agus A Wang Tingting T Danesh John J Butterworth Adam S AS Howson Joanna M M JMM Inouye Michael M Dichgans Martin M
Nature communications 20191220 1
Recent genome-wide association studies in stroke have enabled the generation of genomic risk scores (GRS) but their predictive power has been modest compared to established stroke risk factors. Here, using a meta-scoring approach, we develop a metaGRS for ischaemic stroke (IS) and analyse this score in the UK Biobank (n = 395,393; 3075 IS events by age 75). The metaGRS hazard ratio for IS (1.26, 95% CI 1.22-1.31 per metaGRS standard deviation) doubles that of a previous GRS, identifying a subset ...[more]
Similar Datasets
Project description:We aimed to predict obesity risk with genetic data, specifically, obesity-associated gene expression profiles. Genetic risk score was computed. The genetic risk score was significantly correlated with BMI when an optimization algorithm was used. Linear regression and built support vector machine models predicted obesity risk using gene expression profiles and the genetic risk score with a new mathematical method.
2018-01-25 | GSE109597 | GEO
Project description:Age dependency of acute ischaemic stroke aetiology and vascular risk factors have not been adequately evaluated in stroke patients in Norway. Aims of this study were to evaluate how stroke subtypes and vascular risk factors vary with age in a western Norway stroke population.Patients aged 15-100 years consecutively admitted to our neurovascular centre with acute ischaemic stroke between 2006 and 2012 were included. The study population was categorized as young (15-49 years), middle-aged (50-74 years) or elderly (≥ 75 years). Stroke aetiology was defined by TOAST criteria. Risk factors and history of cardiovascular disease were recorded.In total, 2484 patients with acute cerebral infarction were included: 1418 were males (57.3%). Mean age was 70.8 years (SD ± 14.9), 228 patients were young, 1126 middle-aged, and 1130 were elderly. The proportion of large-artery atherosclerosis and of small-vessel occlusion was highest among middle-aged patients. The proportion of cardioembolism was high at all ages, especially among the elderly. The proportion of stroke of other determined cause was highest among young patients. Some risk factors (diabetes mellitus, active smoking, angina pectoris, prior stroke and peripheral artery disease) decreased among the elderly. The proportions of several potential causes increased with age.The proportion of stroke subtypes and vascular risk factors are age dependent. Age 50-74 years constitutes the period in life where cardiovascular risk factors become manifest and stroke subtypes change.
| S-EPMC4744685 | biostudies-other
Project description:BackgroundA third of transient ischaemic attacks (TIAs) and ischaemic strokes are of undetermined cause (ie, cryptogenic), potentially undermining secondary prevention. If these events are due to occult atheroma, the risk-factor profile and coronary prognosis should resemble that of overt large artery events. If they have a cardioembolic cause, the risk of future cardioembolic events should be increased. We aimed to assess the burden, outcome, risk factors, and long-term prognosis of cryptogenic TIA and stroke.MethodsIn a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from April 1, 2002, to March 31, 2014, we compared cryptogenic events versus other causative subtypes according to the TOAST classification. We compared markers of atherosclerosis (ie, risk factors, coronary and peripheral arterial disease, asymptomatic carotid stenosis, and 10-year risk of acute coronary events) and of cardioembolism (ie, risk of cardioembolic stroke, systemic emboli, and new atrial fibrillation [AF] during follow-up, and minor-risk echocardiographic abnormalities and subclinical paroxysmal AF at baseline in patients with index events between 2010 and 2014).FindingsAmong 2555 patients, 812 (32%) had cryptogenic events (incidence of cryptogenic stroke 0·36 per 1000 population per year, 95% CI 0·23-0·49). Death or dependency at 6 months was similar after cryptogenic stroke compared with non-cardioembolic stroke (23% vs 27% for large artery and small vessel subtypes combined; p=0·26) as was the 10-year risk of recurrence (32% vs 27%; p=0·91). However, the cryptogenic group had fewer atherosclerotic risk factors than the large artery disease (p<0·0001), small vessel disease (p=0·001), and cardioembolic (p=0·008) groups. Compared with patients with large artery events, those with cryptogenic events had less hypertension (adjusted odds ratio [OR] 0·41, 95% CI 0·30-0·56; p<0·0001), diabetes (0·62, 0·43-0·90; p=0·01), peripheral vascular disease (0·27, 0·17-0·45; p<0·0001), hypercholesterolaemia (0·53, 0·40-0·70; p<0·0001), and history of smoking (0·68, 0·51-0·92; p=0·01), and compared with small vessel and cardioembolic subtypes, they had no excess risk of asymptomatic carotid disease (adjusted OR 0·64, 95% CI 0·37-1·11; p=0·11) or acute coronary events (adjusted hazard ratio [HR] 0·76, 95% CI 0·49-1·18; p=0·22) during follow-up. Compared with large artery and small vessel subtypes combined, patients with cryptogenic events also had no excess of minor-risk echocardiographic abnormalities (cryptogenic 37% vs 45%; p=0·18) or paroxysmal AF (6% vs 10%; p=0·17) at baseline or of new AF (adjusted HR 1·23, 0·78-1·95; p=0·37) or presumed cardioembolic events (1·16, 0·62-2·17; p=0·64) during follow-up.InterpretationThe clinical burden of cryptogenic TIA and stroke is substantial. Although stroke recurrence rates are comparable with other subtypes, cryptogenic events have the fewest atherosclerotic markers and no excess of cardioembolic markers.FundingWellcome Trust, Wolfson Foundation, UK Stroke Association, British Heart Foundation, Dunhill Medical Trust, National Institute for Health Research, Medical Research Council, and the NIHR Oxford Biomedical Research Centre.
| S-EPMC5714616 | biostudies-literature
Project description:IntroductionLiterature on prevalence of symptomatic internal carotid artery stenosis is scarce and heterogeneous. Prevalence may have decreased in recent years due to improved management of cardiovascular risk factors. We aim to estimate current prevalence and identify risk factors of ipsilateral internal carotid artery stenosis in patients with recent hemispheric transient ischaemic attack or ischaemic stroke in the Netherlands.Patients and methodsWe included consecutive adult patients admitted to two large hospitals in the Netherlands in 2014 who suffered from amaurosis fugax, retinal ischaemia, transient ischaemic attack or ischaemic stroke in the vessel territory of the internal carotid artery. Primary outcome was presence of ipsilateral internal carotid artery stenosis (degree subdivided following NASCET criteria), as assessed with duplex ultrasonography, computed tomography angiography and/or magnetic resonance angiography. We used univariable and multivariable logistic regression to identify risk factors for the presence of a 50-100% internal carotid artery stenosis.ResultsWe analysed 883 consecutive patients with recent transient ischaemic attack or ischaemic stroke. Of these, 110 (12.5%) had 50-99% ipsilateral internal carotid artery stenosis. Subgroup analyses showed higher prevalence of any degree of internal carotid artery stenosis for male sex and White patients. In adjusted analyses, higher age (odds ratio 1.4/10 years; 95% confidence interval 1.16-1.63), male sex (odds ratio 2.8; 95% confidence interval 1.83-4.19), retinal ischaemia (odds ratio 2.5; 95% confidence interval 1.32-4.76) and current smoking (odds ratio 1.8; 95% confidence interval 1.09-2.79) were statistically significant risk factors for 50-100% internal carotid artery stenosis.ConclusionThe prevalence of internal carotid artery stenosis seems to be lower in patients with recent transient ischaemic attack or ischaemic stroke than stated in previous studies. We found that higher age, male sex, White ethnicity, retinal ischaemia and current smoking were important risk factors for symptomatic internal carotid artery stenosis.
| S-EPMC7538767 | biostudies-literature
Project description:BACKGROUND:Stroke-associated pneumonia (SAP) is a common complication of cerebrovascular disease. The A2DS2 score has been used to predict the risk of SAP. However, hyperglycemia is not included in this scale. The purpose of the present study was to explore whether the A2DS2 scoring system and hyperglycemia could predict the risk of SAP more effectively than the conventional A2DS2 scale. METHODS:This retrospective study enrolled 2552 patients with acute ischemic stroke. The A2DS2 scores, fasting blood glucose level and blood glucose level on admission were collected. Regression analysis was used to identify the independent risk factors of SAP. ROC curve analysis was used to evaluate the specificity and sensitivity of the combined A2DS2 score and fasting hyperglycemia for predicting SAP. RESULTS:Fasting hyperglycemia was an independent risk factor for SAP (OR?=?2.95; 95% confidence interval: 2.11-4.12; P?< 0.001). The area under curve of the combined A2DS2 score and fasting hyperglycemia was significantly higher than that of the A2DS2 score alone (0.814 vs. 0.793; P?=?0.020). CONCLUSION:Fasting hyperglycemia is an independent risk factor for predicting SAP. Compared with the A2DS2 score, the modified A2DS2 score (combined A2DS2 score and fasting hyperglycemia) is more effective in predicting the risk of SAP.
| S-EPMC6876087 | biostudies-literature
Project description:Hypoxic Ischemic Encephalopathy (HIE) remains a major cause of neurological disability. Early intervention with therapeutic hypothermia improves outcome, but prediction of HIE is difficult and no single clinical marker is reliable. Machine learning algorithms may allow identification of patterns in clinical data to improve prognostic power. Here we examine the use of a Random Forest machine learning algorithm and five-fold cross-validation to predict the occurrence of HIE in a prospective cohort of infants with perinatal asphyxia. Infants with perinatal asphyxia were recruited at birth and neonatal course was followed for the development of HIE. Clinical variables were recorded for each infant including maternal demographics, delivery details and infant's condition at birth. We found that the strongest predictors of HIE were the infant's condition at birth (as expressed by Apgar score), need for resuscitation, and the first postnatal measures of pH, lactate, and base deficit. Random Forest models combining features including Apgar score, most intensive resuscitation, maternal age and infant birth weight both with and without biochemical markers of pH, lactate, and base deficit resulted in a sensitivity of 56-100% and a specificity of 78-99%. This study presents a dynamic method of rapid classification that has the potential to be easily adapted and implemented in a clinical setting, with and without the availability of blood gas analysis. Our results demonstrate that applying machine learning algorithms to readily available clinical data may support clinicians in the early and accurate identification of infants who will develop HIE. We anticipate our models to be a starting point for the development of a more sophisticated clinical decision support system to help identify which infants will benefit from early therapeutic hypothermia.
| S-EPMC8261660 | biostudies-literature
Project description:PurposeNon-adherence to secondary preventative medications after stroke is relatively common and associated with poorer outcomes. Non-adherence can be due to a number of patient, disease, medication or institutional factors. The aim of this review was to identify factors associated with non-adherence after stroke.MethodWe performed a systematic review and meta-analysis of studies reporting factors associated with medication adherence after stroke. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL and Web of Knowledge. We followed PRISMA guidance. We assessed risk of bias of included studies using a pre-specified tool based on Cochrane guidance and the Newcastle-Ottawa scales. Where data allowed, we evaluated summary prevalence of non-adherence and association of factors commonly reported with medication adherence in included studies using random-effects model meta-analysis.FindingsFrom 12,237 titles, we included 29 studies in our review. These included 69,137 patients. The majority of included studies (27/29) were considered to be at high risk of bias mainly due to performance bias. Non-adherence rate to secondary preventative medication reported by included studies was 30.9% (95% CI 26.8%-35.3%). Although many factors were reported as related to adherence in individual studies, on meta-analysis, absent history of atrial fibrillation (OR 1.02, 95% CI 0.72-1.5), disability (OR 1.27, 95% CI 0.93-1.72), polypharmacy (OR 1.29, 95% CI 0.9-1.9) and age (OR 1.04, 95% CI 0.96-1.14) were not associated with adherence.DiscussionThis review identified many factors related to adherence to preventative medications after stroke of which many are modifiable. Commonly reported factors included concerns about treatment, lack of support with medication intake, polypharmacy, increased disability and having more severe stroke.ConclusionUnderstanding factors associated with medication taking could inform strategies to improve adherence. Further research should assess whether interventions to promote adherence also improve outcomes.
| S-EPMC5992740 | biostudies-literature
Project description:BackgroundAs the average life expectancy increases, more people are predicted to have strokes. Recent studies have shown an increasing incidence in certain types of cerebral infarction. We aimed to estimate time trends in incidence, prior risk factors, and use of preventive treatments for ischaemic stroke (IS) aetiological subtypes and to ascertain any demographic disparities.Methods and findingsPopulation-based data from the South London Stroke Register (SLSR) between 2000 and 2015 were studied. IS was classified, based on the underlying mechanism, into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). After calculation of age-, sex-, and ethnicity-specific incidence rates by subtype for the 16-year period, we analysed trends using Cochran-Armitage tests, Poisson regression models, and locally estimated scatterplot smoothers (loess). A total of 3,088 patients with first IS were registered. Between 2000-2003 and 2012-2015, the age-adjusted incidence of IS decreased by 43% from 137.3 to 78.4/100,000/year (incidence rate ratio [IRR] 0.57, 95% CI 0.5-0.64). Significant declines were observed in all subtypes, particularly in SVO (37.4-18; p < 0.0001) and less in CE (39.3-25; p < 0.0001). Reductions were recorded in males and females, younger (<55 years old) and older (≥55 years old) individuals, and white and black ethnic groups, though not significantly in the latter (144.6-116.2; p = 0.31 for IS). A 4-fold increase in prior-to-stroke use of statins was found (adjusted odds ratio [OR] 4.39, 95% CI 3.29-5.86), and despite the increasing prevalence of hypertension (OR 1.54, 95% CI 1.21-1.96) and atrial fibrillation (OR 1.7, 95% CI 1.22-2.36), preventive use of antihypertensive and antiplatelet drugs was declining. A smaller number of participants in certain subgroup-specific analyses (e.g., black ethnicity and LAA subtype) could have limited the power to identify significant trends.ConclusionsThe incidence of ISs has been declining since 2000 in all age groups but to a lesser extent in the black population. The reported changes in medication use are unlikely to fully explain the reduction in stroke incidence; however, innovative prevention strategies and better management of risk factors may contribute further reduction.
| S-EPMC6173399 | biostudies-literature
Project description:BackgroundPredicting risk of disease from genotypes is being increasingly proposed for a variety of diagnostic and prognostic purposes. Genome-wide association studies (GWAS) have identified a large number of genome-wide significant susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC), two subtypes of inflammatory bowel disease (IBD). Recent studies have demonstrated that including only loci that are significantly associated with disease in the prediction model has low predictive power and that power can substantially be improved using a polygenic approach.MethodsWe performed a comprehensive analysis of risk prediction models using large case-control cohorts genotyped for 909,763 GWAS SNPs or 123,437 SNPs on the custom designed Immunochip using four prediction methods (polygenic score, best linear genomic prediction, elastic-net regularization and a Bayesian mixture model). We used the area under the curve (AUC) to assess prediction performance for discovery populations with different sample sizes and number of SNPs within cross-validation.ResultsOn average, the Bayesian mixture approach had the best prediction performance. Using cross-validation we found little differences in prediction performance between GWAS and Immunochip, despite the GWAS array providing a 10 times larger effective genome-wide coverage. The prediction performance using Immunochip is largely due to the power of the initial GWAS for its marker selection and its low cost that enabled larger sample sizes. The predictive ability of the genomic risk score based on Immunochip was replicated in external data, with AUC of 0.75 for CD and 0.70 for UC. CD patients with higher risk scores demonstrated clinical characteristics typically associated with a more severe disease course including ileal location and earlier age at diagnosis.ConclusionsOur analyses demonstrate that the power of genomic risk prediction for IBD is mainly due to strongly associated SNPs with considerable effect sizes. Additional SNPs that are only tagged by high-density GWAS arrays and low or rare-variants over-represented in the high-density region on the Immunochip contribute little to prediction accuracy. Although a quantitative assessment of IBD risk for an individual is not currently possible, we show sufficient power of genomic risk scores to stratify IBD risk among individuals at diagnosis.
| S-EPMC5576242 | biostudies-literature
Project description:Modifiable risk factors like obesity, hypertension, smoking, physical inactivity or atrial fibrillation account for a significant proportion of the risk for ischaemic stroke, but genetic variation is also believed to contribute to the risk, although few genetic risk variants were identified to date. Common clinical subtypes of stroke are caused by cardiac embolism, large artery atherosclerosis and small cerebral vessel disease. Each of these underlying pathologies may have a specific genetic architecture.Previous genome-wide association studies (GWAS) showed association of variants near PITX2 and ZFHX3 with atrial fibrillation and stroke. ANRIL (antisense Non-coding RNA in the INK4 Locus (harboring the CDKN2A/B genes)) variants were related to a variety of vascular diseases (myocardial infarction, aortic and intracranial aneurysm), including ischaemic stroke. Now a recent GWAS published in Nature Genetics confirmed these previous associations, analyzed the specificity of the previous associations with particular stroke subtypes and identified a new association between HDAC9 and large vessel stroke. The findings suggest that well-recognized clinical stroke subtypes correspond to distinct aetiological entities. However, the molecular pathways that are affected by the identified genetic variants are not yet pinpointed, and the observed associations apply only for some, but not all victims of a specific stroke aetiology.
| S-EPMC3403977 | biostudies-other