Dataset Information

The ?-fibrinogen gene 455G/A polymorphism associated with cardioembolic stroke in atrial fibrillation with low CHA2DS2-VaSc score.

ABSTRACT: Previous work has suggested that ischemic stroke (IS) may be more likely to occur in individuals with a genetic predisposition. In this study, we investigated the potential association of IS-relevant genetic risk factors with cardioembolic stroke (CES) in atrial fibrillation (AF) patients with low CHA2DS2-VaSc score. Genotyping was performed using the GenomeLab SNPstream genotyping platform for five IS-relevant SNPs (MMP-9 C1562T, ALOX5AP SG13S114A/T, MTHFR 677?C/T, FGB 455?G/A, and eNOS G298A) in 479 AF patients with CES and 580 age and sex-matched AF patients without CES. The multivariate analysis adjusted for potential confounders and demonstrated that FGB 455?G/A was independently associated with increased risk of CES in AF patients and the significance remained after Bonferroni correction in the additive, dominant, and recessive models with ORs of 1.548 (95% CI: 1.251-1.915, P?=?0.001), 1.588 (95% CI: (1.226-2.057, P?=?0.003), and 2.394 (95% CI: 1.357-4.223, P?=?0.015), respectively. Plasma fibrinogen levels were significantly higher in patients with the A allele compared with patients with genotype of GG (3.29?±?0.38?mg/dl vs. 2.87?±?0.18?mg/dl, P?

SUBMITTER: Hu X

PROVIDER: S-EPMC5727505 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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The β-fibrinogen gene 455G/A polymorphism associated with cardioembolic stroke in atrial fibrillation with low CHA<sub>2</sub>DS<sub>2</sub>-VaSc score.

Hu Xiaofeng X Wang Junjun J Li Yaguo Y Wu Jiong J Qiao Song S Xu Shanhu S Huang Jun J Chen Linhui L

Scientific reports 20171213 1

Previous work has suggested that ischemic stroke (IS) may be more likely to occur in individuals with a genetic predisposition. In this study, we investigated the potential association of IS-relevant genetic risk factors with cardioembolic stroke (CES) in atrial fibrillation (AF) patients with low CHA2DS2-VaSc score. Genotyping was performed using the GenomeLab SNPstream genotyping platform for five IS-relevant SNPs (MMP-9 C1562T, ALOX5AP SG13S114A/T, MTHFR 677 C/T, FGB 455 G/A, and eNOS G298A) ...[more]

PMID: 29235504

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Project description:BACKGROUND:In people with atrial fibrillation (AF), periods of sinus rhythm present an opportunity to detect prothrombotic atrial remodeling through measurement of P-wave indices (PWIs)-prolonged P-wave duration, abnormal P-wave axis, advanced interatrial block, and abnormal P-wave terminal force in lead V1. We hypothesized that the addition of PWIs to the CHA2DS2-VASc score would improve its ability to predict AF-related ischemic stroke. METHODS:We included 2229 participants from the ARIC study (Atherosclerosis Risk in Communities) and 700 participants from MESA (Multi-Ethnic Study of Atherosclerosis) with incident AF who were not on anticoagulants within 1 year of AF diagnosis. PWIs were obtained from study visit ECGs before development of AF. AF was ascertained using study visit ECGs and hospital records. Ischemic stroke cases were based on physician adjudication of hospital records. We used Cox proportional hazards models to estimate hazard ratios and 95% CIs of PWIs for ischemic stroke. Improvement in 1-year stroke prediction was assessed by C-statistic, categorical net reclassification improvement, and relative integrated discrimination improvement. RESULTS:Abnormal P-wave axis was the only PWI associated with increased ischemic stroke risk (hazard ratio, 1.84; 95% CI, 1.33-2.55) independent of CHA2DS2-VASc variables, and that resulted in meaningful improvement in stroke prediction. The ? estimate was approximately twice that of the CHA2DS2-VASc variables, and thus abnormal P-wave axis was assigned 2 points to create the P2-CHA2DS2-VASc score. This improved the C-statistic (95% CI) from 0.60 (0.51-0.69) to 0.67 (0.60-0.75) in ARIC and 0.68 (0.52-0.84) to 0.75 (0.60-0.91) in MESA (validation cohort). In ARIC and MESA, the categorical net reclassification improvements (95% CI) were 0.25 (0.13-0.39) and 0.51 (0.18-0.86), respectively, and the relative integrated discrimination improvement (95% CI) were 1.19 (0.96-1.44) and 0.82 (0.36-1.39), respectively. CONCLUSIONS:Abnormal P-wave axis-an ECG correlate of left atrial abnormality- improves ischemic stroke prediction in AF. Compared with CHA2DS2-VASc, the P2-CHA2DS2-VASc is a better prediction tool for AF-related ischemic stroke.

Project description:Background and Purpose- Despite modest predictive ability for ischemic stroke (IS), the CHA2DS2-VASc score is widely used for stroke prediction in atrial fibrillation. Among patients with atrial fibrillation, we aimed to (1) compare the IS or transient ischemic attack (TIA) incidence by CHA2DS2-VASc in blacks and Hispanics versus whites; (2) compare predictive ability of CHA2DS2-VASc score for IS or TIA in blacks and Hispanics versus whites; and (3) determine improvement in predictive ability of CHA2DS2-VASc score from addition of race/ethnicity. Methods- Using data from Optum Clinformatics, a large administrative claims database, we analyzed patients with atrial fibrillation enrolled in commercial and Medicare Advantage health plans from 2009 to 2015. We computed IS or TIA incidence rates, improvement in C statistic, continuous and categorical net reclassification improvement, and relative integrated discrimination improvement from addition of race/ethnicity to CHA2DS2-VASc. Results- A total of 267 419 patients (mean age, 73.1 [SD, 12.3] years; 46.6% women; 84.2% white, 8.5% black, 7.3% Hispanic) were studied. After a mean follow-up of 22 months, there were 6202 IS or TIA events. IS or TIA incidence rates were higher in blacks than Hispanics or whites (1.65, 1.40, and 1.22 cases per 100 person-years, respectively) and increased with higher CHA2DS2-VASc, with no race/ethnicity-based differences ( P for interaction=0.17). The CHA2DS2-VASc and CHA2DS2-VASc+race/ethnicity C statistic (95% CI) were 0.679 (0.670-0.686) and 0.679 (0.671-0.688). The CHA2DS2-VASc C statistic in the 3 groups were comparable. With addition of race/ethnicity, the categorical net reclassification improvement, continuous net reclassification improvement, and relative integrated discrimination improvement were -0.045 (95% CI, -0.067 to -0.025), 0.045 (95% CI, 0.025-0.068), and 0.016 (95% CI, 0.014-0.018). Conclusions- The predictive ability of CHA2DS2-VASc for IS or TIA in atrial fibrillation is comparable among whites, blacks, and Hispanics; hence, it can be used in the latter 2 groups. Addition of race/ethnicity to the CHA2DS2-VASc does not improve its predictive ability.

Project description:ImportanceCurrent guidelines support treating atrial fibrillation (AF) and atrial flutter (AFL) as equivalent risk factors for ischemic stroke stratified by CHA2DS2-VASc scores, recommending anticoagulation therapy for patients with a CHA2DS2-VASc score of 2 or higher, but some studies found differences in clinical outcomes.ObjectiveTo investigate differences in clinical outcomes among AF, AFL, and matched control cohorts.Design, setting, and participantsThis nationwide cohort study analyzed data from the Taiwan National Health Insurance Research Database from January 1, 2001, through December 31, 2012. Follow-up and data analysis ended December 31, 2012. A total of 219 416 age- and sex-matched individuals participated in the study. Clinical outcomes were compared after stratification by CHA2DS2-VASc score (possible score range, 0-9; higher scores indicate greater risk of ischemic stroke).Main outcomes and measuresIschemic stroke, heart failure hospitalization, and all-cause mortality among the AF, AFL, and matched control cohorts were analyzed using Cox proportional hazards regression.ResultsThis study comprised 188?811 patients in the AF cohort (mean [SD] age, 73.8 [13.4] years; 104 703 [55.5%] male), 6121 patients in the AFL cohort (mean [SD] age, 67.7 [15.8] years; 3735 [61.0%] male), and 24?484 patients in the matched control cohort (mean [SD] age, 67.3 [15.6] years; 14 940 [61.0%] male). The patients with AF were older, were more predominantly female, and had higher CHA2DS2-VASc scores than the patients with AFL and the control participants. After stratification by CHA2DS2-VASc score, the incidence densities (IDs; events per 100 person-years) of ischemic stroke (AF cohort: ID, 3.08; 95% CI, 3.03-3.13; AFL cohort: ID, 1.45; 95% CI, 1.28-1.62; controls: ID, 0.97; 95% CI, 0.92-1.03), heart failure hospitalization (AF cohort: ID, 3.39; 95% CI, 3.34-3.44; AFL cohort: ID, 1.57; 95% CI, 1.39-1.74; controls: ID, 0.32; 95% CI, 0.29-0.35), and all-cause mortality (AF cohort: ID, 17.8; 95% CI, 17.7-17.9; AFL cohort: ID, 13.9; 95% CI, 13.4-14.4; controls: ID, 4.2; 95% CI, 4.1-4.4) were significantly higher in the AF cohort than in the matched control cohort. For the AFL cohort vs the matched control cohort, the incidences of heart failure hospitalization and all-cause mortality were significantly higher across all levels, but the incidence of ischemic stroke was only significantly higher at CHA2DS2-VASc scores of 5 to 9. For the AF cohort vs the AFL cohort, the incidences of ischemic stroke and heart failure hospitalization were significantly higher at a CHA2DS2-VASc score of 1 or higher, but the incidence of all-cause mortality was significantly higher only at CHA2DS2-VASc scores of 1 to 3.Conclusions and relevanceThis study found different clinical outcomes between patients with AFL and AF and those without AF and AFL. The current recommended level of the CHA2DS2-VASc score in preventing ischemic stroke in patients with AFL should be reevaluated.

Project description:AimsThe GRACE and CHA2DS2-VASc risk score are developed for risk stratification in patients with acute coronary syndrome and AF, respectively. We aimed to assess the predictive performance of the GRACE score and CHA2DS2-VASc score among patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).MethodsConsecutive patients with a diagnosis of AF admitted to our hospital for PCI between January 2016 and December 2018 were included and followed up for at least 1 year. The primary endpoint was a composite of major adverse cardiac events (MACEs) including all-cause mortality, repeat revascularization, myocardial infarction, or ischaemic stroke.ResultsA total of 1452 patients were identified. Cox regression demonstrated that the GRACE (HR 1.014, 95% CI 1.008-1.020, p < 0.001) but not the CHA2DS2-VASc score was associated with the risk of MACEs. Both GRACE and CHA2DS2-VASc scores were predictive of all-cause mortality with HR of 1.028 (95% CI 1.020-1.037, p < 0.001) and 1.334 (95% CI 1.107-1.632, p = 0.003). Receiver operating characteristic analyses showed both scores had similar discrimination capacity for all-cause mortality (C-statistic: 0.708 for GRACE vs. 0.661 for CHA2DS2-VASc, p = 0.299). High GRACE score was also significantly associated with increased risk of ischaemic stroke (HR 1.018, 95% CI 1.005-1.031, p = 0.006) and major bleeding (HR 1.012, 95% CI 1.001-1.024, p = 0.039), whereas high CHA2DS2-VASc score was not.ConclusionsHigh GRACE score but not CHA2DS2-VASc score were both associated with an increased risk of MACEs after PCI in patients with AF. The GRACE and CHA2DS2-VASc scores have similar predictive performance for predicting all-cause mortality.Key messages:In patients with AF undergoing PCI, increasing GRACE but not CHA2DS2-VASc scores was independently associated high risk of MACEs.The GRACE score could also help identify patients at higher risk of stroke and major bleeding.Both GRACE and CHA2DS2-VASc scores showed good ability in the prediction of all-cause mortality.

Dataset Information

The ?-fibrinogen gene 455G/A polymorphism associated with cardioembolic stroke in atrial fibrillation with low CHA2DS2-VaSc score.

Publications

The β-fibrinogen gene 455G/A polymorphism associated with cardioembolic stroke in atrial fibrillation with low CHA<sub>2</sub>DS<sub>2</sub>-VaSc score.

Similar Datasets

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