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Race and stroke in an atrial fibrillation inception cohort: Findings from the Penn Atrial Fibrillation Free study.

ABSTRACT: BACKGROUND:Stroke may be the initial manifestation of atrial fibrillation (AF). Limited studies, however, have evaluated racial differences in stroke before the diagnosis of AF. OBJECTIVE:We assessed racial differences in strokes that occurred before and after AF diagnosis in the Penn Atrial Fibrillation Free study. METHODS:The Penn Atrial Fibrillation Free study consists of 56,835 patients from the University of Pennsylvania Health System who were free of AF at the index visit. We developed an inception cohort of 3507 patients with incident AF and without any remote history of stroke. RESULTS:Among the AF inception cohort, there were 538 patients with ischemic strokes and 54 with hemorrhagic strokes. Nearly half (n = 254; 47%) of the ischemic strokes occurred within a 6-month period before the diagnosis of AF. Of these, the majority of strokes occurred either on the day of (n = 158) or within a 7-day period before (n = 30) the diagnosis of incident AF. The remaining 284 (53%) ischemic strokes occurred a median of 3.6 years (interquartile range 1.9-5.4 years) after AF diagnosis. Compared with whites, blacks had an independently higher risk of having an ischemic stroke either before (adjusted odds ratio 1.37; 95% confidence interval 1.03-1.81) or after (adjusted hazard ratio 1.67; 95% confidence interval 1.30-2.14) AF diagnosis. CONCLUSION:In the population with incident AF, nearly half of the ischemic strokes occurred before the diagnosis of AF. Compared with whites, blacks had a higher risk of developing an ischemic stroke that persisted whether the stroke occurred in the period either before or after AF diagnosis.

SUBMITTER: Patel PJ

PROVIDER: S-EPMC5879006 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Race and stroke in an atrial fibrillation inception cohort: Findings from the Penn Atrial Fibrillation Free study.

Patel Parin J PJ Katz Ronit R Borovskiy Yuliya Y Killian Anthony A Levine Joshua M JM McNaughton Nelson W NW Callans David D Supple Gregory G Dixit Sanjay S Epstein Andrew E AE Marchlinski Francis E FE Deo Rajat R

Heart rhythm 20180220 4

<h4>Background</h4>Stroke may be the initial manifestation of atrial fibrillation (AF). Limited studies, however, have evaluated racial differences in stroke before the diagnosis of AF.<h4>Objective</h4>We assessed racial differences in strokes that occurred before and after AF diagnosis in the Penn Atrial Fibrillation Free study.<h4>Methods</h4>The Penn Atrial Fibrillation Free study consists of 56,835 patients from the University of Pennsylvania Health System who were free of AF at the index v ...[more]

PMID: 29475795

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Project description:ObjectiveWe report on: (1) the proportion of patients with known atrial fibrillation (AF); and (2) demographic, clinical or radiological differences between patients with known AF (and not treated) and patients with newly diagnosed AF, in a cohort of patients who presented with ischaemic stroke or transient ischaemic attack (TIA) not previously treated with anticoagulation.DesignWe reviewed cross-sectional baseline demographic and clinical data from a prospective observational cohort study, (CROMIS-2).SettingPatients were recruited from 79 hospital stroke centres throughout the UK and one centre in the Netherlands.ParticipantsPatients were eligible if they were adults who presented with ischaemic stroke or TIA and AF and had not been previously treated with oral anticoagulation.Main outcome measuresProportion of patients with known AF before index ischaemic stroke or TIA from a cohort of patients who have not been previously treated with oral anticoagulation. Secondary analysis includes the comparison of CHA2DS2-VASc and HAS-BLED scores and other demographics and risk factors between those with newly diagnosed AF and those with previously known AF.ResultsOf 1470 patients included in the analysis (mean age 76 years (SD 10)), 622 (42%) were female; 999 (68%) patients had newly diagnosed AF and 471 (32%) patients had known AF. Of the 471 patients with known AF, 68% had a strong indication for anticoagulation and 89% should have been considered for anticoagulation based upon CHA2DS2-VASc score. Patients with known AF were more likely to have a prior history of dementia (4% vs 2%, p=0.02) and had higher HAS-BLED scores (median 3 vs 2). CHA2DS2-VASc, other risk factors and demographics were similar.ConclusionsAbout 1/3 of patients who present with stroke and have AF who have not been treated with oral anticoagulation have previously known AF. Of these patients, at least 68% were not adequately treated with oral anticoagulation.Trial registration numberNCT02513316.

Project description:BackgroundAlthough growing evidence links air pollution to stroke incidence, less is known about the effect of air pollution on atrial fibrillation (AF), an important risk factor for stroke.ObjectivesWe assessed the associations between air pollution and incidence of AF and stroke. We also sought to characterize the shape of pollutant-disease relationships.MethodsThe population-based cohort comprised 5,071,956 Ontario residents, age 35–85 y and without the diagnoses of both outcomes on 1 April 2001 and was followed up until 31 March 2015. AF and stroke cases were ascertained using health administrative databases with validated algorithms. Based on annual residential postal codes, we assigned 5-y running average concentrations of fine particulate matter ([Formula: see text]), nitrogen dioxide ([Formula: see text]), and ozone ([Formula: see text]) from satellite-derived data, a land-use regression model, and a fusion-based method, respectively, as well as redox-weighted averages of [Formula: see text] and [Formula: see text] ([Formula: see text]) for each year. Using Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of AF and stroke with each of these pollutants, adjusting for individual- and neighborhood-level variables. We used newly developed nonlinear risk models to characterize the shape of pollutant–disease relationships.ResultsBetween 2001 and 2015, we identified 313,157 incident cases of AF and 122,545 cases of stroke. Interquartile range increments of [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] were associated with increases in the incidence of AF [HRs (95% CIs): 1.03 (1.01, 1.04), 1.02 (1.01, 1.03), 1.01 (1.00, 1.02), and 1.01 (1.01, 1.02), respectively] and the incidence of stroke [HRs (95% CIs): 1.05 (1.03, 1.07), 1.04 (1.01, 1.06), 1.05 (1.03, 1.06), and 1.05 (1.04, 1.06), respectively]. Associations of similar magnitude were found in various sensitivity analyses. Furthermore, we found a near-linear association for stroke with [Formula: see text], whereas [Formula: see text], [Formula: see text]-, and [Formula: see text] relationships exhibited sublinear shapes.ConclusionsAir pollution was associated with stroke and AF onset, even at very low concentrations. https://doi.org/10.1289/EHP4883.

Project description:ImportanceBlack and Hispanic patients are less likely than white patients to use oral anticoagulants for atrial fibrillation. Little is known about racial/ethnic differences in use of direct-acting oral anticoagulants (DOACs) for atrial fibrillation.ObjectiveTo assess racial/ethnic differences in the use of oral anticoagulants, particularly DOACs, in patients with atrial fibrillation.Design, setting, and participantsThis cohort study used data from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II, a prospective, US-based registry of outpatients with nontransient atrial fibrillation 21 years and older who were followed up from February 2013 to July 2016. Data were analyzed from February 2017 to February 2018.ExposuresSelf-reported race/ethnicity as white, black, or Hispanic.Main outcomes and measuresThe primary outcome was use of any oral anticoagulant, particularly DOACs. Secondary outcomes included the quality of anticoagulation received and oral anticoagulant discontinuation at 1 year.ResultsOf 12 417 patients, 11 100 were white individuals (88.6%), 646 were black individuals (5.2%), and 671 were Hispanic individuals (5.4%) with atrial fibrillation. After adjusting for clinical features, black individuals were less likely to receive any oral anticoagulant than white individuals (adjusted odds ratio [aOR], 0.75 [95% CI, 0.56, 0.99]) and less likely to receive DOACs if an anticoagulant was prescribed (aOR, 0.63 [95% CI, 0.49-0.83]). After further controlling for socioeconomic factors, oral anticoagulant use was no longer significantly different in black individuals (aOR, 0.78 [95% CI, 0.59-1.04]); among patients using oral anticoagulants, DOAC use remained significantly lower in black individuals (aOR, 0.73 [95% CI, 0.55-0.95]). There was no significant difference between white and Hispanic groups in use of oral anticoagulants. Among patients receiving warfarin, the median time in therapeutic range was lower in black individuals (57.1% [IQR, 39.9%-72.5%]) and Hispanic individuals (51.7% [interquartile range {IQR}, 39.1%-66.7%]) than white individuals (67.1% [IQR, 51.8%-80.6%]; P < .001). Black and Hispanic individuals treated with DOACs were more likely to receive inappropriate dosing than white individuals (black patients, 61 of 394 [15.5%]; Hispanic patients, 74 of 409 [18.1%]; white patients, 1003 of 7988 [12.6%]; P = .01). One-year persistence on oral anticoagulants was the same across groups.Conclusions and relevanceAfter controlling for clinical and socioeconomic factors, black individuals were less likely than white individuals to receive DOACs for atrial fibrillation, with no difference between white and Hispanic groups. When atrial fibrillation was treated, the quality of anticoagulant use was lower in black and Hispanic individuals. Identifying modifiable causes of these disparities could improve the quality of care in atrial fibrillation.

Project description:Introduction: Atrial fibrillation (AF) is the most common arrhythmia and affects around 1% of the population with increasing incidence and substantial morbidity. Functional effects of genetic variants associated with AF should help to identify targets involved in AF initiation and/or subsequent remodeling. Gene variants next to the gene of the transcription factor PITX2 (paired-like homeodomain transcription factor 2) showed the strongest association with AF. A significant number of AF patients showed reduced PITX2 levels in the left atrium. Mouse models have been used to study functional aspects of PITX2 gene deletion (“knock out”), but there are substantial differences in atrial electrophysiology between mouse and human . HiPSC-CM should be able to bridge the gap, provided the cells reproduce typical characteristics of human atrium. Methods: PITX2 knock out samples from a control cell line of human induced pluripotent stem cells (hiPSC) were obtained. Differentiation and generation of Atrial-like engineered heart tissue (aEHT) was performed. RNA-sequencing (RNA-Seq), Quantitative Real-time PCR (RT-qPCR), Protein analysis by Western Blot, Contraction and force analysis, action potential measurements, Calcium current measurements and differential gene expression analysis were run on the samples. Results: Effective knock out of PITX2 was confirmed by mRNA sequencing and WB. It was shown that PITX2 deficiency reduces contraction force. PITX2 deficiency induces action potential triangulation with more negative maximum diastolic potential. Activation of muscarinic receptors shortens APD in both PITX2 knockout and controls but hyperpolarization is lost in PITX2 knock out. It was shown that Ca2+ current density is smaller in PITX2 knock out than controls. We found that more negative MDP in PITX2 knock out is not associated with higher IK1. Conclusion: We improved atrial differentiation, coming very close to human atrial electrophysiology. We demonstrate that PITX2 deficiency induces key characteristics known from persistent AF.

Dataset Information

Race and stroke in an atrial fibrillation inception cohort: Findings from the Penn Atrial Fibrillation Free study.

Publications

Race and stroke in an atrial fibrillation inception cohort: Findings from the Penn Atrial Fibrillation Free study.

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