Dataset Information

Association of Atrial Fibrillation With White Matter Disease.

ABSTRACT: Background and Purpose- Evidence suggests that atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. White matter disease (WMD) is a potential mechanism linking AF to cognitive impairment. In this study, we explored the association between prevalent AF and WMD. Methods- We performed a cross-sectional analysis of participants attending the ARIC-NCS (Atherosclerosis Risk in Communities-Neurocognitive Study) in 2011 to 2013 who underwent brain magnetic resonance imaging. AF was ascertained from study visit electrocardiograms or prior hospitalization codes. Extent of WMD was defined by measures of white matter (WM) microstructural integrity and WM hyperintensity volume. Multivariable linear regression models were used to assess the association between AF and WMD. Results- Among 1899 participants (mean age, 76 years; 28% black; 60% women), 133 (7%) had prevalent AF. After multivariable adjustment, differences between participants with and without AF were -0.001 (95% CI, -0.006 to 0.004) for global WM fractional anisotropy, 0.031×10-4 mm2/s (95% CI, -0.075 to 0.137) for global WM mean diffusivity, and 0.08 mm3 (95% CI, -0.14 to 0.30) for WM hyperintensity volume. Conclusions- The results suggest that there is no association between prevalent AF and WMD.

SUBMITTER: Shao IY

PROVIDER: S-EPMC6433530 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Association of Atrial Fibrillation With White Matter Disease.

Shao Iris Yuefan IY Power Melinda C MC Mosley Thomas T Jack Clifford C Gottesman Rebecca F RF Chen Lin Y LY Norby Faye L FL Soliman Elsayed Z EZ Alonso Alvaro A

Stroke 20190401 4

Background and Purpose- Evidence suggests that atrial fibrillation (AF) is associated with increased risk of cognitive decline and dementia, even in the absence of stroke. White matter disease (WMD) is a potential mechanism linking AF to cognitive impairment. In this study, we explored the association between prevalent AF and WMD. Methods- We performed a cross-sectional analysis of participants attending the ARIC-NCS (Atherosclerosis Risk in Communities-Neurocognitive Study) in 2011 to 2013 who ...[more]

PMID: 30879437

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Project description:BackgroundAtrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis.MethodsThe genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance-weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR.ResultsA higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta -0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E-12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta -0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome.ConclusionsThis study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.

Project description:ImportanceAir pollution is associated with cardiovascular outcomes. Specifically, fine particulate matter measuring 2.5 μm or less (PM2.5) is associated with thrombosis, stroke, and myocardial infarction. Few studies have examined particulate matter and stroke risk in individuals with atrial fibrillation (AF).ObjectiveTo assess the association of residential-level pollution exposure in 1 year and ischemic stroke in individuals with AF.Design, setting, and participantsThis cohort study included 31 414 individuals with AF from a large regional health care system in an area with historically high industrial pollution. All participants had valid residential addresses for geocoding and ascertainment of neighborhood-level income and educational level. Participants were studied from January 1, 2007, through September 30, 2015, with prospective follow-up through December 1, 2017. Data analysis was performed from March 14, 2018, to October 9, 2019.ExposuresExposure to PM2.5 ascertained using geocoding of addresses and fine-scale air pollution exposure surfaces derived from a spatial saturation monitoring campaign and land-use regression modeling. Exposure to PM2.5 was estimated annually across the study period at the residence level.Main outcomes and measuresMultivariable-adjusted stroke risk by quartile of residence-level and annual PM2.5 exposure.ResultsThe cohort included 31 414 individuals (15 813 [50.3%] female; mean [SD] age, 74.4 [13.5] years), with a median follow-up of 3.5 years (interquartile range, 1.6-5.8 years). The mean (SD) annual PM2.5 exposure was 10.6 (0.7) μg/m3. A 1-SD increase in PM2.5 was associated with a greater risk of stroke after both adjustment for demographic and clinical variables (hazard ratio [HR], 1.08; 95% CI, 1.03-1.14) and multivariable adjustment that included neighborhood-level income and educational level (HR, 1.07; 95% CI, 1.00-1.14). The highest quartile of PM2.5 exposure had an increased risk of stroke relative to the first quartile (HR, 1.36; 95% CI, 1.18-1.58). After adjustment for clinical covariates, income, and educational level, risk of stroke remained greater for the highest quartile of exposure relative to the first quartile (HR, 1.21; 95% CI, 1.01-1.45).Conclusions and relevanceThis large cohort study of individuals with AF identified associations between PM2.5 and risk of ischemic stroke. The results suggest an association between fine particulate air pollution and cardiovascular disease and outcomes.

Project description:CONTEXT:Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. OBJECTIVE:To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS:The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 [SD, 13] years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME MEASURES:Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF [onset ?65 years old], number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. RESULTS:Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval [CI], 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 [95% CI, 0.826-0.858]; premature familial AF, C statistic, 0.846 [95% CI, 0.831-0.862]; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of <5%, 5%-10%, and >10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009). CONCLUSIONS:In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.

Project description:Patients with Alzheimer's disease (AD) often have cerebral white matter (WM) hyperintensities on MRI and microinfarcts of presumed microvascular origin pathologically. Here, we determined if vasodilator dysfunction of WM-penetrating arterioles is associated with pathologically defined WM injury and disturbances in quantitative MRI-defined WM integrity in patients with mixed microvascular and AD pathology. We analyzed tissues from 28 serially collected human brains from research donors diagnosed with varying degrees of AD neuropathologic change (ADNC) with or without cerebral microinfarcts (mVBI). WM-penetrating and pial surface arteriolar responses to the endothelium-dependent agonist bradykinin were quantified ex vivo with videomicroscopy. Vascular endothelial nitric oxide synthase (eNOS) and NAD(P)H-oxidase (Nox1, 2 and 4 isoforms) expression were measured with quantitative PCR. Glial fibrillary acidic protein (GFAP)-labeled astrocytes were quantified by unbiased stereological approaches in regions adjacent to the sites of WM-penetrating vessel collection. Post-mortem diffusion tensor imaging (DTI) was used to measure mean apparent diffusion coefficient (ADC) and fractional anisotropy (FA), quantitative indices of WM integrity. In contrast to pial surface arterioles, white matter-penetrating arterioles from donors diagnosed with high ADNC and mVBI exhibited a significantly reduced dilation in response to bradykinin when compared to the other groups. Expression of eNOS was reduced, whereas Nox1 expression was increased in WM arterioles in AD and mVBI cases. WM astrocyte density was increased in AD and mVBI, which correlated with a reduced vasodilation in WM arterioles. Moreover, in cases with low ADNC, bradykinin-induced WM arteriole dilation correlated with lower ADC and higher FA values. Comorbid ADNC and mVBI appear to synergistically interact to selectively impair bradykinin-induced vasodilation in WM-penetrating arterioles, which may be related to reduced nitric oxide- and excess reactive oxygen species-mediated vascular endothelial dysfunction. WM arteriole vasodilator dysfunction is associated with WM injury, as supported by reactive astrogliosis and MRI-defined disrupted WM microstructural integrity.

Dataset Information

Association of Atrial Fibrillation With White Matter Disease.

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Association of Atrial Fibrillation With White Matter Disease.

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