Genetic heterogeneity of atrial fibrillation susceptibility loci across racial or ethnic groups.
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ABSTRACT:
SUBMITTER: Huang H
PROVIDER: S-EPMC5837825 | biostudies-literature | 2017 Sep
REPOSITORIES: biostudies-literature
Publications
Genetic heterogeneity of atrial fibrillation susceptibility loci across racial or ethnic groups.
European heart journal 20170901 34
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Project description:ImportanceThere is a genetic predisposition to early-onset atrial fibrillation (EOAF) in European American individuals. However, the role of family history in the pathogenesis of EOAF in racial and ethnic minorities remains unclear.ObjectiveTo determine whether probands with EOAF across racial and ethnic groups have a higher rate of AF in first-degree family members than racially and ethnically matched control patients with non-early-onset AF (non-EOAF).Design, setting, and participantsIn this cohort study, patients prospectively enrolled in a clinical and genetic biorepository were administered baseline questionnaires that included questions about family history of AF. Early-onset AF was defined as AF occurring in probands aged 60 years or younger in the absence of structural heart disease. All other forms were categorized as non-EOAF. Recruitment took place from July 2015 to December 2017. Analysis was performed in January 2018.Main outcomes and measuresPrimary analysis of reported family history of AF in first-degree relatives with sensitivity analysis restricted to those in whom a family history was confirmed by medical record review and electrocardiogram.ResultsOf 664 patients enrolled (mean [SD] age, 62 [12] years; 407 [61%] male), 267 (40%) were European American; 258 (39%), African American; and 139 (21%), Hispanic/Latino. There was a family history of AF in 36 probands with EOAF (49%) compared with 128 patients with non-EOAF (22%) (difference, 27%; 95% CI, 14%-40%; P < .001). On multivariable analysis, the adjusted odds of a proband with EOAF who was of African descent (odds ratio [OR], 2.69; 95% CI, 1.06-6.91; P < .001) or Hispanic descent (OR, 9.25; 95% CI, 2.37-36.23; P = .002) having a first-degree relative with AF were greater than those of European descent (OR, 2.51; 95% CI, 1.29-4.87; P = .006). Overall, probands with EOAF were more likely to have a first-degree relative with AF compared with patients with non-EOAF (adjusted OR, 3.02; 95% CI, 1.82-4.95; P < .001) across the 3 racial and ethnic groups. Atrial fibrillation in a first-degree family member was confirmed in 32% of probands with EOAF vs 11% of those with non-EOAF (difference, 21%; 95% CI, 11%-33%; P < .001). Furthermore, African American (28% vs 5%; difference, 23%; 95% CI, 4%-43%; P = .001), European American (35% vs 20%; difference, 15%; 95% CI, 1%-30%; P = .03), and Hispanic/Latino (30% vs 5%; difference, 25%; 95% CI, 4%-54%; P = .02) probands with EOAF were more likely to have a first-degree relative with confirmed AF vs racially and ethnically matched control patients with non-EOAF. The positive and negative predictive values for a family history of confirmed AF were both 89%.Conclusions and relevanceProbands of African or Hispanic/Latino descent with EOAF were more likely to have a first-degree relative with AF when compared with European American individuals. These findings support genetic predisposition to EOAF across all 3 races.
| S-EPMC6324458 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common clinical arrhythmia, and it results in adverse outcomes and increased healthcare costs. Racial and ethnic differences in AF management, although recognized, are poorly understood. This review summarizes racial differences in AF epidemiology, genetics, clinical presentation, and management. In addition, it highlights the underrepresentation of racial and ethnic populations in AF clinical trials, especially trials focused on stroke prevention. Specific strategies are proposed for future research and initiatives that have potential to eliminate racial and ethnic differences in the care of patients with AF. Addressing racial and ethnic disparities in healthcare access, enrollment in clinical trials, resource allocation, prevention, and management will likely narrow the gaps in the care and outcomes of racial and ethnic minorities suffering from AF.
| S-EPMC8712595 | biostudies-literature
Project description:BackgroundAblation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.MethodsTen centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.ResultsFour thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13).ConclusionsHigher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.
| S-EPMC7080569 | biostudies-literature
Project description:BackgroundRhythm control strategies for atrial fibrillation (AF), including catheter ablation, are substantially underused in racial/ethnic minorities in North America.ObjectivesThis study sought to describe outcomes in the CABANA trial as a function of race/ethnicity.MethodsCABANA randomized 2,204 symptomatic participants with AF to ablation or drug therapy including rate and/or rhythm control drugs. Only participants in North America were included in the present analysis, and participants were subgrouped as racial/ethnic minority or nonminority with the use of National Institutes of Health definitions. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.ResultsOf 1,280 participants enrolled in CABANA in North America, 127 (9.9%) were racial and ethnic minorities. Compared with nonminorities, racial and ethnic minorities were younger with median age 65.6 versus 68.5 years, respectively, and had more symptomatic heart failure (37.0% vs 22.0%), hypertension (92.1% vs 76.8%, respectively), and ejection fraction <40% (20.8% vs 7.1%). Racial/ethnic minorities treated with ablation had a 68% relative reduction in the primary endpoint (adjusted hazard ratio [aHR]: 0.32; 95% confidence interval [CI]: 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR: 0.28; 95% CI: 0.10-0.79). Primary event rates in racial/ethnic minority and nonminority participants were similar in the ablation arm (4-year Kaplan-Meier event rates 12.3% vs 9.9%); however, racial and ethnic minorities randomized to drug therapy had a much higher event rate than nonminority participants (27.4% vs. 9.4%).ConclusionAmong racial or ethnic minorities enrolled in the North American CABANA cohort, catheter ablation significantly improved major clinical outcomes compared with drug therapy. These benefits, which were not seen in nonminority participants, appear to be due to worse outcomes with drug therapy. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508).
| S-EPMC8354144 | biostudies-literature
Project description:ImportanceIn patients with paroxysmal atrial fibrillation (AF), rhythm control with either antiarrhythmic drugs (AADs) or catheter ablation has been associated with decreased symptoms, prevention of adverse remodeling, and improved cardiovascular outcomes. Adoption of advanced cardiovascular therapeutics, however, is often slower among patients from racial/ethnic minority groups and those with lower income.ObjectiveTo ascertain the cumulative rates of AAD and catheter ablation use for the management of paroxysmal AF and to investigate for the presence of inequities in AF management by evaluating the association of race/ethnicity and socioeconomic status with their use in the United States.Design, setting, and participantsThis cohort study obtained inpatient, outpatient, and pharmacy claims data from the Optum Clinformatics Data Mart between October 1, 2015, and June 30, 2019. Adult patients (aged ≥18 years) in the database with a diagnosis of incident paroxysmal AF were identified. Patients were excluded if they did not have continuous insurance enrollment for at least 1 year before and at least 6 months after study entry.ExposuresRace/ethnicity and zip code-linked median household income.Main outcomes and measuresTreatment with a rhythm control strategy, and catheter ablation specifically, among those who received rhythm control. Multivariable logistic regression models were used to assess the association of race/ethnicity and zip code-linked median household income with a rhythm control strategy (AADs or catheter ablation) vs a rate control strategy as well as with catheter ablation vs AADs among those receiving rhythm control.ResultsOf the 109 221 patients who met the inclusion criteria, 55 185 were men (50.5%) and 73 523 were White (67.3%), with a median (interquartile range) age of 75 (68-82) years. A total of 86 359 patients (79.1%) were treated with rate control, 19 362 patients (17.7%) with AADs, and 3500 (3.2%) with catheter ablation. Between 2016 and 2019, the cumulative percentage of patients treated with catheter ablation increased from 1.6% to 3.8%. In multivariable analyses, Black race (adjusted odds ratio [aOR], 0.89; 95% CI, 0.83-0.94; P < .001) and lower zip code-linked median household income (aOR for <$50 000: 0.83 [95% CI, 0.79-0.87; P < .001]; aOR for $50 000-$99 999: 0.92 [95% CI, 0.88-0.96; P = <.001] compared with ≥$100 000) were independently associated with lower use of rhythm control. Latinx ethnicity (aOR, 0.73; 95% CI, 0.60-0.89; P = .002) and lower zip code-linked median household income (aOR for <$50 000: 0.61 [95% CI, 0.54-0.69; P < .001]; aOR for $50 000-$99 999: 0.81 [95% CI, 0.72-0.90; P < .001] compared with ≥$100 000) were independently associated with lower catheter ablation use among those receiving rhythm control.Conclusions and relevanceThis study found that despite increased use of rhythm control strategies for treatment of paroxysmal AF, catheter ablation use remained low and patients from racial/ethnic minority groups and those with lower income were less likely to receive rhythm control treatment, especially catheter ablation. These findings highlight inequities in paroxysmal AF management based on race/ethnicity and socioeconomic status.
| S-EPMC7910819 | biostudies-literature
Project description:BackgroundEighteen known susceptibility loci for IgAN account for only a small proportion of IgAN risk.MethodsGenome-wide meta-analysis was performed in 2628 patients and 11,563 controls of Chinese ancestry, and a replication analysis was conducted in 6879 patients and 9019 controls of Chinese descent and 1039 patients and 1289 controls of European ancestry. The data were used to assess the association of susceptibility loci with clinical phenotypes for IgAN, and to investigate genetic heterogeneity of IgAN susceptibility between the two populations. Imputation-based analysis of the MHC/HLA region extended the scrutiny.ResultsIdentification of three novel loci (rs6427389 on 1q23.1 [P=8.18×10-9, OR=1.132], rs6942325 on 6p25.3 [P=1.62×10-11, OR=1.165], and rs2240335 on 1p36.13 [P=5.10×10-9, OR=1.114]), implicates FCRL3, DUSP22.IRF4, and PADI4 as susceptibility genes for IgAN. Rs2240335 is associated with the expression level of PADI4, and rs6427389 is in high linkage disequilibrium with rs11264799, which showed a strong expression quantitative trail loci effect on FCRL3. Of the 24 confirmed risk SNPs, six showed significant heterogeneity of genetic effects and DEFA showed clear evidence of allelic heterogeneity between the populations. Imputation-based analysis of the MHC region revealed significant associations at three HLA polymorphisms (HLA allele DPB1*02, AA_DRB1_140_32657458_T, and AA_DQA1_34_32717152) and two SNPs (rs9275464 and rs2295119).ConclusionsA meta-analysis of GWAS data revealed three novel genetic risk loci for IgAN, and three HLA polymorphisms and two SNPs within the MHC region, and demonstrated the genetic heterogeneity of seven loci out of 24 confirmed risk SNPs. These variants may explain susceptibility differences between Chinese and European populations.
| S-EPMC7790208 | biostudies-literature
Project description:Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules.
| S-EPMC3366038 | biostudies-literature
Project description:Background Catheter ablation is recommended for the treatment of symptomatic atrial fibrillation (AF) refractory to medical therapy. Objective The study sought to examine racial/ethnic and sex differences in complications and AF/atrial flutter (AFL)–related acute healthcare utilization following catheter ablation for AF. Methods We performed a retrospective analysis using data from the Centers for Medicare and Medicaid Services Medicare Standard Analytical Files (October 1, 2014, to September 30, 2019) among patients ≥65 years of age with AF who underwent catheter ablation for rhythm control. The risk of any complication within 30 days and AF/AFL-related acute healthcare utilization within 1 year of ablation by race, ethnicity, and sex were assessed using multivariable Cox regression modeling. Results We identified 95,394 patients for analysis of postablation complications and 68,408 patients for analysis of AF/AFL-related acute healthcare utilization. Both cohorts were ∼95% White and 52% male. Female patients had a slightly elevated risk of complications compared with male patients (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [CI] 1.03–1.12). Black (aHR 0.78, 95% CI 0.77–1.00) and Asian (aHR 0.67, 95% CI 0.50–0.89) patients had lower utilization compared with White patients. Specifically, Asian men (aHR 0.58, 95% CI 0.38–0.91) had lower utilization compared with White men. Conclusion Differences in safety and healthcare utilization after catheter ablation for AF were observed by race/ethnicity and sex groups. Underrepresented racial and ethnic groups with AF had a lower risk of AF/AFL-related acute healthcare utilization postablation.
| S-EPMC10264254 | biostudies-literature
Project description:BackgroundRepresentation trends of women, older adults, and ethnic/racial minorities in randomized controlled trials (RCTs) of atrial fibrillation (AF) are uncertain.MethodsWe systematically reviewed 134 AF related RCTs (phase II and III) encompassing 149,162 participants using Medline and ClinicalTrials.gov through April 2019 to determine representation trends of women, older patients (≥75 years), and ethnic/racial minorities. Weighted data on the prevalence of AF from epidemiological studies were used to compare the representation of the studied groups of interest in AF RCTs to their expected burden of the disease.ResultsOnly 18.7% of the RCTs reported proportion of older patients, and 12.7% RCTs reported ethnic/racial minorities. The proportions of women in RCTs versus general population were 35.2% and 35.1%, of Hispanics were 11.9% and 5.2%, of Blacks were 1.2% and 5.7%, of American Indian/Alaskans were 0.2% and 0.2%, of Asians were 14.2% and 2.4%, of native Hawaiian/Pacific Islanders were 0.05% and 0.1% and of non-Whites were 19.5% and 22.5%, respectively. The weighted mean age (SD) across the trials was 65.3 (3.2) years which was less than the corresponding weighted mean age of 71.1 (4.5) years in the comparative epidemiological data.ConclusionThe reporting of older patients and ethnic/racial minorities was poor in RCTs of AF. The representation of women and American Indian/Alaskan natives matched their expected population share of disease burden. Hispanics and Asians were over-represented and Blacks, native Hawaiian/Pacific Islanders and non-Whites were under-represented in RCTs of AF.
| S-EPMC8404149 | biostudies-literature
Project description:ImportanceRacial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with these disparities is unclear.ObjectiveTo determine whether medical center racial and ethnic composition is associated with overall anticoagulation and disparities in anticoagulation for AF.Design, setting, and participantsRetrospective cohort study of Black, White, and Hispanic patients with incident AF from 2018 to 2021 at 140 Veterans Health Administration medical centers (VAMCs). Data were analyzed from March to November 2023.ExposureVAMC racial and ethnic composition, defined as the proportion of patients from minoritized racial and ethnic groups treated at a VAMC, categorized into quartiles. VAMCs in quartile 1 (Q1) had the lowest percentage of patients from minoritized groups (ie, the reference group).Main outcomes and measuresThe odds of initiating any anticoagulant, direct-acting oral anticoagulant (DOAC), or warfarin therapy within 90 days of an index AF diagnosis, adjusting for sociodemographics, medical comorbidities, and facility factors.ResultsThe cohort comprised 89 791 patients with a mean (SD) age of 73.0 (10.1) years; 87 647 (97.6%) were male, 9063 (10.1%) were Black, 3355 (3.7%) were Hispanic, and 77 373 (86.2%) were White. Overall, 64 770 individuals (72.1%) initiated any anticoagulant, 60 362 (67.2%) initiated DOAC therapy, and 4408 (4.9%) initiated warfarin. Compared with White patients, Black and Hispanic patients had lower rates of any anticoagulant and DOAC therapy initiation but higher rates of warfarin initiation across all quartiles of VAMC racial and ethnic composition. Any anticoagulant therapy initiation was lower in Q4 than Q1 (69.8% vs 74.9%; adjusted odds ratio [aOR], 0.80; 95% CI, 0.69-0.92; P < .001). DOAC and warfarin initiation were also lower in Q4 than in Q1 (DOAC, 69.4% vs 65.3%; aOR, 0.85; 95% CI, 0.74-0.97; P < .001; warfarin, 5.4% vs 4.5%; aOR, 0.82; 95% CI, 0.67-1.00; P < .001). In adjusted models, patients in Q4 were significantly less likely to initiate any anticoagulant therapy than those in Q1 (aOR, 0.88; 95% CI, 0.78-0.99). Patients in Q3 (aOR, 0.75; 95% CI, 0.60-0.93) and Q4 (aOR, 0.69; 95% CI, 0.55-0.87) were significantly less likely to initiate warfarin therapy than those in Q1. There was no significant difference in the adjusted odds of initiating DOAC therapy across racial and ethnic composition quartiles. Although significant Black-White and Hispanic-White differences in initiation of any anticoagulant, DOAC, and warfarin therapy were observed, interactions between patient race and ethnicity and VAMC racial composition were not significant.Conclusions and relevanceIn a national cohort of VA patients with AF, initiation of any anticoagulant and warfarin, but not DOAC therapy, was lower in VAMCs serving more minoritized patients.
| S-EPMC11197447 | biostudies-literature