Dataset Information

Association between familial atrial fibrillation and risk of new-onset atrial fibrillation.

ABSTRACT: 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.

SUBMITTER: Lubitz SA

PROVIDER: S-EPMC3073054 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Association between familial atrial fibrillation and risk of new-onset atrial fibrillation.

Lubitz Steven A SA Yin Xiaoyan X Fontes João D JD Magnani Jared W JW Rienstra Michiel M Pai Manju M Villalon Mark L ML Vasan Ramachandran S RS Pencina Michael J MJ Levy Daniel D Larson Martin G MG Ellinor Patrick T PT Benjamin Emelia J EJ

JAMA 20101113 20

<h4>Context</h4>Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown.<h4>Objective</h4>To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors.<h4>Design, setting, and participants</h4>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 fre ...[more]

PMID: 21076174

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Project description:ImportanceAtrial fibrillation (AF) is the most common cardiac arrhythmia worldwide, with different epidemiological and pathophysiological processes for women vs men and a poorer prognosis for women. Further investigation of sex-specific risk factors associated with AF development in women is warranted.ObjectiveTo investigate the linear and potential nonlinear associations between sex-specific risk factors and the risk of new-onset AF in women.Design, setting, and participantsThis population-based cohort study obtained data from the 2006 to 2010 UK Biobank study, a cohort of more than 500 000 participants aged 40 to 69 years. Participants were women without AF and history of hysterectomy and/or bilateral oophorectomy at baseline. Median follow-up period for AF onset was 11.6 years, and follow-up ended on October 3, 2020.ExposuresSelf-reported, sex-specific risk factors, including age at menarche, history of irregular menstrual cycle, menopause status, age at menopause, years after menopause, age at first live birth, years after last birth, history of spontaneous miscarriages, history of stillbirths, number of live births, and total reproductive years.Main outcomes and measuresThe primary outcome was new-onset AF, which was defined by the use of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code I48.ResultsA total of 235 191 women (mean [SD] age, 55.7 [8.1] years) were included in the present study. During follow-up, 4629 (2.0%) women experienced new-onset AF. In multivariable-adjusted models, history of irregular menstrual cycle was associated with higher AF risk (hazard ratio [HR], 1.34; 95% CI, 1.01-1.79). Both early menarche (age 7-11 years; HR, 1.10 [95% CI, 1.00-1.21]) and late menarche (age 13-18 years; HR, 1.08 [95% CI, 1.00-1.17]) were associated with AF incidence. Early menopause (age 35-44 years; HR, 1.24 [95% CI, 1.10-1.39]) and delayed menopause (age ≥60 years; HR, 1.34 [95% CI, 1.10-1.78]) were associated with higher risk of AF. Compared with women with 1 to 2 live births, those with 0 live births (HR, 1.13; 95% CI, 1.04-1.24) or 7 or more live births (HR, 1.67; 95% CI, 1.03-2.70) both had significantly higher AF risk.Conclusions and relevanceResults of this study suggest that irregular menstrual cycles, nulliparity, and multiparity were associated with higher risk of new-onset AF among women. The results highlight the importance of taking into account the reproductive history of women in devising screening strategies for AF prevention.

Project description:BackgroundFrailty was found to be common in patients with atrial fibrillation/flutter (AF), but there was still a lack of evidence regarding the relationship between frailty and new-onset AF.MethodsWe performed a post hoc analysis of data from the Systolic Blood Pressure Intervention Trial (SPRINT). In addition, we evaluated the relationship between baseline frailty status and new-onset AF in older adult patients with hypertension.ResultsIn total, 7,316 participants were included in our analysis, and a total of 115 new-onset AF occurred during an average of 3.54 years of follow-up. Using SPRINT frailty index criteria, 1,535 fit, 4,041 less fit, and 1,740 frailty were enrolled. Compared with other groups, the incidence of new-onset AF in the frailty group was significantly higher. We constructed three Cox models to assess the relationship between the frailty status (fit group as reference) and new-onset AF. Participants with frailty had a significantly higher risk of new-onset AF compared with the fit group in all the models we used. We combined the fit group and the less fit group into a no frailty group to assess the impact of frailty on new-onset AF in various subgroups. After full adjustment (Model 3), frailty remained associated with the increased risk of new-onset AF compared with the no frailty group [hazard ratio [HR] = 2.09, 95% CI:(1.41, 3.09), p < 0.001]. Additionally, we examined the frailty index as continuous variable to assess the relationship between the frailty index and new-onset AF. The smooth curve showed that log HR appeared to increase linearly. And there was a significant interaction between baseline systolic blood pressure (SBP) categories and frailty on the risk of new-onset AF (p for interaction = 0.030).ConclusionThis study found baseline frailty status was a strong independent risk factor for new-onset AF among older adult patients with hypertension. Screening for frailty should be considered in older adult patients with hypertension to prevent new-onset AF.

Project description:IMPORTANCE:A substantial proportion of patients with atrial fibrillation (AF) die of noncardiovascular causes, and recent studies suggest a link between AF and cancer. OBJECTIVE:To evaluate the associations between AF and cancer in a large, long-term prospective cohort study. DESIGN, SETTING, AND PARTICIPANTS:In this cohort study, a total of 34 691 women 45 years or older and free of AF, cardiovascular disease, and cancer at baseline were prospectively followed up between 1993 and 2013, for incident AF and malignant cancer within the Women's Health Study, a randomized clinical trial of aspirin and vitamin E for the prevention of cardiovascular disease and cancer. Cox proportional hazards models using time-updated covariates were constructed to assess the association of new-onset AF with subsequent cancer and to adjust for potential confounders. Data analysis was performed from December 2014 to May 2015. EXPOSURE:New-onset AF. MAIN OUTCOMES AND MEASURES:Incident malignant cancer confirmed by an end point committee. RESULTS:During a median follow-up of 19.1 years of 34 691 study participants (interquartile range [IQR], 17.6-19.7 years), new-onset AF and malignant cancer were confirmed among 1467 (4.2%) and 5130 (14.8%) participants, respectively. Median age at baseline among participants with new-onset AF and new-onset cancer during follow-up was 58 years (IQR, 52-64 years) and 55 years (IQR, 50-61 years), respectively. Atrial fibrillation was a significant risk factor for incident cancer in age-adjusted (hazard ratio [HR], 1.58; 95% CI, 1.34-1.87; P?<?.001) and multivariable-adjusted (HR, 1.48; 95% CI, 1.25-1.75; P?<?.001) models. The relative risk of cancer was highest in the first 3 months after new-onset AF (HR, 3.54; 95% CI, 2.05-6.10; P?<?.001) but remained significant beyond 1 year after new-onset AF (adjusted HR, 1.42; 95% CI, 1.18-1.71; P?<?.001), and a trend toward an increased cancer mortality was observed (adjusted HR, 1.32; 95% CI, 0.98-1.79; P?=?.07). In contrast, among women with new-onset cancer, the relative risk of AF was increased only within the first 3 months (HR, 4.67; 95% CI, 2.85-7.64; P?<?.001) but not thereafter (HR, 1.15; 95% CI, 0.95-1.39; P?=?.15). CONCLUSIONS AND RELEVANCE:In this large, initially healthy cohort, women with new-onset AF had an elevated cancer risk beyond 1 year of AF diagnosis. Shared risk factors and/or common systemic disease processes might underlie this association.

Project description:Importance:Atrial fibrillation (AF) is the most common arrhythmia affecting 1% of the population. Young individuals with AF have a strong genetic association with the disease, but the mechanisms remain incompletely understood. Objective:To perform large-scale whole-genome sequencing to identify genetic variants related to AF. Design, Setting, and Participants:The National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine Program includes longitudinal and cohort studies that underwent high-depth whole-genome sequencing between 2014 and 2017 in 18?526 individuals from the United States, Mexico, Puerto Rico, Costa Rica, Barbados, and Samoa. This case-control study included 2781 patients with early-onset AF from 9 studies and identified 4959 controls of European ancestry from the remaining participants. Results were replicated in the UK Biobank (346?546 participants) and the MyCode Study (42?782 participants). Exposures:Loss-of-function (LOF) variants in genes at AF loci and common genetic variation across the whole genome. Main Outcomes and Measures:Early-onset AF (defined as AF onset in persons <66 years of age). Due to multiple testing, the significance threshold for the rare variant analysis was P?=?4.55?×?10-3. Results:Among 2781 participants with early-onset AF (the case group), 72.1% were men, and the mean (SD) age of AF onset was 48.7 (10.2) years. Participants underwent whole-genome sequencing at a mean depth of 37.8 fold and mean genome coverage of 99.1%. At least 1 LOF variant in TTN, the gene encoding the sarcomeric protein titin, was present in 2.1% of case participants compared with 1.1% in control participants (odds ratio [OR], 1.76 [95% CI, 1.04-2.97]). The proportion of individuals with early-onset AF who carried a LOF variant in TTN increased with an earlier age of AF onset (P value for trend, 4.92?×?10-4), and 6.5% of individuals with AF onset prior to age 30 carried a TTN LOF variant (OR, 5.94 [95% CI, 2.64-13.35]; P?=?1.65?×?10-5). The association between TTN LOF variants and AF was replicated in an independent study of 1582 patients with early-onset AF (cases) and 41?200 control participants (OR, 2.16 [95% CI, 1.19-3.92]; P?=?.01). Conclusions and Relevance:In a case-control study, there was a statistically significant association between an LOF variant in the TTN gene and early-onset AF, with the variant present in a small percentage of participants with early-onset AF (the case group). Further research is necessary to understand whether this is a causal relationship.

Dataset Information

Association between familial atrial fibrillation and risk of new-onset atrial fibrillation.

Publications

Association between familial atrial fibrillation and risk of new-onset atrial fibrillation.

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