Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample: The CHRIS Study.
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SUBMITTER: Emmert DB
PROVIDER: S-EPMC8615508 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Massachusetts General Hospital Atrial Fibrillation Study
| PRJNA297616 | ENA
Project description:BackgroundInitial evidence suggests that depressive symptoms are more frequent in patients with atrial fibrillation. Data from the general population are limited.Methods and resultsIn 10,000 individuals (mean age 56±11 years, 49.4% women) of the population-based Gutenberg Health Study we assessed depression by the Patient Health Questionnaire (PHQ-9) and a history of depression in relation to manifest atrial fibrillation (n = 309 cases). The median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in atrial fibrillation individuals versus 3 (2/6) individuals without atrial fibrillation, P(X2-Test) = 0.32. Multivariable regression analyses of the severity of depressive symptoms in relation to atrial fibrillation in cardiovascular risk factor adjusted models revealed a relation of PHQ-9 values and atrial fibrillation (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08; P = 0.023). The association was stronger for the somatic symptom dimension of depression (OR 1.08, 95% CI 1.02-1.15; P = 0.0085) than for cognitive symptoms (OR 1.05, 95% CI 0.98-1.11; P = 0.15). Results did not change markedly after additional adjustment for heart failure, partnership status or the inflammatory biomarker C-reactive protein. Both, self-reported physical health status, very good/good versus fair/bad, (OR 0.54, 95% CI 0.41-0.70; P<0.001) and mental health status (OR 0.61 (0.46-0.82); P = 0.0012) were associated with atrial fibrillation in multivariable-adjusted models.ConclusionsIn a population-based sample we observed a higher burden of depressive symptoms driven by somatic symptom dimensions in individuals with atrial fibrillation. Depression was associated with a worse perception of physical or mental health status. Whether screening and treatment of depressive symptoms modulates disease progression and outcome needs to be shown.
| S-EPMC3850915 | biostudies-literature
Project description:BackgroundDifferent biological pathways have been related to atrial fibrillation (AF). Novel biomarkers capturing inflammation, oxidative stress, and neurohumoral activation have not been investigated comprehensively in AF.Methods and resultsIn the population-based Gutenberg Health Study (n = 5000), mean age 56 ± 11 years, 51% males, we measured ten biomarkers representing inflammation (C-reactive protein, fibrinogen), cardiac and vascular function (midregional pro adrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [Nt-proBNP], sensitive troponin I ultra [TnI ultra], copeptin, and C-terminal pro endothelin-1), and oxidative stress (glutathioneperoxidase-1, myeloperoxidase) in relation to manifest AF (n = 161 cases). Individuals with AF were older, mean age 64.9 ± 8.3, and more often males, 71.4%. In Bonferroni-adjusted multivariable regression analyses strongest associations per standard deviation increase in biomarker concentrations were observed for the natriuretic peptides Nt-proBNP (odds ratio [OR] 2.89, 99.5% confidence interval [CI] 2.14-3.90; P<0.0001), MR-proANP (OR 2.45, 99.5% CI 1.91-3.14; P<0.0001), the vascular function marker MR-proADM (OR 1.54, 99.5% CI 1.20-1.99; P<0.0001), TnI ultra (OR 1.50, 99.5% CI 1.19-1.90; P<0.0001) and. fibrinogen (OR 1.44, 99.5% CI 1.19-1.75; P<0.0001). Based on a model comprising known clinical risk factors for AF, all biomarkers combined resulted in a net reclassification improvement of 0.665 (99.3% CI 0.441-0.888) and an integrated discrimination improvement of >13%.ConclusionsIn conclusion, in our large, population-based study, we identified novel biomarkers reflecting vascular function, MR-proADM, inflammation, and myocardial damage, TnI ultra, as related to AF; the strong association of natriuretic peptides was confirmed. Prospective studies need to examine whether risk prediction of AF can be enhanced beyond clinical risk factors using these biomarkers.
| S-EPMC4234420 | biostudies-literature
Project description:BackgroundAtrial fibrillation (AF) is the most common age-related cardiac arrhythmia. The etiology underlying AF is still largely unknown. At the intersection of the innate immune system and hemostasis, immunothrombosis may be a possible cause of atrial remodeling, and therefore be an underlying cause of AF.MethodsFrom 1990 to 2014, we followed participants aged 55 and over, free from AF at inclusion. Immunothrombosis factors fibrinogen, von Willebrand factor, ADAMTS13, and neutrophil extracellular traps (NETs) levels were measured at baseline. Participants were followed until either onset of AF, loss-to-follow-up, or reaching the end-date of 01-01-2014. Cox proportional hazard modelling was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for cardiovascular risk factors.ResultsWe followed 6174 participants (mean age 69.1 years, 57% women) for a median follow-up time of 12.8 years. 364 men (13.7%, incidence rate 13.0/1000 person-years) and 365 women (10.4%, incidence rate 8.9/1000 person-years) developed AF. We found no significant association between markers of immunothrombosis and new-onset AF after adjusting for cardiovascular risk factors [HR 1.00 (95% CI 0.93-1.08) for fibrinogen, 1.04 (0.97-1.12) for von Willebrand factor, 1.00 (1.00-1.01) for ADAMTS13, and 1.01 (0.94-1.09) for NETs]. In addition, we found no differences in associations between men and women.ConclusionWe found no associations between markers of immunothrombosis and new-onset AF in the general population. Inflammation and immunothrombosis may be associated with AF through other cardiovascular risk factors or predisposing conditions of AF. Our findings challenge the added value of biomarkers in AF risk prediction.
| S-EPMC8766396 | biostudies-literature
Project description:MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the relationship differs by sex. We therefore aimed to determine the (sex-specific) association between plasma circulatory miRNAs and AF at the population level. Plasma levels of miRNAs were measured using a targeted next-generation sequencing method in 1999 participants from the population-based Rotterdam Study. Logistic regression and Cox proportional hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for cardiovascular risk factors. We further examined the link between predicted target genes of the identified miRNAs. The mean age was 71.7 years (57.1% women), 98 participants (58 men and 40 women) had prevalent AF at baseline. Moreover, 196 participants (96 men and 100 women) developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with the odds of prevalent AF among men (odds ratio, 95% confidence interval, 0.39, 0.24-0.66, p-value = 0.000248). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of a number of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Plasma levels of miR-4798-3p were significantly associated with the odds of prevalent AF among men. Several target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.
| S-EPMC8775308 | biostudies-literature
Project description:Although exercise prevents cardiovascular disease and mortality, vigorous exercise and endurance athletics can cause atrial fibrillation (AF). However, no large cohort study has assessed the relationship between physical activity and AF in the general population. We assessed the effect of physical activity at different energy expenditures on the incidence of AF. We studied 501,690 individuals without pre-existing AF (mean age, 47.6 ± 14.3 years; 250,664 women [50.0%]) included in the Korean National Health Insurance Service database. The physical activity level was assessed using a standardized self-reported questionnaire at baseline. During a median follow-up of 4 years, 3,443 participants (1,432 women [41.6%]) developed AF. The overall incidence of AF at follow-up was 1.79 per 1,000 person-years. The subjects who met the recommended physical activity level (500-1,000 metabolic equivalent task [MET] minutes/week) had a 12% decreased AF risk (adjusted hazard ratio [HR]: 0.88, 95% confidence interval [CI]: 0.80-0.97), but not the insufficiently (1-500 MET-minutes/week; HR: 0.94, 95% CI: 0.86-1.03) and highly active subjects (≥1,000 MET-minutes/week; HR: 0.93, 95% CI: 0.85-1.03). The recommended minimum key target range of physical activity level was associated with the maximum benefit for reduced AF risk in the general population. The dose-response relationship between physical activity level and AF risk showed a U-shaped pattern. Although exceeding the key target range attenuated this benefit, it did not increase the AF risk beyond that during inactivity.
| S-EPMC6744571 | biostudies-literature
Project description:Background The incidences of atrial fibrillation (AF) and chronic kidney disease (CKD) are increasing, and AF is prevalent in patients with CKD. However, few studies have investigated the incidence or association of AF in a large CKD population from a longitudinal study. Methods and Results From a nationwide cohort, a total of 4 827 987 Korean individuals without prior AF, who received biennial health checkups provided by the National Health Insurance Service between 2009 and 2012 in Korea, were analyzed. Incidence of AF was ascertained through the end of 2018. During a median follow-up of 8.1 years, the annual incidence rate of AF was 1.17 per 1000 person-years among subjects without CKD, 1.55 for stage 1 CKD, 1.86 for stage 2 CKD, 2.1 for stage 3 CKD, and 4.33 for stage 4 CKD. In Fine-Gray regression models, CKD was associated with an increased risk of AF; the adjusted hazard ratios and 95% CIs of AF occurrence were 1.77 (1.69-1.85), 1.85 (1.80-1.91), 1.99 (1.95-2.04), and 4.04 (3.07-5.33) in individuals with CKD stages 1, 2, 3, and 4, respectively, compared with non-CKD. The association between CKD and incident AF remained statistically significant after adjustment for multiple confounding factors and was consistent across subgroups stratified by sex and age. Conclusions CKD is associated with an increased incidence of AF. Even mild CKD is associated with incident AF, and there was a stepwise increase in the risk of incident AF with a decrease in renal function.
| S-EPMC10227274 | biostudies-literature
Project description:ObjectiveAtrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF.MethodsIn this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression.ResultsMean age was 65 (58-71) years, 179 (43%) were female. Follow-up was 2.2 (1.6-2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression.ConclusionIn patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed.Trial registration numberNCT02726698.
| S-EPMC9872250 | biostudies-literature
Project description:BackgroundAlthough proteinuria has been associated with incident atrial fibrillation (AF) in Western countries, the association has not been investigated in the general Japanese population.MethodsParticipants aged ≥40 years who underwent the Japanese specific health check-up in Kanazawa City in 2013 and who completed a urine dipstick test were included in this study. Exposure was considered as presence or absence of proteinuria (≥1+). The outcome was incident AF confirmed by 12-lead electrocardiography. The Cox proportional hazard model was used to compute hazard ratio (HR) of proteinuria (≥1+) for incident AF after adjustment for traditional risk factors. We also completed stratified analyses by baseline characteristics.ResultsA total of 37,910 participants aged ≥40 years were included (mean age: 72.3 years, male sex: 37%). Proteinuria ≥1+ was observed in 2.765 (7.3%) participants. During a median follow-up period of 5 years, 708 incident AF cases were observed. Proteinuria ≥1+ was associated with incident AF (HR, 1.47: 95% confidence interval, 1.18-1.84) after covariate adjustment. Stratified analysis demonstrated that the association of proteinuria with AF was stronger in participants <75 years [HR 1.89 (95% CI 1.32-2.70)] compared with those ≥75 years [HR 1.27 (95% CI 0.95-1.69)] (interaction p-value=0.02).ConclusionsProteinuria was significantly associated with incident AF in the general Japanese population. The evaluation of proteinuria using urine dipstick test may be useful in the evaluation of incident AF, especially in younger general population.
| S-EPMC7924545 | biostudies-literature
Project description:BackgroundThe P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD.MethodsFifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies.ResultsWe identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (TTN, CAND2, SCN10A, PITX2, CAV1, SYNPO2L, SOX5, TBX5, MYH6, RPL3L). The top variants at known sarcomere genes (TTN, MYH6) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A) were associated with longer PWD but lower AF risk.ConclusionsOur results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.
| S-EPMC7578098 | biostudies-literature