Genetic Determinants of Increased Body Mass Index Partially Mediate the Effect of Elevated Birth Weight on the Increased Risk of Atrial Fibrillation.
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SUBMITTER: Chen S
PROVIDER: S-EPMC8377229 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Few if any studies have assessed the relationship between birth weight and incident atrial fibrillation (AF).From 1993 to 2009, we prospectively followed 27 982 women who were >45 years of age and free of cardiovascular disease and AF at baseline. Information on birth weight was categorized into 5 different categories: <2.5, 2.5 to 3.2, 3.2 to 3.9, 3.9 to 4.5, and >4.5 kg. The primary outcome was time to incident AF. During 14.5 years of follow-up, 735 AF events occurred. Age-adjusted incidence rates for incident AF from the lowest to the highest birth weight category were 1.45, 1.82, 1.88, 2.57, and 2.55 events per 1000 person-years of follow-up. After multivariable adjustment, hazard ratios for incident AF across increasing birth weight categories were 1.0, 1.30 (95% confidence interval [CI], 0.96 to 1.75), 1.28 (95% CI, 0.96 to 1.69), 1.70 (95% CI, 1.23 to 2.37), and 1.71 (95% CI, 1.12 to 2.61) (P for linear trend=0.002). Adding body mass index, blood pressure, and diabetes mellitus at study entry did not have a large effect on these estimates (P for linear trend=0.004). In contrast, including height in the multivariable model substantially attenuated the relationship between birth weight and AF (P for linear trend=0.17), and additional adjustment for maximum weight in young adulthood further attenuated this association (multivariable-adjusted hazard ratio across birth weight categories, 1.0, 1.27 [95% CI, 0.94 to 1.71], 1.10 [95% CI, 0.83 to 1.46], 1.41 [95% CI, 1.01 to 1.96], and 1.29 [95% CI, 0.84 to 1.98]; P for linear trend=0.23).Birth weight is significantly associated with incident AF among women, suggesting that early life determinants may play an important role in the pathogenesis of AF.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
| S-EPMC2927709 | biostudies-literature
Project description:IntroductionAtrial fibrillation is associated with hyperthyroidism. Within the euthyroid range, it is also associated with high thyroxine (fT4), but not with thyrotropin (TSH). We aim to describe differences in thyroid regulation, measured by the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), between patients with atrial fibrillation and the general population.Materials and methodsThyroid parameters (PTFQI, TSH, and fT4) of a sample of 84 euthyroid subjects with atrial fibrillation (cases) were compared to a reference sample of euthyroid healthcare patients (controls). We calculated age and sex adjusted ORs for atrial fibrillation across tertiles of these parameters. Also, within cases, we studied thyroid parameters association with clinical characteristics of the atrial fibrillation.ResultsAfter adjusting for age and sex, fT4 and PTFQI were higher in subjects with atrial fibrillation when compared to the general sample (p<0.01 and p=0.01, respectively). Atrial fibrillation ORs of the third versus the first PTFQI tertile was 1.88(95%CI 1.07,3.42), and there was a gradient across tertiles (p trend=0.02). Among atrial fibrillation patients, we observed that higher PTFQI was associated with sleep apnea/hypopnea syndrome (OSAS) (p=0.03), higher fT4 was associated with the presence of an arrhythmogenic trigger (p=0.02) and with heart failure (p<0.01), and higher TSH was also associated with OSAS (p<0.01).ConclusionsEuthyroid subjects with atrial fibrillation have an elevation of the pituitary TSH-inhibition threshold, measured by PTFQI, with respect to the general population. Within atrial fibrillation patients, high PTFQI was associated with OSAS, and high fT4 with heart failure. These results hint of the existence of a relationship between thyroid regulation and atrial fibrillation.
| S-EPMC9995977 | biostudies-literature
Project description:BackgroundAlthough obesity has been associated with risk of atrial fibrillation (AF), the associations of variability of obesity measures with AF risk are uncertain, and longitudinal studies among Chinese population are still lacking. We aimed to evaluate the impacts of obesity and variability of body mass index (BMI) and waist circumference (WC) on the risk of atrial fibrillation (AF) in a large Chinese cohort study.MethodsA total of 44,135 participants of the Kailuan Study who were free of cancer and cardiovascular disease and underwent three consecutive surveys from 2006 to 2010 were followed for incident AF until 2020. Average BMI and WC over time and variability were calculated. Cox proportional hazards regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of obesity and variability in BMI and WC with AF risk.ResultsDuring a mean follow-up of 9.68 years, there were 410 cases of incident AF. In multivariable-adjusted models, compared with normal BMI/WC, individuals with general obesity and abdominal obesity had increased risk of AF, with corresponding HRs of 1.73 (95% CI: 1.31-2.30) and 1.38 (95% CI: 1.11-1.60), respectively. The short-term elevation in AF risk persisted for the obese even after adjustment for updated biologic intermediaries and weight. Variability in BMI and WC were not associated with the risk of AF. The restricted cubic spline models indicated significant linear relationships between levels of WC and BMI and risk of AF.ConclusionsElevated levels of BMI and WC were associated with an increased risk of AF, whereas variability in BMI and WC were not. Therefore, achieving optimal levels of BMI and WC could be valuable in AF prevention.
| S-EPMC9241273 | 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:Background: Genomic and experimental studies suggest a role for PITX2 in atrial fibrillation (AF). To assess whether this association is relevant for recurrent AF in patients, we tested whether left atrial PITX2 affects recurrent AF after AF ablation. Methods: mRNA concentrations of PITX2 and its cardiac isoform, PITX2c, were quantified in left atrial appendages (LAA) from patients undergoing thoracoscopic AF ablation, either in whole LAA tissue (n=83) or in LAA cardiomyocytes (n=52), and combined with clinical parameters to predict AF recurrence. Literature suggests bone morphogenetic protein 10 (BMP10) as a PITX2-repressed, atrial-specific, secreted protein. BMP10 plasma concentrations were combined with eleven cardiovascular biomarkers and clinical parameters to predict recurrent AF after catheter ablation in 359 patients. Results: Reduced cardiomyocyte PITX2 concentrations, but not whole LAA tissue PITX2, were associated with AF recurrence after thoracoscopic AF ablation (16% decreased recurrence per 2-(ΔΔCt) increase in PITX2). RNA sequencing, qPCR and Western blotting confirmed BMP10 as one of most PITX2-repressed atrial genes. Left atrial size (hazard ratio per mm increase, HR [95%CI] 1.055 [1.028, 1.082], non-paroxysmal AF (HR 1.672 [1.206, 2.318]) and elevated BMP10 (HR 1.339 [CI 1.159, 1.546] per quartile increase) were predictive of recurrent AF. BMP10 outperformed eleven other cardiovascular biomarkers in predicting recurrent AF. Conclusions: Reduced left atrial cardiomyocyte PITX2 and elevated plasma concentrations of the PITX2-repressed, secreted, atrial protein BMP10 identify patients at risk of recurrent AF after ablation.
2020-06-19 | GSE152181 | GEO
Project description:We performed a matched case-control study using a propensity score matching, to assess the association of Th17-related cytokines, including interleukin (IL) 17A (IL-17A), IL-17F, IL-21, IL-22 and IL-6, along with interferon-γ (IFN-γ), IL-10, IL-9, and IL-4, with the risk of AF. A total of 336 patients with AF were matched 1:1 with patients without AF. Plasma levels of cytokines were measured using Luminex xMAP assays. The plasma levels of all examined cytokines were significantly higher in AF patients than controls (P < 0.05), and these cytokines were highly correlated with each other (P < 0.01). A multivariate conditional logistic regression analysis showed that elevated plasma levels of IL-17A, IL-17F, IL-21, IL-22, IFN-γ, IL-10, IL-9 and IL-6 were significantly associated with AF risk independently of potential confounders. There were no significant differences in plasma levels of examined cytokines between paroxysmal and chronic AF patients. IL-17A, IL-21, IL-10 and IL-6 levels were positively correlated with left atrial diameter; IL-17F level was negatively correlated with left ventricle ejection fraction among AF patients (P < 0.05). Elevated plasma levels of Th17-related cytokines were independently associated with increased an risk of AF; hence, Th17-related cytokines may be involved in the pathogenesis of AF.
| S-EPMC4873818 | biostudies-literature
Project description:IntroductionLeft atrial (LA) enlargement is an important risk factor for incident stroke and a key determinant for the success of rhythm control strategies in patients with atrial fibrillation (AF). However, factors associated with LA volume in AF patients remain poorly understood.MethodsPatients with paroxysmal or persistent AF were enrolled in this study. Real time 3-D echocardiography was performed in all participants and analyzed offline in a standardized manner. We performed stepwise backward linear regression analyses using a broad set of clinical parameters to determine independent correlates for 3-D LA volume.ResultsWe included 210 patients (70.9% male, mean age 61±11years). Paroxysmal and persistent AF were present in 95 (45%) and 115 (55%) patients, respectively. Overall, 115 (55%) had hypertension, 11 (5%) had diabetes, and 18 (9%) had ischemic heart disease. Mean indexed LA volume was 36±12ml/m2. In multivariable models, significant associations were found for female sex (β coefficient -10.51 (95% confidence interval (CI) -17.85;-3.16), p = 0.0053), undergoing cardioversion (β 11.95 (CI 5.15; 18.74), p = 0.0006), diabetes (β 14.23 (CI 2.36; 26.10), p = 0.019), body surface area (BSA) (β 34.21 (CI 19.30; 49.12), p<0.0001), glomerular filtration rate (β -0.21 (CI -0.36; -0.06), p = 0.0064) and plasma levels of NT-pro brain natriuretic peptide (NT-proBNP) (β 6.79 (CI 4.05; 9.52), p<0.0001), but not age (p = 0.59) or hypertension (p = 0.42). Our final model explained 52% of the LA volume variability.ConclusionsIn patients with AF, the most important correlates with LA volume are sex, BSA, diabetes, renal function and NT-proBNP, but not age or hypertension. These results may help to refine rhythm control strategies in AF patients.
| S-EPMC5049755 | biostudies-literature
Project description:Atrial fibrillation (AF) is the most common cardiac arrhythmia; however, therapy is suboptimal. We review recent data on dynamics of wave propagation during AF and its mechanistic link to the substrate. Data show that the dominant frequency (DF) increase during transition to persistent AF may be explained by rotor acceleration. We discuss how translation of experimentally derived understanding of the rotors may find its way into the clinic, focusing on studies analyzing spatial distribution of DF in the atria of patients with paroxysmal versus persistent AF, and how that knowledge might contribute to improve the outcome of AF ablation procedures.
| S-EPMC5547895 | biostudies-other
Project description:OBJECTIVE:The aims of this study are to examine the potential association between grandmaternal BMI and grandchild's birth weight (BW) and whether maternal BW and BMI mediate this association. METHODS:Data of 209 grandmother-mother pairs and 355 grandchildren from the Isle of Wight birth cohort in the UK were analyzed using path analysis. RESULTS:An indirect effect of grandmaternal BMI on increasing grandchild's BW was mediated by maternal BW and BMI at age 18 years (indirect effects: ??=?2.3?g/unit increase in grandmaternal BMI via maternal BW and ??=?4.4 g via maternal BMI; P?=?0.04). These two mediating effects of maternal BW and BMI confounded one another. Grandmaternal smoking during pregnancy had an indirect effect on decreasing grandchild's BW, dependent on maternal smoking during pregnancy and BW (indirect effects: ??=?-36.1 g compared with nonsmoking grandmothers via maternal smoking during pregnancy and ??=?-27.2 g via maternal BW; P?=?0.005). Neither direct effect between grandmaternal BMI and grandchild's BW nor that between grandmaternal smoking during pregnancy and grandchild's BW was statistically significant. CONCLUSIONS:Larger grandmaternal BMI indirectly increased grandchild's BW via maternal BW and BMI. Grandmaternal smoking during pregnancy indirectly reduced grandchild's BW via maternal smoking during pregnancy and BW.
| S-EPMC7042056 | biostudies-literature
Project description:ObjectivesWeight at birth is usually considered as an indicator of the health status of a given society. As a result this study was designed to investigate the association between birth weight and maternal factors such as gestational weight gain, pre-pregnancy BMI and socio-economic status in Northern Ghana.MethodsThe study was a facility-based cross-sectional survey conducted in two districts in the Northern region of Ghana. These districts were purposively sampled to represent a mix of urban, peri-urban and rural population. The current study included 419 mother-infant pairs who delivered at term (37-42 weeks). Mother's height, pre-pregnancy weight and weight changes were generated from the antenatal records. Questionnaires were administered to establish socio-economic and demographic information of respondents. Maternal factors associated with birth weight were examined using multiple and univariate regressions.ResultsThe mothers were generally well nourished before conception (Underweight 3.82%, Normal 57.76%, Overweight 25.06% and Obesity 13.37%) but approximately half of them could not gain adequate weight according to Institute of Medicine recommendations (Low weight gain 49.64%, Adequate weight gain 42.96% and Excessive weight gain 7.40%). Infants whose mothers had excess weight gain were 431g (95% CI 18-444) heavier compared to those whose mothers gained normal weight, while those whose mothers gained less were 479g (95% CI -682- (-276) lighter. Infants of mothers who were overweight and obese before conception were 246g (95% CI 87-405) and 595g (95% CI 375-815) respectively heavier than those of normal mothers, whereas those whose mothers were underweight were 305g (95% CI -565 -(-44) lighter. The mean birth weight observed was 2.98 ± 0.68 kg.ConclusionOur findings show that pre-pregnancy body mass index and weight gain during pregnancy influence birth weight. Therefore, emphasis should be placed on counseling and assisting pregnant women to stay within the recommended weight gain ranges.
| S-EPMC4539219 | biostudies-literature