Person:

Lubitz, Steven

Background: Atrial fibrillation (AF) involves substantial electrophysiological, structural and contractile remodeling. We hypothesize that characterizing gene expression might uncover important pathways related to AF. Methods and Results: We performed genome-wide whole blood transcriptomic profiling (Affymetrix Human Exon 1.0 ST Array) of 2446 participants (mean age 66±9 years, 55% women) from the Offspring cohort of Framingham Heart Study. The study included 177 participants with prevalent AF, 143 with incident AF during up to 7 years follow up, and 2126 participants with no AF. We identified seven genes statistically significantly up-regulated with prevalent AF. The most significant gene, PBX1 (P = 2.8×10−7), plays an important role in cardiovascular development. We integrated differential gene expression with gene-gene interaction information to identify several signaling pathways possibly involved in AF-related transcriptional regulation. We did not detect any statistically significant transcriptomic associations with incident AF. Conclusion: We examined associations of gene expression with AF in a large community-based cohort. Our study revealed several genes and signaling pathways that are potentially involved in AF-related transcriptional regulation.

Background: Advancing age is a prominent risk factor for atrial fibrillation (AF). Shorter telomere length is a biomarker of biological aging, but the link between shorter telomere length and increased risk of AF remains unclear. We examined the association between shorter leukocyte telomere length (LTL) and incident AF. Methods and Results: We included AF‐free participants from the observational Framingham Heart Study Offspring cohort from 1995 to 1998, who had LTL measurements. We examined the association between baseline LTL and incident AF with multivariable Cox models adjusted for age, sex, current smoking, height, weight, systolic and diastolic blood pressure, use of antihypertensive medication, diabetes mellitus, history of myocardial infarction, and history of heart failure. The study sample comprised 1143 AF‐free participants (52.8% women), with mean age of 60±8 years. The mean LTL at baseline was 6.95±0.57 kb. During 15.1±4.2 years mean follow‐up, 184 participants (64 women) developed AF. Chronological age was associated with increased risk of AF (hazard ratio per 10‐year increase, 2.16; 95% confidence interval, 1.71–2.72). There was no significant association between LTL and incident AF (hazard ratio per 1 SD decrease LTL, 1.01; 95% confidence interval, 0.86–1.19). Our study was observational in nature; hence, we could not exclude residual confounding and we were unable to establish causal pathways. Conclusions: In our moderate‐sized community‐based cohort, we did not find evidence for a significant association between LTL and risk of incident AF.

Background: Obesity is an important risk factor for nonalcoholic fatty liver disease and atrial fibrillation (AF). Less is known about the relations between nonalcoholic fatty liver disease and AF. We sought to evaluate the association between fatty liver and prevalent and incident AF in the community. Methods and Results: We examined Framingham Heart Study participants who underwent a study‐directed computed tomography scan, had hepatic steatosis (HS) evaluated, and did not report heavy alcohol use between 2002 and 2005. We evaluated cross‐sectional associations between liver fat and prevalent AF with logistic regression models. We assessed the relations between liver fat and incident AF during 12‐year follow‐up with Cox proportional hazards models. Of 2122 participants (53% women; mean age, 59.0±9.6 years), 20% had HS. AF prevalence (n=62) among individuals with HS was 4% compared to 3% among those without HS. There was no significant association between HS (measured as continuous or dichotomous variables) and prevalent AF in age‐ and sex‐adjusted or multivariable‐adjusted models. Incidence of AF (n=153) among participants with and without HS was 8.7 cases and 7.8 cases per 1000 person‐years, respectively. In age‐ and sex‐adjusted and multivariable‐adjusted models, there were no significant associations between continuous or dichotomous measures of HS and incident AF. Conclusions: In our community‐based, longitudinal cohort study, liver fat by computed tomography scan was not significantly associated with increased prevalence or incidence of AF over 12 years of follow‐up.