Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium.

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF).

Temporal Associations Between Smoking and Cardiovascular Disease, 1971 to 2006 (from the Framingham Heart Study).

Smoking has consistently been related to cardiovascular risk. Public health efforts have yielded reduced smoking prevalence and gains in cardiovascular disease (CVD) prevention. We hypothesized that the contribution of tobacco to CVD risk would be attenuated over prospective decades (1971 to 2006) in a community-based cohort.

Incidence rates, correlates, and prognosis of electrocardiographic P-wave abnormalities - a nationwide population-based study.

Background: Scant data exist on incidence rates, correlates, and prognosis of electrocardiographic P-wave abnormalities in the general population.

Methods: We recorded ECG and measured conventional cardiovascular risk factors in 5667 Finns who were followed up for incident atrial fibrillation (AF). We obtained repeat ECGs from 3089 individuals 11years later.

Short-Term Exposure to Ambient Air Pollution and Biomarkers of Systemic Inflammation: The Framingham Heart Study.

Objective: The objective of this study is to examine associations between short-term exposure to ambient air pollution and circulating biomarkers of systemic inflammation in participants from the Framingham Offspring and Third Generation cohorts in the greater Boston area.

Approach And Results: We included 3996 noncurrent smoking participants (mean age, 53.6 years; 54% women) who lived within 50 km from a central air pollution monitoring site in Boston, MA, and calculated the 1- to 7-day moving averages of fine particulate matter (diameter<2.

Prevalence, Correlates, and Prognosis of Healthy Vascular Aging in a Western Community-Dwelling Cohort: The Framingham Heart Study.

Hypertension and increased vascular stiffness are viewed as inevitable parts of aging. To elucidate whether the age-related decrease in vascular function is avoidable, we assessed the prevalence, correlates, and prognosis of healthy vascular aging (HVA) in 3196 Framingham Study participants aged ≥50 years. We defined HVA as absence of hypertension and pulse wave velocity <7.

Burden of Psychosocial and Cognitive Impairment in Patients With Atrial Fibrillation.

Background: Impairments in psychosocial status and cognition relate to poor clinical outcomes in patients with atrial fibrillation (AF). However, how often these conditions co-occur and associations between burden of psychosocial and cognitive impairment and quality of life (QoL) have not been systematically examined in patients with AF.

Methods: A total of 218 patients with symptomatic AF were enrolled in a prospective study of AF and psychosocial factors between May 2013 and October 2014 at the University of Massachusetts Medical Center.

Cardiometabolic Traits and Systolic Mechanics in the Community.

Background: Obesity and cardiometabolic dysfunction are associated with increased risk of heart failure and other cardiovascular diseases. We sought to examine the association of cardiometabolic traits with left ventricular (LV) cardiac mechanics. We hypothesized that specific obesity-related phenotypes are associated with distinct aspects of LV strain.

Relations of Liver Fat With Prevalent and Incident Atrial Fibrillation in the Framingham Heart Study.

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.

Pericardial fat volume and incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis and Jackson Heart Study.

Objective: To determine whether greater pericardial fat volume would be associated with increased risk of incident atrial fibrillation (AF).

Methods: In the Multi-Ethnic Study of Atherosclerosis and Jackson Heart Study, pericardial fat volume was quantified by computed tomography. Incident AF was identified from discharge diagnosis codes, study electrocardiograms, and Medicare claims.

Residential proximity to major roads, exposure to fine particulate matter and aortic calcium: the Framingham Heart Study, a cohort study.

Objectives: Traffic and ambient air pollution exposure are positively associated with cardiovascular disease, potentially through atherosclerosis promotion. Few studies have assessed associations of these exposures with thoracic aortic calcium Agatston score (TAC) or abdominal aortic calcium Agatston score (AAC), systemic atherosclerosis correlates. We assessed whether living close to a major road and residential fine particulate matter (PM) exposure were associated with TAC and AAC in a Northeastern US cohort.

Relations of Arterial Stiffness With Postural Change in Mean Arterial Pressure in Middle-Aged Adults: The Framingham Heart Study.

Impaired regulation of blood pressure on standing can lead to adverse outcomes, including falls, syncope, and disorientation. Mean arterial pressure (MAP) typically increases on standing; however, an insufficient increase or a decline in MAP on standing may result in decreased cerebral perfusion. Orthostatic hypotension has been reported in older people with increased arterial stiffness, whereas the association between orthostatic change in MAP and arterial stiffness in young- to middle-aged individuals has not been examined.

The association of chronic kidney disease and microalbuminuria with heart failure with preserved vs. reduced ejection fraction.

Aims: Chronic kidney disease (CKD) and microalbuminuria are associated with incident heart failure (HF), but their relative contributions to HF with preserved vs. reduced EF (HFpEF and HFrEF) are unknown. We sought to evaluate the associations of CKD and microalbuminuria with incident HF subtypes in the community-based Framingham Heart Study (FHS).

Messenger RNA and MicroRNA transcriptomic signatures of cardiometabolic risk factors.

Background: Cardiometabolic (CM) risk factors are heritable and cluster in individuals. We hypothesized that CM risk factors are associated with multiple shared and unique mRNA and microRNA (miRNA) signatures. We examined associations of mRNA and miRNA levels with 6 CM traits: body mass index, HDL-cholesterol and triglycerides, fasting glucose, and systolic and diastolic blood pressures through cross-sectional analysis of 2812 Framingham Heart Study who had whole blood collection for RNA isolation for mRNA and miRNA expression studies and who consented to genetic research.

Methylome-wide Association Study of Atrial Fibrillation in Framingham Heart Study.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, but little is known about the molecular mechanisms associated with AF arrhythmogenesis. DNA methylation is an important epigenetic mechanism that regulates gene expression and downstream biological processes. We hypothesize that DNA methylation might play an important role in the susceptibility to develop AF.

Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels.

Background: Genomic analyses have suggested that the LPA gene and its associated plasma biomarker, lipoprotein(a) (Lp[a]), represent a causal risk factor for coronary heart disease (CHD). As such, lowering Lp(a) levels has emerged as a therapeutic strategy. Beyond target identification, human genetics may contribute to the development of new therapies by defining the full spectrum of beneficial and adverse consequences and by developing a dose-response curve of target perturbation.

Serum brain-derived neurotrophic factor and risk of atrial fibrillation.

Unlabelled: Brain-derived neurotrophic factor (BDNF) is expressed by endothelial cells and can affect cardiovascular function. We examined if serum BDNF was associated with risk of incident atrial fibrillation (AF) in the Framingham Heart Study.

Methods: We studied individuals without an AF diagnosis at baseline from the Framingham original and offspring cohorts.

Cluster Individuals Based on Phenotype and Determine the Risk for Atrial Fibrillation in the PREVEND and Framingham Heart Study Populations.

Background: Risk prediction of atrial fibrillation (AF) is of importance to improve the early diagnosis and treatment of AF. Latent class analysis takes into account the possible existence of classes of individuals each with shared risk factors, and maybe a better method of incorporating the phenotypic heterogeneity underlying AF.

Methods And Findings: Two prospective community-based cohort studies from Netherlands and United States were used.

Gene-gene Interaction Analyses for Atrial Fibrillation.

Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility.

Genome-wide Association Study of Parental Life Span.

Background: Having longer lived parents has been shown to be an important predictor of health trajectories and life span. As such, parental life span is an important phenotype that may uncover genes that affect longevity.

Methods: A genome-wide association study of parental life span in participants of European and African ancestry from the Health and Retirement Study was conducted.

Gain-of-function mutations in GATA6 lead to atrial fibrillation.

Background: The genetic basis of atrial fibrillation (AF) and congenital heart disease remains incompletely understood.

Objective: We sought to determine the causative mutation in a family with AF, atrial septal defects, and ventricular septal defects.

Methods: We evaluated a pedigree with 16 family members, 1 with an atrial septal defect, 1 with a ventricular septal defect, and 3 with AF; we performed whole exome sequencing in 3 affected family members.

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication.

Trajectories of Risk Factors and Risk of New-Onset Atrial Fibrillation in the Framingham Heart Study.

The associations of long-term patterns of risk factors and the risk of incident atrial fibrillation (AF) are incompletely characterized. Among 4351 Framingham Study participants (mean age 50±11 years at baseline examination, 57% women) from the original and offspring cohorts, we defined longitudinal patterns, referred to as trajectories, of AF risk factors and a composite AF risk score using ≈16 years of data. We used Cox proportional hazards models to examine the association of trajectories to 15-year risk of AF.

Relations of Arterial Stiffness and Brachial Flow-Mediated Dilation With New-Onset Atrial Fibrillation: The Framingham Heart Study.

The relations of measures of arterial stiffness, pulsatile hemodynamic load, and endothelial dysfunction to atrial fibrillation (AF) remain poorly understood. To better understand the pathophysiology of AF, we examined associations between noninvasive measures of vascular function and new-onset AF. The study sample included participants aged ≥45 years from the Framingham Heart Study offspring and third-generation cohorts.

Plasma Fibroblast Growth Factor 23: Clinical Correlates and Association With Cardiovascular Disease and Mortality in the Framingham Heart Study.

Background: Fibroblast growth factor 23 (FGF23) is emerging as a novel biomarker of bone metabolism, chronic kidney disease, and cardiovascular disease (CVD). However, its clinical correlates and potential predictive role in a community-based setting are incompletely understood.

Methods And Results: We evaluated participants of the Framingham Heart Study (seventh examination cycle of the Offspring cohort plus second examination cycle of the multiethnic Omni cohort) to identify clinical correlates of plasma FGF23 (N=3236) and examine its cross-sectional association with vascular function (N=2209), and longitudinal association with 10-year incidence of CVD (N=2823), and all-cause mortality (N=3223).