Genetic Obesity and the Risk of Atrial Fibrillation

Chatterjee, Neal A.; Giulianini, Franco; Geelhoed, Bastiaan; Lunetta, Kathryn L.; Misialek, Jeffrey R.; Niemeijer, Maartje N.; Rienstra, Michiel; Rose, Lynda M.; Smith, Albert V.; Arking, Dan E.; Ellinor, Patrick T.; Heeringa, Jan; Lin, Honghuang; Lubitz, Steven A.; Soliman, Elsayed Z.; Verweij, Niek; Alonso, Álvaro; Benjamin, Emelia J.; Gudnason, Vilmundur; Stricker, Bruno H. Ch.; Harst, Pim van der; Chasman, Daniel I.; Albert, Christine M.

doi:10.1161/circulationaha.116.024921

Cited by 99 publications

(26 citation statements)

References 72 publications

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“…This approach can be a strong alternative for better understanding the sex-specific nature of the associations of risk factors with AF. A recent large-scale Mendelian randomization study has confirmed a causal relationship between BMI and incident AF (63). However, sex differences were not reported.…”

Section: Discussionmentioning

confidence: 98%

Differences in Epidemiology and Risk Factors for Atrial Fibrillation Between Women and Men

Kavousi

2020

Front. Cardiovasc. Med.

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Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is one of the most frequent cardiovascular diseases among both women and men. Although age-adjusted AF incidence and prevalence is larger among men, women are older at the time of AF diagnosis and have larger risk for AF-associated adverse outcomes such as morality and stroke. Based on evidence from epidemiological studies, elevated body mass index seems to confer a higher risk of AF among men. However, evidence regarding sex differences in the association between diabetes mellitus, elevated blood pressure, and dysglycemia with AF remains conflicting. While men with AF have larger burden of coronary artery disease, women with AF tend to have a larger prevalence of heart failure and valvular heart disease. Recently, several women-specific risk factors including pregnancy and its complications and number of children have been associated with AF. Earlier age at menopause, despite being a strong marker of adverse cardiometabolic risk, does not seem to be associated with increased risk of AF. To reduce the AF burden in both genders, better understanding of the differences between women and men with regard to AF is central. Large-scale studies are needed to separately investigate and report on women and men. Besides observations from epidemiological and clinical studies, to improve our understanding of sexual dimorphism in AF, sufficiently large genome-wide association studies as well as well-powered Mendelian randomization studies are essential to shed light on the sex-specific nature of the associations of risk factors with AF.

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Section: Discussionmentioning

confidence: 98%

Differences in Epidemiology and Risk Factors for Atrial Fibrillation Between Women and Men

Kavousi

2020

Front. Cardiovasc. Med.

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“…One possibility is that the associated comorbidities of type 2 diabetes, namely hypertension and obesity, are the causal link between type 2 diabetes and atrial fibrillation. In fact, a recent Mendelian randomisation analysis showed a causal relationship between BMI and incident atrial fibrillation [11].…”

Section: Discussionmentioning

confidence: 99%

No evidence of a causal association of type 2 diabetes and glucose metabolism with atrial fibrillation

et al. 2019

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Aims/hypothesis Several epidemiological studies have shown an increased risk of atrial fibrillation in individuals with type 2 diabetes or milder forms of dysglycaemia. We aimed to assess whether this relation is causal using a Mendelian randomisation approach. Methods Two-sample Mendelian randomisation was used to obtain estimates of the influence of type 2 diabetes, fasting blood glucose (FBG), and HbA 1c on the risk of atrial fibrillation. Instrumental variables were constructed using available summary statistics from meta-analyses of genome-wide association studies (GWAS) for type 2 diabetes and associated phenotypes. Pleiotropic SNPs were excluded from the analyses. The most recent GWAS meta-analysis summary statistics for atrial fibrillation, which included over 1 million individuals (approximately 60,000 individuals with atrial fibrillation) was used for outcome analysis. Results Neither type 2 diabetes (OR 1.01 [95% CI 0.98, 1.03]; p = 0.37), nor FBG (OR 0.95 [95% CI 0.82, 1.09] per mmol/l; p = 0.49) or HbA 1c (OR 1.01 [95% CI, 0.85, 1.17] per mmol/mol [%]; p = 0.88) were associated with atrial fibrillation in Mendelian randomisation analyses. We had >80% statistical power to detect ORs of 1.08, 1.06 and 1.09 or larger for type 2 diabetes, FBG and HbA 1c , respectively, for associations with atrial fibrillation. Conclusions/interpretation This Mendelian randomisation analysis does not support a causal role of clinical significance between genetically programmed type 2 diabetes, FBG or HbA 1c and development of atrial fibrillation. These data suggest that drug treatment to reduce dysglycaemia is unlikely to be an effective strategy for atrial fibrillation prevention. Data availability The datasets analysed during the current study are available from the following repository: Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al (2018) GWAS summary statistics for AF (N=60,620 AF cases and 970,216 controls).

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“…In a Mendelian randomization analysis of genetic alleles associated with obesity, Chatterjee et al 10 explored the relationship between obesity and AF in 51 646 patients of European decent. They found strong support for a causal link between obesity and AF and a basis for public health interventions.…”

Section: Genetics Of Afmentioning

confidence: 99%

Year in Review in Cardiac Electrophysiology

Tzou

Hussein

Madhavan

et al. 2018

Circ: Arrhythmia and Electrophysiology

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1 In the past year, there have been key advances in our understanding of arrhythmia mechanisms and diagnosis and important new therapies. We have seen advances in basic cardiac electrophysiology with demonstration of optogenetic targeting of atrial fibrillation (AF) rotors, induced pluripotent stem cell-based biological pacemakers, small-conductance Ca 2+ -activated K + (SK) channels as targets for AF treatment, and reductions in inward rectifier potassium current in promoting ventricular fibrillation. Hand-held ECG devices and implantable loop recorders have been shown to detect subclinical AF. Catheter ablation of AF in patients with left ventricular dysfunction improves outcomes compared with medical therapy. Both hybrid thoracoscopic surgical and catheter ablation procedures and off-pump surgery for AF have demonstrated efficacy. Anticoagulation with uninterrupted dabigatran had a lower major bleeding rate compared with uninterrupted warfarin after AF ablation. Studies have examined optimizing access to automatic external defibrillators by identifying optimal locations for placement and possibility of using a drone delivery network. In long-QT syndrome, there are advances in understanding of ECG predictors of arrhythmic events, the role of the role of gene variants in conferring arrhythmic risk, and effect of age and sex on QTc interval. There are numerous advances in the treatment of ventricular tachycardia, including noninvasive cardiac radiation. Catheter ablation and implantable devices continue to demonstrate effectiveness in patients with congenital heart disease.In the past year, there have been numerous ground-breaking discoveries and observations that illustrate the vibrancy and promise of our field. In this review, we have tried to capture articles published in the year 2017 of particular interest to cardiac electrophysiologists. Although we have focused on articles from our journal, we have captured many of the most impactful articles in numerous other journals. We apologize for omitting a large number of other important articles that cannot be included in this review because of space limitations. We have placed some of these in our Data Supplement. BASIC ELECTROPHYSIOLOGY BradyarrhythmiasThe search for new biological therapies for bradycardia met with recent progress as human keratinocytes genetically reprogrammed into electrically unstable cardiomyocytes were shown to persist and provide continued catecholaminergic-responsive pacing for 13 weeks after subepicardial injection into immunosuppressed dogs at the time of atrioventricular (AV) node ablation.1 Although only 40% to 80% of the beats matched the site of cell injection, this is first study to test a human induced pluripotent stem cell-based biological pacemaker in a large animal model of heart block and represents an important step forward in biological pacing.

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Genetic Obesity and the Risk of Atrial Fibrillation

Cited by 99 publications

References 72 publications

Differences in Epidemiology and Risk Factors for Atrial Fibrillation Between Women and Men

Differences in Epidemiology and Risk Factors for Atrial Fibrillation Between Women and Men

No evidence of a causal association of type 2 diabetes and glucose metabolism with atrial fibrillation

Year in Review in Cardiac Electrophysiology

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