Genetically-determined body mass index and the risk of atrial fibrillation progression in men and women.

J E Siland,B O Nguyen,M Rienstra,P Van Der Harst,R R De With,I C Van Gelder

doi:10.1371/journal.pone.0246907

J E Siland, B O Nguyen + Show 4 more

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https://doi.org/10.1371/journal.pone.0246907

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Abstract

AimsLimited causal evidence is available on the relationship between body mass index (BMI) and atrial fibrillation (AF) progression. Sex differences have been noted and may be relevant for AF progression. We investigated the association between the BMI Genetic Risk Score (GRS) and AF progression in men and women of the Groningen Genetic Atrial Fibrillation (GGAF) cohort.Methods and resultsThe GGAF cohort (n = 2207) is a composite of 5 prospective cohorts with individuals of European ancestry. AF patients with genetic information, with at least 12 months follow-up and AF progression data were included. AF progression was defined as progression from paroxysmal to persistent/permanent AF, or persistent to permanent AF. A BMI GRS was constructed of genetic variants associated with BMI. Univariate and multivariate Cox proportional hazard regression analyses were performed in the total population and in men and women, separately. During a median follow-up of 34 [interquartile range 19–48] months 630 AF patients (mean age 62±11, 36% women, BMI of 28±5) were analyzed, and men and women developed similar AF progression rates (respectively 6.5% versus 6.1%). The BMI GRS was not associated with AF progression either as a continuous variable or in tertiles in the overall population. However, the BMI GRS was associated with the tertile of the highest BMI GRS in women (n = 225), also after multivariable adjustments of clinical risk factors (Hazard ratio 2.611 (95% confidence interval 1.151–5.924) p = 0.022).ConclusionsGenetically-determined BMI is only associated with women at risk of AF progression. The results may be supporting evidence for a causal link between observed BMI and AF progression in women. We emphasize the need for further investigation of genetically determined BMI and observed BMI to optimize AF management in women with increased risk for AF progression.

Highlights

Obesity and atrial fibrillation (AF) are both emerging global epidemics and causing a growing economic burden [1]
Genetically-determined body mass index (BMI) is only associated with women at risk of AF progression
Of the 2207 individuals included in the Groningen Genetic Atrial Fibrillation (GGAF) cohort, we included 630 AF patients with shortlasting paroxysmal or persistent AF in present analysis (Fig 1)

Summary

Introduction

Obesity and atrial fibrillation (AF) are both emerging global epidemics and causing a growing economic burden [1]. AF is associated with an increased risk of cardiovascular diseases like heart failure, stroke, dementia and death [1]. When AF progresses from paroxysmal / self-limiting to more sustained / non-self-limiting forms of AF, more cardiovascular events occur [2]. In an attempt to unravel the development of AF progression, several risk factors were identified. Higher observed body mass index (BMI) has been associated with an increased risk of AF. The association between observed BMI and the risk of incident AF differed between men and women [3, 4]. It is possible that sex is a modifying factor in the relation between increased observed BMI and development or AF progression

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