Are body mass index changes related to incident atrial fibrillation?—Results of the Danish Diet, Cancer, and Health Cohort

This editorial refers to ‘Five-year changes in weight and risk of atrial fibrillation in the Danish Diet, Cancer, and Health Cohort’, by T.C. Frederiksen et al., https://doi.org/10.1093/eurjpc/zwad300. Atrial fibrillation (AF) prevalence is significantly rising worldwide, with over 33 million prevalent cases and 5 million incident cases.1,2 Experts predict these numbers will triple over the next three decades, leading to AF being labelled as an epidemic.1,3 This has been worsened by the increasing burden of modifiable cardiovascular risk factors such as hypertension, increased body mass index (BMI), alcohol consumption, and smoking.1,3 Obesity, defined as BMI ≥30 kg/m2 in population-based studies, is another epidemic within itself and a major contributor to the rising AF burden, linked to a nearly two-fold risk of future AF risk.3 Likewise, a recent meta-analysis reported that for every 5-unit increase in BMI, there was an increase in incident AF of about 20–30%.1–3 From the pathophysiological standpoint, obesity triggers, and contributes to AF development, burden, progression, and symptom severity while increasing the prevalence of poor outcomes and recurrence after treatment (e.g. ablation).1,2 The pathways that lead to AF in those with increased BMI are not entirely understood; however, mechanisms are thought to be multifactorial, direct or indirect and can be summarized as follows: (i) compensatory haemodynamic changes in response to increased circulating volume and additional perfusion needs as a consequence of excessive adipose tissue deposition;4 (ii) epicardial adipose tissue, doubling AF risk regardless of body composition or fat distribution,5 (iii) conduction system abnormalities as consequence adipose and fibrotic atrial remodelling,2,4 and (iv) through disease mechanisms caused by conditions associated with obesity, like systemic hypertension, obstructive sleep apnoea, and coronary artery disease.1,4 The study by Frederiksen et al.6 published in this issue was motivated by the inconclusive results in the literature regarding weight reduction and the risk for AF.1,4 The authors followed 43 758 adults aged 50–64 without known AF at baseline, from the Danish Diet, Cancer, and Health Cohort, a large population-based study for over 15.7 years. They analysed the association between 5-year weight changes vs. stable weight, and risk for incident AF; individuals underwent anthropometric evaluation by trained personnel at the first evaluation; consequently, after a 5-year time period, anthropometric information was collected through phone encounters. The authors compared those with stable weight vs. those with weight changes based on the direction of variation (e.g. weight gained or loss) and the magnitude based on BMI change (e.g. 2.5–5 kg/m2 or ≥5 kg/m2). Authors report two main findings: First, and in line with large prospective cohort studies, there was a dose–response association between the degree of weight gain and incident AF, showing a two-fold increased risk for AF in subjects gaining five or more units of BMI, with similar results in stratified analysis and in those considered overweight or obese by BMI. Those results were comparable to the Women’s Health Study (WHS) with a 41% increased risk in those who became obese as defined by BMI after follow-up [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.05–1.90],1 the Nord-Trøndelag Health Study-3 (HUNT-3) study were an increase BMI > 5 kg/m2 represented over two-fold risk for AF (HR 2.6, 95% CI 1.3–5.2).2 Additionally, in a Korean nationwide cohort study where average successive variability of BMI was evaluated over 4 years, those who reported increased variability in body weight had 32% more probability of incident AF (HR 1.32, 95% CI 1.01–1.71);7 highlighting the effect of variability of body weight and BMI in the incidence of AF. The second main finding in the study by Frederiksen et al.6 is that weight loss was not associated with a lower risk of incident AF. This finding could be seen as unexpected considering the mechanisms linking obesity and AF, as well as the reduction in AF burden following lifestyle interventions that included weight loss in clinical trials.8,9 A key factor in explaining the seemingly unexpected results is whether the weight loss was intentional or unintentional. As the authors pointed out, other observational studies have shown similar results, and even paradoxical results, with a higher incidence of AF in individuals losing weight, like in the WHS.1 Those negative or paradoxical findings could be explained by confounding factors, especially if weight loss was unintentional in some or many subjects in those cohorts losing weight. Unfortunately, the intentionality of weight loss was not assessed in any of those studies. For those reasons, the observation that weight loss was not associated with lower rates of AF should not affect the recommendation to lose weight in people at risk for AF or with paroxysmal AF. There is abundant experimental evidence coming from randomized studies that lifestyle modification, including weight loss, reduces AF burden, and may prevent AF episodes.1,2 There is also evidence from studies where subjects who achieved significant weight loss through bariatric surgery or using pharmacologic therapies had lower AF rates.2,8 And finally, we need to recognize that the benefits of weight loss go beyond AF prevention and may impact many other aspects of health, like preventing or controlling obstructive sleep apnoea, heart failure with preserved ejection fraction, and glucose metabolism, among many other benefits of weight loss. Frederiksen et al.6 performed an observational study with major advantages, and some limitations are worth mentioning. Body mass index was the unit of measure of weight change, and although widely used in epidemiological studies, changes in BMI do not fully reflect changes in body composition and fat distribution.10,11 Weight was self-reported, something that may induce bias, and the cohort age distribution was limited, which may limit the generalizability of the results. Thus, the results of this and other studies serve as evidence to support the optimization of lifestyle to prevent weight gain as a way to prevent AF, and underscore the need for randomized trials when it comes to conclusions related to the effects of weight loss to prevent AF.12 The authors received no financial support for the research, authorship, and/or publication of this article. No new data were generated or analysed in support of this research.