Obesity Paradox in Atrial Fibrillation: Implications for Outcomes and Relationship With Oral Anticoagulant Drugs

Marco Proietti; Giuseppe Boriani


Am J Cardiovasc Drugs. 2020;20(2):125-137. 

In This Article

Relationship Between Obesity and Atrial Fibrillation (AF)

As mentioned, in 2008, Wanahita et al.[8] conducted a meta-analysis including 123,249 patients and reported that the presence of obesity was associated with an increased risk of AF (risk ratio (RR) 1.08; 95% confidence interval (CI) 1.04–1.12). In particular, they found that, in the population-based cohort studies subgroup, being obese increased the risk of having AF by almost 50%, whereas the increase in risk was not significant (RR 1.02; 95% CI 0.99–1.06) in the post-cardiac surgery subgroup. Importantly, the authors demonstrated that being obese conferred a higher risk than being overweight.[8] A larger meta-analysis including 626,603 patients highlighted that, beyond the general population, being obese increased the risk of developing AF in the post-cardiac surgery clinical setting (10% risk increase) and the risk of recurrent AF in patients receiving an ablation procedure (13% risk increase).[12] A more recent meta-analysis investigating the relationship between continuous BMI and the risk of AF showed that an increase in 5 BMI units was associated with a 28% increase in the relative risk of presenting with AF.[13] It also showed that the increased AF risk was progressively higher with increasing BMI, with a nonlinear relationship, with an increase in risk starting even from a BMI of 23 and with a clear exposure–effect relationship between BMI and the risk of AF.[13] Additionally, the ARIC (Atherosclerosis Risk in Communities) study found that one in five AF cases could be directly attributable to overweight and obesity.[14]

Several reasons and mechanisms have been identified as possibly responsible for this strong link between the two conditions. On one hand, the presence of obesity independently increased the risk of developing several different conditions (i.e., hypertension, diabetes, heart failure), which themselves increased the risk of developing AF. This not-withstanding, the direct relationship between obesity and AF has been shown to persist even after multivariate adjustments.[6] On the other hand, obese patients have been found to present with a number of modifications in physiology and morphology of the heart that can directly cause heart failure[15] and AF.[6] Indeed, the impact of obesity in determining changes to hemodynamics (i.e., increased blood volume, stroke volume, arterial pressure), cardiac structure (i.e., left ventricular concentric remodeling and hypertrophy, right ventricular hypertrophy, atrial enlargement) and cardiac function (i.e., left ventricular diastolic and systolic dysfunction and right ventricular dysfunction) have been reported among factors influencing AF occurrence.[6] In fact, the presence of conduction abnormalities, fractionated electrograms and increased profibrotic status directly connected to increased vulnerability to AF have been demonstrated.[16] Furthermore, the presence of increased pericardial fat can induce a paracrine pro-inflammatory status (with increased interleukin-1-β and tumor necrosis factor-α) that, beyond the cardiac structural changes already mentioned, may lead to the onset of AF.[17]

The reduced AF risk observed in patients receiving specific interventions to reduce their weight further strengthens the relationship between obesity and AF.[5] In the LEGACY study, 355 obese patients with AF who underwent an ablation procedure were managed with an integrated approach (counseling; meal and exercise plans) to obtain a significant weight reduction over a 5-year follow-up.[18] This study showed that long-term weight loss and linear weight reduction (avoiding weight fluctuations) significantly reduced the occurrence of recurrent AF.[18] Moreover, the reduction in AF risk was greatest when weight loss was associated with significant improvements in cardiorespiratory fitness.[19] All these data in combination led several researchers to postulate a causative link between obesity and AF (Figure 1).

Figure 1.

The causative link between obesity and atrial fibrillation. AF atrial fibrillation