Obesity and AF: mechanisms and treatment options

Nikhil Ahluwalia -

Even though we've spoken about the cardioprotective effects of exercise, does obesity have a pro-arrhythmic effect? The answer simply is yes. Obesity is an independent risk factor for AF. Being overweight/obese counted for 17.9% of all AF cases in the analysis of a large American observational study, the Atherosclerosis Risk in Communities (ARIC) study. The risk of AF increases linearly with body mass index (BMI), making obesity the second biggest attributable risk factor for AF after hypertension. The Framingham Heart Study (a long-term, multi-generational, observational study of a community) suggests that every unit increase in BMI correlated with a 4–5% increase in AF risk.

As the global prevalence of obesity continues to rise, it has become increasingly important to understand how it influences the risk of AF. Studies have shown that weight reduction can lead to a significant decrease in the recurrence of AF, underscoring the importance of addressing obesity as part of a comprehensive approach to managing and preventing AF.

The underlying pathophysiological mechanisms linking excess weight and AF are poorly understood but may be related to left ventricular hypertrophy, diastolic dysfunction, left atrial dilatation, increased atrial fibrosis and epicardial adipose tissue. In addition, obesity is an independent risk factor for other cardiovascular diseases (e.g. hypertension, coronary artery disease, metabolic syndrome) that in turn increase the risk of AF. Another important condition that correlates excess weight with AF is obstructive sleep apnoea which is more common in obesity and increases the risk of AF by 4-fold.

AF-related outcomes associated with obesity. Image adapted from here.

Obesity contributes to other conditions that can further exacerbate AF. For example, obesity is associated with an increased risk of sleep apnoea, which has been shown to independently increase the risk of AF. Moreover, obesity can coexist with other cardiovascular risk factors, such as hypertension, diabetes, and dyslipidemia, all of which can increase the likelihood of developing AF as well.

Obesity is associated with various haemodynamic changes that can alter cardiac structure and physiology, ultimately leading to an increased risk of AF. For instance, adiposity typically results in an increase in total blood volume, which in turn raises cardiac output. A sustained rise in cardiac output can cause left ventricular enlargement and hypertrophy. Over time, these changes can lead to diastolic dysfunction and eventually systolic impairment, both of which contribute to the development and maintenance of AF.

Furthermore, obesity can promote atrial remodeling, a process characterized by structural and electrical changes in the atrial myocardium that make it more susceptible to AF. Atrial remodeling can result from increased atrial pressure, oxidative stress, and inflammation, all of which are more likely to occur in individuals with obesity.

Epicardial Adipose Tissue (EAT):

Animal studies and imaging work have suggested this relationship may be mediated by increased fat deposits surrounding the heart and releasing 'pro-AF' hormones and chemicals that drive the disease progression. This is known as epicardial adipose tissue

Cross-sectional imaging data has shown that EAT volume correlates with an increased risk of AF, particularly left atrial EAT volume. EAT is a highly active visceral tissue that produces various pro- and anti-inflammatory adipocytokines, metabolic and growth factors, which can directly diffuse into the myocardium. Local inflammation, driven by these factors, is believed to play a key role in the development of AF.

The production of inflammatory cytokines and other molecules by EAT can lead to fibrosis and electrical remodeling of the atrial myocardium, increasing the vulnerability to AF.

Weight loss

A compelling paper from an Australian group in 2021 showed a potential reversal of the AF disease pathway with weight reduction. (Reference below). Albeit, in sheep, weight increases negatively affected the shape, stiffness and fattiness of the left atrium in ways associated with AF and weight loss reversed these.

Lifestyle management is a hot area for AF research in 2022 and you're likely to see more work coming out in this area in the coming years. The International guidelines advocate lifestyle interventions like weight management as a first-line pillar in AF prevention and treatment and so if you have AF and you haven't discussed lifestyle factors with your medical team yet- please do!

Ozempic and AF

Ozempic is the 'celebrity weightloss drug' that has been licensed for years in the treatment of diabetes. However, it has been in the headlines this year as the effect of Ozempic (the trade name for Semaglutide) as it has been shown to dramatically led to weight loss in non-diabetics also. Let's put the moral question of whether we should medicalise obesity or offer drugs to treat it (Ozempic isn't licensed yet for this purpose alone in the UK) to one side for the moment. If Ozempic leads to weight loss and weight loss can reduce the AF burden, how does Ozempic effect AF control? Interestingly the manufacturers launched a study of this in 2022 but chose to suspend it for reasons I could not find according to their post on clinicaltrials.org. So we'll probably have to wait several years to formally know the answer to this question.

Mahajan R, Lau DH, Brooks AG, Shipp NJ, Wood JPM, Manavis J, Samuel CS, Patel KP, Finnie JW, Alasady M, Kalman JM, Sanders P. Atrial Fibrillation and Obesity: Reverse Remodeling of Atrial Substrate With Weight Reduction. JACC Clin Electrophysiol. 2021 May;7(5):630-641. doi: 10.1016/j.jacep.2020.11.015. Epub 2021 Feb 24. PMID: 33640353.

Vyas V, Lambiase P. Obesity and Atrial Fibrillation: Epidemiology, Pathophysiology and Novel Therapeutic Opportunities. Arrhythm Electrophysiol Rev. 2019 Mar;8(1):28-36. doi: 10.15420/aer.2018.76.2. PMID: 30918664; PMCID: PMC6434511.