Obesity and Atrial Fibrillation: Title and subTitle BreakIs One Epidemic Feeding the Other?

Obesity has reached epidemic proportions in the United States; nearly 65% of the population is overweight and nearly 31% is obese.¹ Similarly, atrial fibrillation (AF) is reaching epidemic proportions,² with nearly 2.5 million Americans currently affected. As the population ages, it is estimated that by the year 2050 more than 5 million Americans will have AF.³ Obesity is clearly associated with increased prevalence of hypertension, coronary artery disease, diabetes mellitus, left ventricular hypertrophy, left atrial enlargement, and congestive heart failure.^{4 - 5} In turn, hypertension, left atrial enlargement, and congestive heart failure are all thought to be important contributors to the development of AF.^{3 ,6} Recently, obstructive sleep apnea, which occurs in about 40% of obese individuals, has been found to be strongly associated with AF.⁷ Despite these biological links, a clear association between obesity and risk of AF has not been established.

In this issue of JAMA, Wang and colleagues⁸ studied the relationship between obesity and subsequent development of AF in the Framingham Heart Study using body mass index (BMI) as a surrogate for obesity. The Framingham group⁵ has already reported on a strong link between obesity and development of heart failure. In the current study, they report a progressive increase in the risk of developing AF as BMI, measured as weight in kilograms divided by the square of height in meters, increased from normal (<25) to overweight (25 to <30) to obese (≥30). In a multivariable model adjusted for cardiovascular disease risk factors and the occurrence of interim myocardial infarction or heart failure, every 1-unit increment in BMI was associated with a 4% increase in risk of AF in both men and women. When the authors compared the risk for obese individuals with that for normal-weight individuals, obesity was correlated with a 50% increased risk, also irrespective of sex.

The authors also observed a graded increase in left atrial size as BMI category increased from normal to overweight to obese, consistent with previous observations establishing obesity as a major risk factor for the development of left atrial enlargement.^{4 ,9} After adjusting for left atrial diameter, obesity was no longer associated with an increased risk for the development of AF, whereas left atrial diameter remained strongly associated with risk of AF. These findings suggest a possible physiological link between obesity and AF. Left atrial remodeling is an established mechanistically important factor in the pathogenesis of AF, whether by increasing left atrial size, by allowing for the occurrence of a critical number of reentrant wavelets, or by left atrial stretch, triggering pulmonary vein foci.^{10 - 11} Left atrial enlargement is usually secondary to increases in left ventricular end-diastolic pressure (hypertension, increased left ventricular mass, cardiomyopathy, congestive heart failure) or mitral valve pathology. Some controversy still exists as to whether increased left ventricular mass is a prime determinant of left atrial enlargement in obesity.^{4 ,9}

Although the magnitude of the association of obesity with risk of developing AF is seemingly modest (4% increased risk for each additional unit in BMI), the public health implications of this observation are substantial because obesity is a potentially modifiable risk factor and because AF is strongly correlated with increased risk of stroke and death.³

It is noteworthy that when BMI was considered as a dichotomous variable, obese individuals—but not those who are overweight—demonstrated a statistically significant increase in risk of AF. This raises the possibility of a threshold effect. However, when the authors excluded individuals with frank obesity, the association between increasing BMI and AF persisted. This suggests that even mild improvements in population BMI may lead to substantial reductions of disease burden related to AF.

This association between BMI and the risk of AF remained after correcting for age, sex, and hypertension. However, the prevalence of hypertension and advanced age was low in this population-based cohort, and it remains possible that the arrhythmogenic effects of obesity are mediated via age and/or hypertension, both of which could also lead to left atrial enlargement. In a previous report from the Framingham study, obesity was not a risk factor for the development of AF.⁶ In that report, the prevalence of hypertension, left ventricular hypertrophy, and congestive heart failure was higher than in the current cohort. It also appears that the cohort reported in 1994 had a lower prevalence of elevated BMI, whereas the current cohort has a prevalence of overweight and obesity that mirrors that of the general population.

From a public health perspective, older age is clearly the most important risk factor for the development of AF.⁶ With advancing age there is also increased fibrosis in the atria, which leads to side-to-side uncoupling of myocardial fiber bundles and development of nonuniform anisotropy, ultimately leading to a substrate for reentrant excitation and AF.¹² Another potential mechanism by which obesity may lead to the development of AF is obstructive sleep apnea, which predisposes to a number of arrhythmogenic events, including hypoxia, hypercapnea, increased sympathetic tone, and transient atrial dilatation.⁷ In the current study, atrial flutter comprised 9% of the incident arrhythmias. This is interesting because of the link between cor pulmonale and atrial flutter. Also, since AF was diagnosed if it was documented on a single electrocardiogram, it is possible that some of the episodes of AF started as atrial flutter.

The study by Wang et al is important and timely, given the epidemic proportions of both obesity and AF. Obesity now needs to be considered a risk factor for the development of AF. Although the increased risk for the development of AF with increased BMI is modest, the public health implications are substantive. Atrial fibrillation is responsible for a 3- to 5-fold increased risk of stroke and a 2-fold increased risk of mortality, and it is reaching epidemic proportions as the US population ages.³ Certainly, the adverse consequences of obesity are well documented and are behind major public health initiatives aimed at lifestyle modification, including exercise and diet. Now it seems that these life style modifications also may have an impact on the epidemic of AF and the morbidity and mortality associated with that condition.