The Association Between Diabetes Mellitus and Atrial Fibrillation: Clinical and Mechanistic Insights

To determine the independent risk factors for atrial fibrillation. Cohort study. The Framingham Heart Study. A total of 2090 men and 2641 women members of the original cohort, free of a history of atrial fibrillation, between the ages of 55 and 94 years. Sex-specific multiple logistic regression models to identify independent risk factors for atrial fibrillation, including age, smoking, diabetes, electrocardiographic left ventricular hypertrophy, hypertension, myocardial infarction, congestive heart failure, and valve disease. During up to 38 years of follow-up, 264 men and 298 women developed atrial fibrillation. After adjusting for age and other risk factors for atrial fibrillation, men had a 1.5 times greater risk of developing atrial fibrillation than women. In the full multivariable model, the odds ratio (OR) of atrial fibrillation for each decade of advancing age was 2.1 for men and 2.2 for women (P < .0001). In addition, after multivariable adjustment, diabetes (OR, 1.4 for men and 1.6 for women), hypertension (OR, 1.5 for men and 1.4 for women), congestive heart failure (OR, 4.5 for men and 5.9 for women), and valve disease (OR, 1.8 for men and 3.4 for women) were significantly associated with risk for atrial fibrillation in both sexes. Myocardial infarction (OR, 1.4) was significantly associated with the development of atrial fibrillation in men. Women were significantly more likely than men to have valvular heart disease as a risk factor for atrial fibrillation. The multivariable models were largely unchanged after eliminating subjects with valvular heart disease. In addition to intrinsic cardiac causes such as valve disease and congestive heart failure, risk factors for cardiovascular disease also predispose to atrial fibrillation. Modification of risk factors for cardiovascular disease may have the added benefit of diminishing the incidence of atrial fibrillation.

The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established that advanced age, male sex, and European ancestry are prominent AF risk factors. Other modifiable risk factors include sedentary lifestyle, smoking, obesity, diabetes mellitus, obstructive sleep apnea, and elevated blood pressure predispose to AF, and each factor has been shown to induce structural and electric remodeling of the atria. Both heart failure and myocardial infarction increase risk of AF and vice versa creating a feed-forward loop that increases mortality. Other cardiovascular outcomes attributed to AF, including stroke and thromboembolism, are well established, and epidemiology studies have championed therapeutics that mitigate these adverse outcomes. However, the role of anticoagulation for preventing dementia attributed to AF is less established. Our review is a comprehensive examination of the epidemiological data associating unmodifiable and modifiable risk factors for AF and of the pathophysiological evidence supporting the mechanistic link between each risk factor and AF genesis. Our review also critically examines the epidemiological data on clinical outcomes attributed to AF and summarizes current evidence linking each outcome with AF.

Atrial fibrillation is a common arrhythmia associated with increased cardiovascular morbidity and mortality. This study was undertaken to identify the natural history of this condition, including risk factors for its development, and outcome. The incidence of atrial fibrillation among 3,983 male air crew recruits observed continuously for 44 years was calculated based on person-years of observation. Age and 23 variables were examined to identify risk factors for atrial fibrillation. Controlling for age and 9 prognostic variables, the effect of atrial fibrillation on 8 outcomes was examined. Analysis of risk factors for atrial fibrillation and outcome after atrial fibrillation was based on a Cox proportional hazard model using time-dependent covariates. Of the 3,983 study members, 299 (7.5%) developed atrial fibrillation during 154,131 person-years of observation. The incidence rose with age from less than 0.5 per 1,000 person-years before age 50 to 9.7 per 1,000 person-years after age 70. Risk for atrial fibrillation was increased with myocardial infarction (relative risk [RR] 3.62), angina (RR 2.84), and ST-T wave abnormalities in the absence of ischemic heart disease (RR 2.21). The RR for atrial fibrillation was strongest at the onset of ischemic heart disease and diminished over time. The rate of atrial fibrillation was 1.42 times increased in men with a history of hypertension. Congestive heart failure, valvular heart disease, and cardiomyopathy were important but uncommon risk factors. Atrial fibrillation independently increased the risk for stroke (RR 2.07) and congestive heart failure (RR 2.98). Total mortality rate was increased 1.31 times; cardiovascular mortality including and excluding fatal stroke were also increased (RR 1.41 and 1.37, respectively). The incidence of atrial fibrillation in men increases with advancing age. Clinical cardiac abnormalities, particularly recent ischemic heart disease and hypertension, are strongly associated with increased risk for atrial fibrillation. Atrial fibrillation increases morbidity and mortality, but the magnitude of the increase may be less than previously reported.