Weight loss combined with close management of hypertension and other risk factors results in fewer atrial fibrillation (AF) events and less symptom burden in highly symptomatic patients with AF vs risk factor management alone, a new study shows.
The new findings are important because no previous studies have shown that risk factor management has a beneficial effect on AF, and so current guidelines don't include this approach, said study author Prashanthan Sanders, PhD, professor, cardiology, and director, Center of Heart Rhythm Disorders, University of Adelaide, Australia.
"Weight and risk factor management should be a normal part of managing a person with atrial fibrillation," he told Medscape Medical News. Along with obesity and hypertension, diabetes mellitus and obstructive sleep apnea are other independent risk markers for AF.
The study was published in the November 20 Cardiology/Cardiovascular Disease–themed issue of JAMA.
The study initially aimed to look at the effect of weight loss alone on AF. "Our community is getting heavier and the incidence of atrial fibrillation is going up. We had a previous animal study that showed that when we overfed animals they got AF," explained Dr. Sanders. AF has been described as "the epidemic of the new millennium," with projections for up to 15 million Americans expected to be affected by 2050, he said.
But it's impossible to separate out obesity from related risk factors. "When a human loses weight, their diabetes improves, their sleep apnea seems to go away, and their hypertension goes away," said Dr. Sanders. "So the study evolved to one of treating weight and risk factors."
This single-center trial included 150 adult patients with symptomatic paroxysmal or persistent AF, a body mass index (BMI) greater than 27 kg/m2, and a waist circumference more than 100 cm for men and 90 cm for women. These patients were randomly assigned to a control or an intervention group.
The controls (n = 75) received exercise advice and fish oil if they weren't taking dual antiplatelet agents or oral anticoagulants. They also completed diet and activity diaries.
Those in the intervention group (n = 75) followed a target-driven very-low-calorie diet, which was gradually replaced after 8 weeks with low-glycemic-index meals. These patients were also prescribed low-intensity exercise (walking or cycling) for 20 minutes 3 times a week, which was later increased to 45 minutes 3 times weekly. They also had goal-directed face-to-face clinic visits every 3 months.
The primary outcome was AF symptom burden, quantified using the Atrial Fibrillation Severity Scale (AFSS), which captures AF frequency, duration, and severity. A score on this validated scale can range from 3.25 (single, minimally symptomatic episode lasting only minutes) to 30 (continuous, highly symptomatic episode lasting more than 48 hours).
In both groups, researchers managed hypertension, hyperlipidemia, glucose intolerance, sleep apnea, and alcohol and tobacco use. Patients were prescribed antiarrhythmic agents for rate control, rhythm control, or both.
Researchers obtained Holter recordings at baseline and at 12 months, with any episode of AF lasting 30 seconds or longer considered AF. They also measured left atrial area and left ventricular wall thickness from transthoracic echocardiography.
After a mean follow-up of 15 months, both groups had lost weight, but the intervention group lost significantly more (14.3 kg vs 3.6 kg [32 vs 8 lbs]; P < .001).
Compared with the control group, those in the intervention group had a significantly greater reduction in AFSS symptom burden scores. The analysis also showed significantly greater decline among the intervention group for scores on AF episodic frequency, episode duration, and global episode severity.
Table. Change in AF Burden by Treatment Endpoint
Intervention Control P Value
AFSS symptom burden score (points)11.82.6<.001
AF episodic frequency3.40.7<.001
AF episode duration5.00.8<.001
AF global episode severity8.41.7<.001
The 7-day continuous ambulatory rhythm recordings showed that the number of episodes dropped from 3.3 to 0.62 in the intervention group but changed much less in the control group (from 2.8 to 2.0). In addition, the cumulative duration of episodes dropped from 1176 to 491 minutes in the treatment group but increased from 1394 to 1546 minutes in the control group.
Interventricular septal thickness decreased in both groups (1.1 mm in the treatment group and 0.6 mm in the control group; P = .02), as did the left atrial area (3.5 and 1.9 cm2, respectively; P = .02).
Use of metformin, hypolipidemic agents, and continuous positive airway pressure (a treatment for sleep apnea) increased in both the intervention and control groups. The number of patients with elevated blood pressure and elevated lipid levels decreased in both groups.
Although epidemiologic data suggest a 4% to 5% increased risk of developing AF with each 1-unit increase in BMI, there's no concrete indication of how much the risk is reduced for every incremental decrease in BMI. However, from his own patient observations, Dr. Sanders estimated that the threshold may be at a 10% reduction in body weight.
That target should become clearer in the near future, he added. "Probably in a year's time we will have at least 500 people going through the program and we may be able to draw a curve and say here's the threshold."
Excessive alcohol consumption, another modifiable risk factor for AF, decreased more in the intervention group.
There's no concrete upper limit for alcohol consumption, although a study cited in this new paper estimated the risk at 8% per 10-g daily consumption increment. On the basis of his own clinical practice, Dr. Sanders said that limiting alcohol consumption to 30 g a week is probably a good recommendation.
"Hopefully, we will have 3 or 4 follow-up studies that will come out soon which will reinforce the 30-gram target," he said.
In the current study, systolic and diastolic blood pressure decreased in the intervention group but changed little in the control group. Use of antihypertensive agents decreased in the intervention group and increased in the control group (hypertension increases the risk for AF by an estimated 70% to 80%, according to the authors).
Diabetes, another risk factor, has been shown to increase the risk for new-onset AF by 50%. In this study, patients in the intervention group experienced a 60% reduction in serum insulin levels and a 48% reduction in serum C-reactive protein levels, which could be expected with weight loss.
Current treatment guidelines don't yet include risk management for the treatment of AF because "no one has ever proven it before," stressed Dr. Sanders. "That's the message that needs to get out; you need to manage your risk factors," he said.
A limitation of the study was the number of dropouts, due to the need for another intervention, lack of motivation to lose weight, or loss to follow-up. However, according to the authors, a sensitivity analysis showed that the findings in favor of the intervention group "are robust, even in the face of imbalanced participant dropout."
Another limitation was that the study was not completely blinded. The physicians overseeing the weight loss program and the patients themselves could not be blinded (although participants were told not to disclose their status).
Approached for comment, Torben Bjerregaard Larsen, MD, PhD, Department of Cardiology, Aalborg University Hospital, Denmark, said the study's finding "can have important implications for future rehabilitation programs" for patients with AF.
"This study can even have further implications, especially seen from a neurologist's perspective," Dr. Larsen told Medscape Medical News. He noted that a large observational study from Denmark demonstrated that both overweight and obesity, as determined by BMI, are associated with a significantly higher risk for ischemic stroke, thromboembolism, and/or death among patients with AF.
Although the prognostic impact of obesity on outcomes among patients with AF "is sparsely investigated," a recent systematic review found that moderate-intensity physical activity improved exercise capacity, quality of life, and the ability to carry out activities of daily living among patients with AF, said Dr. Larsen.
More studies that can improve rehabilitation programs in patients living with AF "are highly warranted," he said.
The study was sponsored by the University of Adelaide. Dr. Sanders reports being supported by the National Heart Foundation of Australia (NHFA) and by a Practitioner Fellowship from the National Health and Medical Research Council (NHMRC); serving on the advisory boards of Biosense-Webster, Medtronic, St Jude Medical, sanofi-aventis, and Merck Sharpe & Dohme; receiving lecture and/or consulting fees from Biosense-Webster, Medtronic, St Jude Medical, Boston Scientific, Merck Sharpe & Dohme, Biotronik, and sanofi-aventis; and receiving research funding from Medtronic, St Jude Medical, Boston Scientific, Biotronik, and Sorin.
JAMA. 2013;310:2050-2060. Abstract